MED1 HISTO Nerve Tissue PDF

Histology LECTURE 1ST SEMESTER FINALS NERVE TISSUE OVERVIEW OF THE NERVOUS SYSTEM THE NERVOUS SYSTEM ALLOWS RAPID RESPONSE TO EXTER...

Histology LECTURE 1ST SEMESTER FINALS NERVE TISSUE OVERVIEW OF THE NERVOUS SYSTEM THE NERVOUS SYSTEM ALLOWS RAPID RESPONSE TO EXTERNAL The nervous system enables the body to respond to STIMULI. changes in its external and internal environment and integrates organ system activities. The nervous system evolved from simple neuroeffector Anatomically, the nervous system is divided into: systems in invertebrates. Primitive nervous systems have simple receptor–effector Central nervous Brain and spinal cord. reflex loops. system (CNS) In higher animals and humans, the SNS responds to Peripheral nervous Cranial, spinal, and peripheral external stimuli via effector cells (e.g., skeletal muscle). system (PNS) nerves, ganglia, and specialized Neuronal responses in higher animals are more varied, nerve endings. from simple reflexes to complex brain functions like Neural pathways, including reflex arcs, mediate reflex memory and learning. actions. Most sensory neurons communicate with motor THE AUTONOMIC PART OF THE NERVOUS SYSTEM REGULATES THE neurons in the spinal cord. FUNCTION OF INTERNAL ORGANS Functionally, the nervous system is divided into: Effectors in internal organs that respond to autonomic neurons: Somatic nervous system (SNS): Controls voluntary Smooth muscle Contraction modifies the functions (except reflex arcs), provides sensory and motor diameter or shape of organs innervation to all body parts except viscera, smooth and like blood vessels, gut, cardiac muscle, and glands. gallbladder, and bladder. Autonomic nervous system (ANS): Provides involuntary Cardiac conducting Regulate cardiac muscle motor innervation to smooth muscle, heart conducting cells (Purkinje contraction rate, modified by system, and glands; provides afferent sensory innervation fibers) autonomic impulses. from viscera. Glandular Regulates synthesis, ANS is further divided into sympathetic, parasympathetic, epithelium composition, and release of and enteric divisions. secretions. Enteric division serves the alimentary canal and communicates with the CNS but can function Regulation of internal organs involves cooperation independently. between the nervous and endocrine systems. Neuroendocrine tissue: Neurons in the brain and other COMPOSITION OF NERVE TISSUE sites act as secretory cells. Neurosecretions regulate functions in endocrine, digestive, NERVE TISSUE CONSISTS OF TWO PRINCIPAL TYPES OF CELLS: respiratory, urinary, and reproductive systems. NEURONS AND SUPPORTING CELLS THE NEURON Neuron is the functional unit of the nervous system, with a cell body and processes. THE NEURON IS THE STRUCTURAL AND FUNCTIONAL UNIT OF THE Neurons receive stimuli and conduct impulses, forming NERVOUS SYSTEM networks through synapses. Supporting cells (neuroglial cells) are nonconducting and The human nervous system has more than 10 billion assist neurons. neurons, grouped into three categories: CNS has oligodendrocytes, astrocytes, microglia, and ependymal cells; PNS has Schwann cells, satellite cells, and others. Sensory neurons Convey impulses from Schwann cells isolate nerve processes; satellite cells receptors to the CNS. surround nerve cell bodies. Somatic afferent fibers Enteric neuroglial cells support ganglia in the alimentary canal. Visceral afferent fibers Neuroglial cell functions: Pain and other sensations from internal organs, glands, o Support, protection, insulation, repair, fluid regulation, and blood vessels. neurotransmitter clearance, and metabolic exchange. Motor neurons Convey impulses from the Blood vessels in CNS and PNS are separated from nerve CNS or ganglia to effector tissue by basal laminae. cells. Blood-brain barrier restricts substance movement into the CNS. Somatic efferent neurons: Voluntary impulses to skeletal muscles. Visceral efferent neurons: Involuntary impulses to REF: PAWLINA 1  TRANS: NERVE TISSUE smooth muscle, Purkinje fibers, and glands. NEURONS ARE CLASSIFIED ON THE BASIS OF THE NUMBER OF Interneurons Form a network between PROCESSES EXTENDING FROM THE CELL BODY sensory and motor neurons, comprising over 99.9% of all neurons. Multipolar neurons: Impulses travel from dendrite One axon and two to cell body to axon. or more dendrites. Dendrites and cell body are THE FUNCTIONAL COMPONENTS OF A NEURON INCLUDE THE CELL receptors; axon conducts BODY, AXON, DENDRITES, AND SYNAPTIC JUNCTIONS impulses. Synaptic endings contain The cell body (perikaryon) of a neuron contains the neurotransmitters. nucleus and organelles that maintain the cell. Motor neurons and Neurons have a single axon, the longest process, interneurons are mostly transmitting impulses away from the cell body to a multipolar. synapse. Bipolar neurons: Rare, associated with special The synapse contacts another neuron or effector cell (e.g., One axon and one senses (taste, smell, hearing, muscle or glandular cell). dendrite. sight, equilibrium). Neurons typically have many dendrites, shorter processes Found in the retina and transmitting impulses toward the cell body from other vestibulocochlear nerve neurons. ganglia. Some, like amacrine cells, lack axons. Pseudounipolar One branch extends to neurons: One axon the periphery, the other to that divides into the CNS. two branches. Impulses are generated in peripheral branches, which are the receptor portions. Majority are sensory neurons located near the CNS (dorsal root and cranial nerve ganglia) CELL BODY THE CELL BODY OF A NEURON HAS CHARACTERISTICS OF A PROTEIN-PRODUCING CELL The cell body is the dilated region of the neuron containing a large, euchromatic nucleus with a prominent nucleolus and perinuclear cytoplasm. Perinuclear cytoplasm has abundant rough endoplasmic reticulum (rER) and free ribosomes, supporting protein synthesis. Nissl bodies (stacks of rER) stain with basic dyes and thionine dyes, visible under a light microscope. Perinuclear cytoplasm also contains mitochondria, Golgi apparatus, lysosomes, microtubules, neurofilaments, transport vesicles, and inclusions. Nissl bodies, ribosomes, and sometimes the Golgi apparatus extend into dendrites but not the axon. The axon hillock lacks large organelles and distinguishes axons from dendrites. The euchromatic nucleus, nucleolus, Golgi apparatus, and Nissl bodies indicate high anabolic activity in large cells. NEURONS DO NOT DIVIDE; HOWEVER, IN SOME AREAS OF THE BRAIN, NEURAL STEM CELLS ARE PRESENT AND ARE ABLE TO DIFFERENTIATE AND REPLACE DAMAGED NERVE CELLS. REF: PAWLINA 2  TRANS: NERVE TISSUE Neurons do not replicate, but subcellular components regularly turnover, with lifespans measured in hours, days, DENDRITES AND AXONS or weeks. Constant replacement of enzymes, neurotransmitters, and DENDRITES ARE RECEPTOR PROCESSES THAT RECEIVE STIMULI membrane components supports high synthetic activity. FROM OTHER NEURONS OR FROM THE EXTERNAL ENVIRONMENT. Newly synthesized proteins are transported within neurons through axonal transport. Dendrites receive information from other neurons or the Nerve cells generally do not divide, but some regions of external environment and carry it to the cell body. the adult brain (e.g., olfactory bulb, dentate gyrus) contain Dendrites are located near the cell body, have a larger neural stem cells that can regenerate. diameter than axons, are unmyelinated, tapered, and form Neural stem cells express nestin (240 kDa protein) and dendritic trees. can divide, migrate to injury sites, and differentiate into Dendritic trees increase the receptor surface area of a new neurons. neuron. Research shows newly generated cells can mature into Neuron types are characterized by the extent and shape functional neurons in the adult brain, offering potential for of dendritic trees. treating neurodegenerative disorders like Alzheimer’s and The perinuclear cytoplasm of the cell body and cytoplasm Parkinson’s. of dendrites are similar, except for the Golgi apparatus. Organelles like ribosomes and rER are found in dendrites, especially near their base. AXONS ARE EFFECTOR PROCESSES THAT TRANSMIT STIMULI TO OTHER NEURONS OR EFFECTOR CELLS The axon conveys information away from the cell body to another neuron or effector cell (e.g., muscle). Each neuron has one axon, which may be very long; motor neurons (Golgi type I) may travel over a meter, while interneurons (Golgi type II) have short axons. Axons may form recurrent branches near the cell body and collateral branches, with more branching near target cells. The axon originates from the axon hillock, which lacks large cytoplasmic organelles like Nissl bodies and Golgi cisternae. Microtubules, neurofilaments, mitochondria, and vesicles pass through the axon hillock into the axon. The region between the axon hillock and the beginning of the myelin sheath is called the initial segment, where the action potential is generated. The action potential is triggered by impulses arriving at the axon hillock after being received by the dendrites or cell body. REF: PAWLINA 3  TRANS: NERVE TISSUE SOME LARGE AXON TERMINALS ARE CAPABLE OF LOCAL PROTEIN - Parkinson's disease is caused by the loss of SYNTHESIS, WHICH MAY BE INVOLVED IN MEMORY PROCESSES. dopamine-secreting cells in the substantia nigra and basal ganglia, affecting motor control. Most structural and functional proteins are synthesized in - Symptoms: the nerve cell body and distributed to axons and dendrites - Resting tremor, especially in the hand, worsens with stress via axonal transport. and often affects one side more. Recent studies show that local protein synthesis also - Rigidity (muscle stiffness). occurs in large nerve terminals, such as those in the - Bradykinesia (slowness of movement) and akinesia retina. (difficulty initiating movement). Axon terminals contain polyribosomes and the full - Lack of spontaneous movement. translational machinery for protein synthesis. - Loss of postural reflexes, leading to poor balance and These areas, called periaxoplasmic plaques, have abnormal walking. characteristics of active protein synthesis. - Slurred speech, slow thought, and small handwriting. Protein synthesis in periaxoplasmic plaques is modulated - Causes: by neuronal activity and may be involved in neuronal - Idiopathic Parkinson's disease: Unknown cause, possibly memory processes. hereditary (20% have family history). - Secondary parkinsonism: Caused by infections, toxins, SYNAPSES drugs, or trauma. - Microscopic features: - Degeneration of substantia nigra neurons, loss of NEURONS COMMUNICATE WITH OTHER NEURONS AND WITH pigmentation, gliosis (increase in glial cells), and Lewy bodies EFFECTOR CELLS BY SYNAPSES (protein accumulation). - Treatment: Synapses are specialized junctions between neurons or - Symptomatic: L-Dopa (DA precursor), cholinergic blockers, between axons and effector cells, facilitating impulse and amantadine (stimulates DA release). transmission. - Surgery: Stereotactic surgery to destroy certain brain nuclei, Types of synapses: experimental DA-secreting neuron transplants. o Axodendritic: Between axons and dendrites, often with dendritic spines, linked to memory and learning. SYNAPSES ARE CLASSIFIED AS CHEMICAL OR ELECTRICAL o Axosomatic: Between axons and cell bodies. o Axoaxonic: Between axons and axons. Classification depends on the mechanism of conduction of Synapses are not visible in routine H&E preparations but the nerve impulses and the way the action potential is can be seen with silver precipitation methods like the Golgi generated in the target cells. Thus, synapses may also be method. classified as the following. Presynaptic axons make multiple synaptic contacts with the postsynaptic neuron, including boutons en passant Chemical synapses Impulses are transmitted by and bouton terminals. neurotransmitters released The number of synapses on a neuron correlates with the from the presynaptic neuron. number of impulses it processes. Neurotransmitters diffuse across the synaptic cleft to the postsynaptic neuron or target cell. Ribbon synapses: Found in receptor hair cells of the internal ear and photoreceptor cells of the retina. Electrical synapses Found in invertebrates, containing gap junctions that allow ion movement between cells. No neurotransmitters required; electrical current spreads directly between cells. In mammals, gap junctions are found in smooth muscle and cardiac muscle cells. A TYPICAL CHEMICAL SYNAPSE CONTAINS A PRESYNAPTIC ELEMENT, SYNAPTIC CLEFT, AND POSTSYNAPTIC MEMBRANE Components of a typical chemical synapse include the following: Presynaptic The end of the neuron where element neurotransmitters are released. REF: PAWLINA 4  TRANS: NERVE TISSUE Contains synaptic vesicles (30-100 nm) with neurotransmitters. Vesicle fusion to the presynaptic membrane is mediated by SNARE proteins (v-SNARE and t-SNARE). Synaptotagmin 1 replaces the SNARE complex for vesicle release. Active zones are areas on the presynaptic membrane where neurotransmitters are released, rich in proteins like Rab-GTPase and synaptotagmin. Vesicle membrane is retrieved via endocytosis and reprocessed by the smooth endoplasmic reticulum. Small mitochondria are present. Synaptic cleft A 20-30 nm space between the presynaptic neuron and THE NEUROTRANSMITTER BINDS TO EITHER TRANSMITTER-GATED the postsynaptic neuron or CHANNELS OR G-PROTEIN–COUPLED RECEPTORS ON THE target cell. POSTSYNAPTIC MEMBRANE. Postsynaptic Contains receptors that membrane interact with neurotransmitters. Neurotransmitters bind to transmitter-gated channels on Formed from the plasma the postsynaptic membrane. membrane of the postsynaptic Binding induces a conformational change, opening the neuron, with an underlying channel pores. dense layer (postsynaptic Influx of Na⁺ causes depolarization, which may lead to density). nerve impulse generation. The postsynaptic density Some neurotransmitters bind to G-protein–coupled is a protein complex that receptors for longer-lasting responses. translates G-protein activation triggers effector proteins, including ion neurotransmitter–receptor channels and enzymes. interactions into intracellular Different receptor systems generate various postsynaptic signals, and anchors receptors actions for some neurotransmitters. and proteins that modulate receptor activity. POROCYTOSIS DESCRIBES THE SECRETION OF NEUROTRANSMITTER THAT DOES NOT INVOLVE THE FUSION OF SYNAPTIC VESICLES WITH Synaptic Transmission THE PRESYNAPTIC MEMBRANE VOLTAGE-GATED CA2 CHANNELS IN THE PRESYNAPTIC MEMBRANE An alternate model of neurotransmitter release, called REGULATE TRANSMITTER RELEASE porocytosis, has been proposed. In this model, neurotransmitter secretion occurs without Depolarization opens voltage-gated Ca²⁺ channels in the vesicle membrane fusion. synaptic bouton. The synaptic vesicle is anchored near Ca²⁺ channels by Ca²⁺ influx causes synaptic vesicles to fuse with the SNARE and synaptotagmin proteins. presynaptic membrane. Ca²⁺ causes the vesicle and presynaptic membranes to Neurotransmitter is released into the synaptic cleft via form a transient pore. exocytosis. Neurotransmitters are released through this 1-nm pore in SNARE and synaptotagmin proteins mediate vesicle a controlled manner. docking and fusion. Neurotransmitter release can also occur through porocytosis. Presynaptic membrane forms endocytotic vesicles for recycling or reloading. REF: PAWLINA 5  TRANS: NERVE TISSUE Synaptic Transmission Numerous molecules function as neurotransmitters in the nervous system. Neurotransmitters diffuse across the synaptic cleft to the postsynaptic membrane and bind to specific receptors. The action of each neurotransmitter depends on its chemical nature and the receptor type on the postsynaptic cell. NEUROTRANSMITTERS ACT EITHER ON IONOTROPIC RECEPTORS TO OPEN MEMBRANE ION CHANNELS OR ON METABOTROPIC RECEPTORS TO ACTIVATE G-PROTEIN SIGNALING CASCADE Neurotransmitters act on ionotropic and metabotropic receptors: o Ionotropic receptors: Ligand-gated ion channels that generate action potentials upon neurotransmitter binding. o Metabotropic receptors: Interact with G-proteins to modulate neuronal activity via second messengers. Acetylcholine (ACh) Neurotransmitter in neuromuscular junction and autonomic nervous system (ANS). Nicotinic receptors: Ion channels, cause muscle contraction. Muscarinic receptors: Modulate heart rhythm. Affected by drugs like curare (blocks nicotinic receptors) and atropine (blocks muscarinic receptors). Catecholamines Includes norepinephrine (NE), epinephrine (EPI), and dopamine (DA). Synthetized from tyrosine, regulate mood, attention, and movement. Adrenergic neurons release EPI in the ANS and during fight-or-flight response. Serotonin (5-HT) Synthesized from tryptophan. Functions in the CNS and enteric nervous system. THE CHEMICAL NATURE OF THE NEUROTRANSMITTER DETERMINES Important for right-left development THE TYPE OF RESPONSE AT THAT SYNAPSE IN THE GENERATION OF in embryos. NEURONAL IMPULSES. Amino acids as GABA, glutamate (GLU), aspartate neurotransmitters (ASP), and glycine (GLY). Excitatory synapses release neurotransmitters like Nitric oxide (NO) Synthesized and used immediately acetylcholine, glutamate, or serotonin. in synapses. These neurotransmitters open Na⁺ channels, causing Modulates neuronal action depolarization and initiating an action potential. potentials via cGMP Inhibitory synapses release neurotransmitters like GABA Small peptides as Includes substance P, B-endorphin, or glycine. neurotransmitter enkephalins, vasoactive These neurotransmitters open Cl⁻ channels, causing intestinal peptide (VIP), hyperpolarization and making action potential generation cholecystokinin (CCK), and harder. neurotensin. Nerve impulse generation in postsynaptic neurons Act locally (paracrine) or at distant depends on the summation of excitatory and inhibitory targets via bloodstream inputs. (endocrine). Synapses process neuronal input and modify impulses by influencing presynaptic or postsynaptic neurons. REF: PAWLINA 6  TRANS: NERVE TISSUE NEUROTRANSMITTERS RELEASED INTO THE SYNAPTIC CLEFT MAY Develop from neural crest cells and express transcription BE DEGRADED OR RECAPTURED factor Sox-10 Produce myelin sheath in PNS to surround and isolate Neurotransmitter degradation or recapture limits axons, aiding rapid nerve impulse conduction postsynaptic stimulation or inhibition duration Axon hillock and terminal arborizations are not myelinated High-affinity reuptake removes 80% of neurotransmitters Unmyelinated fibers are enveloped by Schwann cell via presynaptic transport proteins cytoplasm Transported neurotransmitters are either destroyed or Assist in PNS debris cleanup and guide PNS axon reloaded into vesicles regrowth Catecholamine reuptake uses Na+-dependent transporters; blocked by drugs like amphetamine and MYELINATION BEGINS WHEN A SCHWANN CELL SURROUNDS THE cocaine to prolong effects AXON AND ITS CELL MEMBRANE BECOMES POLARIZED Excess catecholamines are inactivated by COMT or destroyed by MAO Myelination begins with the axon in a groove on the MAO inhibitors treat depression; COMT inhibitors also Schwann cell surface developed Each Schwann cell encloses a 0.08- to 0.1-mm segment Remaining 20% of neurotransmitters degraded by of the axon postsynaptic enzymes Schwann cell surface becomes polarized into two AChE degrades ACh into acetic acid and choline; AChE membrane domains: inhibitors treat myasthenia gravis, glaucoma, Alzheimer’s o Abaxonal membrane: exposed to external environment/endoneurium AXONAL TRANSPORT SYSTEMS o Adaxonal (periaxonal) membrane: in direct contact with the axon SUBSTANCES NEEDED IN THE AXON AND DENDRITES ARE Mesaxon forms as a third domain, connecting abaxonal SYNTHESIZED IN THE CELL BODY AND REQUIRE TRANSPORT TO and adaxonal membranes and enclosing a narrow extracellular space THOSE SITES Neurons have axonal and dendritic processes; nerve cell body is main site for synthesis THE MYELIN SHEATH DEVELOPS FROM COMPACTED LAYERS OF Axonal transport moves materials bidirectionally between SCHWANN CELL MESAXON WRAPPED CONCENTRICALLY AROUND cell body and axon terminal THE AXON Anterograde transport (kinesin, ATP) moves materials from cell body to periphery Myelin sheath formation begins as the Schwann cell Retrograde transport (dynein) moves materials from axon mesaxon surrounds and spirals around the axon terminal and dendrites to cell body Initial layers have cytoplasm in the first concentric layers; Slow transport (0.2-4 mm/day, anterograde only) moves TEM shows a 12-14 nm gap structural elements and cytoplasmic proteins Cytoplasm is eventually squeezed out as layers compact, Fast transport (20-400 mm/day, anterograde and creating the compact myelin sheath retrograde) moves organelles, small molecules, and Sheath of Schwann (outer collar) contains the Schwann endocytosed materials; requires ATP and microtubule cell's nucleus and organelles, surrounded by abaxonal structure plasma membrane and basal lamina Retrograde pathway used by toxins, viruses; also used to Inner collar of Schwann cell cytoplasm lies beneath the trace neuronal pathways with labeled enzymes developing myelin, enclosed by adaxonal plasma Dendritic transport mirrors axonal transport in function and membrane characteristics Compact myelin sheath formation involves transmembrane myelin-specific proteins (P0, PMP22, MBP) SUPPORTING CELLS OF THE NERVOUS SYSTEM: P0 and MBP bring inner leaflets close, appearing as major THE NEUROGLIA dense lines in TEM; outer leaflets form intraperiod lines with a 2.5 nm extracellular gap containing P0 P0 is essential for myelin structure; mutations in P0 can PERIPHERAL NEUROGLIA lead to demyelinating diseases Peripheral neuroglia include Schwann cells, satellite cells, and other specialized cells Terminal neuroglia (teloglia) associate with motor end plate Enteric neuroglia associate with ganglia in the alimentary canal wall Müller’s cells are found in the retina SCHWANN CELLS AND THE MYELIN SHEATH IN THE PNS, SCHWANN CELLS PRODUCE THE MYELIN SHEATH Schwann cells support myelinated and unmyelinated nerve fibers REF: PAWLINA 7  TRANS: NERVE TISSUE THE THICKNESS OF THE MYELIN SHEATH AT MYELINATION IS DETERMINED BY AXON DIAMETER AND NOT BY THE SCHWANN CELL Myelination involves axon-Schwann cell communication Axon determines the number of myelin layers, not the Schwann cell Myelin sheath thickness regulated by neuregulin (Ngr1), a growth factor Ngr1 is a transmembrane protein on the axon’s cell membrane (axolemma) THE NODE OF RANVIER REPRESENTS THE JUNCTION BETWEEN TWO ADJACENT SCHWANN CELLS. Myelin sheath is segmented by Schwann cells along the axon Junctions between Schwann cells are myelin-free, called nodes of Ranvier Myelin between nodes is called internodal segment Nodes of Ranvier regenerate electrical impulses for high-speed axon propagation Highest density of voltage-gated Na channels at nodes, regulated by Schwann cell perinodal cytoplasm Myelin consists of 80% lipids; Schwann cell cytoplasm is extruded between plasma membrane layers Small amounts of cytoplasm remain in specific locations: o Inner collar of Schwann cell cytoplasm between axon and myelin o Schmidt-Lanterman clefts within myelin layers o Perinodal cytoplasm at node of Ranvier o Outer collar of perinuclear cytoplasm around myelin Cytoplasm in clefts contains lysosomes, mitochondria, microtubules, and dense bodies Number of Schmidt-Lanterman clefts correlates with axon diameter; larger axons have more clefts REF: PAWLINA 8  TRANS: NERVE TISSUE UNMYELINATED AXONS IN THE PERIPHERAL NERVOUS SYSTEM ARE ENVELOPED BY SCHWANN CELLS AND THEIR EXTERNAL LAMINA Unmyelinated PNS nerves are still enveloped by Schwann cell cytoplasm Schwann cells are elongated parallel to axon axis, fitting axons into grooves on their surface Groove lips may be open, exposing axolemma to external lamina, or closed, forming a mesaxon A single axon or a group of axons can be enclosed in one Schwann cell invagination Large Schwann cells may have 20+ grooves, each containing one or more axons In the ANS, bundles of unmyelinated axons often occupy a single groove SATELLITE CELLS Neuronal cell bodies in ganglia are surrounded by satellite cells, which are small cuboidal cells Satellite cells form a complete layer around the cell body, but only their nuclei are visible in H&E preparations In paravertebral and peripheral ganglia, neural cell processes penetrate satellite cells to establish synapses (not in sensory ganglia) Satellite cells maintain a controlled microenvironment around the neuronal body, providing electrical insulation and metabolic exchange Satellite cells function similarly to Schwann cells but do not form myelin Enteric neurons in the ANS are associated with enteric neuroglial cells, which resemble astrocytes Enteric neuroglial cells provide structural, metabolic, and protective support, and may also play roles in neurotransmission and coordinating gut nervous and immune system activities CENTRAL NEUROGLIA Four types of central neuroglia: o Astrocytes: Provide physical and metabolic support for CNS neurons o Oligodendrocytes: Form and maintain myelin in CNS o Microglia: Phagocytic cells with small, dark, elongated nuclei o Ependymal cells: Line brain ventricles and central spinal cord canal Only glial cell nuclei are visible in routine histology; heavy metal staining or immunocytochemistry needed to visualize entire cells Glial cells support neurons physically and functionally, particularly during brain and spinal cord development Radial glial cells provide scaffolding for neuronal migration in the developing neural tube REF: PAWLINA 9  TRANS: NERVE TISSUE ASTROCYTES ARE CLOSELY ASSOCIATED WITH NEURONS TO SUPPORT AND MODULATE THEIR ACTIVITIES. Astrocytes are the largest neuroglial cells, forming a network to support and modulate neuron activities Some astrocytes span the brain's thickness as scaffolds for neuron migration during development Processes extend from blood vessels to neurons, with end feet covering vessel or axolemma surfaces Astrocytes do not form myelin Two types of astrocytes: o Protoplasmic: Found in gray matter with short, branching processes o Fibrous: Found in white matter with fewer, straighter processes Both types contain intermediate filaments with glial fibrillary acidic protein (GFAP); more in fibrous astrocytes GFAP antibodies used to stain astrocytes; fibrous astrocytomas (80% of adult brain tumors) identified by GFAP Functions: o Move metabolites and wastes between neurons o Maintain blood-brain barrier by supporting capillary tight junctions o Cover "bare areas" of myelinated axons at nodes of Ranvier and synapses o Constrain neurotransmitters in synaptic cleft and remove excess via pinocytosis o Protoplasmic astrocytes form the glia limitans barrier around the CNS with subpial feet ASTROCYTES MODULATE NEURONAL ACTIVITIES BY BUFFERING THE K CONCENTRATION IN THE EXTRACELLULAR SPACE OF THE BRAIN Astrocytes regulate K+ concentrations in the brain's extracellular compartment, maintaining the neuronal microenvironment Astrocyte plasma membrane has K+ pumps and channels for transferring K+ ions from high to low concentration areas Intracellular K+ accumulation in astrocytes reduces local extracellular K+ gradients Astrocyte membrane depolarization spreads charge across astrocyte network This K+ concentration maintenance by astrocytes is called potassium spatial buffering REF: PAWLINA 10  TRANS: NERVE TISSUE OLIGODENDROCYTES PRODUCE AND MAINTAIN THE MYELIN SHEATH MICROGLIA POSSESS PHAGOCYTOTIC PROPERTIES IN THE CNS Microglia are phagocytic cells, making up about 5% of Oligodendrocytes produce CNS myelin, forming the myelin adult CNS glial cells sheath through concentric layers of plasma membrane Proliferate and become reactive in response to injury or More complex than Schwann cell myelination in the PNS disease Appear as small cells with few processes, often in rows Part of the mononuclear phagocytic system, originating between axons from GMP cells Each oligodendrocyte has several processes, each Enter CNS from the vascular system wrapping a segment of an axon to form an internodal Play roles in defense against microorganisms, neoplastic segment of myelin cells, and debris clearance A single oligodendrocyte may myelinate one or several Mediate neuroimmune reactions, including those in axons nearby chronic pain Processes spiral around axons, staying close until the Smallest neuroglial cells with elongated nuclei and twisted, myelin sheath is complete spiked processes TEM shows lysosomes, inclusions, vesicles, limited rER, and few microtubules or actin filaments EPENDYMAL CELLS FORM THE EPITHELIAL-LIKE LINING OF THE VENTRICLES OF THE BRAIN AND SPINAL CANAL Ependymal cells line fluid-filled CNS cavities with a single cuboidal-to-columnar cell layer Lack external lamina, unlike typical epithelium Tightly bound by apical junctional complexes Basal surface has infoldings that interdigitate with astrocyte processes Apical surface has cilia and microvilli; microvilli absorb cerebrospinal fluid Tanycytes are a specialized ependymal cell type, most numerous in the third ventricle floor o Lack cilia but have long processes projecting into brain parenchyma THE MYELIN SHEATH IN THE CNS DIFFERS FROM THAT IN THE o Transport substances from cerebrospinal fluid to PNS blood in hypothalamic portal circulation o Sensitive to glucose levels; may respond to energy CNS and PNS myelin differ in protein composition balance and monitor metabolites in cerebrospinal fluid o CNS myelin: proteins like PLP, MOG, and OMgp o PNS myelin: proteins like P0 and PMP22 Choroid plexus includes modified ependymal cells and Myelin-specific protein deficiencies are linked to CNS capillaries, producing cerebrospinal fluid autoimmune demyelinating diseases CNS myelin has fewer Schmidt-Lanterman clefts due to IMPULSE CONDUCTION astrocytic support Oligodendrocytes lack an external lamina, so adjacent AN ACTION POTENTIAL IS AN ELECTROCHEMICAL PROCESS myelin sheaths may touch and share an intraperiod line TRIGGERED BY IMPULSES CARRIED TO THE AXON HILLOCK AFTER Nodes of Ranvier are larger in the CNS, enhancing saltatory conduction efficiency OTHER IMPULSES ARE RECEIVED ON THE DENDRITES OR THE CELL CNS unmyelinated neurons are often bare, lacking BODY ITSELF. embedding in glial processes CNS lacks basal lamina and connective tissue Nerve impulse conduction resembles a flame traveling along a fuse REF: PAWLINA 11  TRANS: NERVE TISSUE Involves generation of an action potential initiated at the Ganglion cell development in the PNS involves the axon hillock's initial segment proliferation and migration of ganglion precursor cells from Initial segment membrane contains numerous the neural crest to future ganglionic sites, where they voltage-gated Na and K channels proliferate further In response to stimulus, Na channels open, allowing Na These cells develop processes that connect with target influx, reversing membrane potential from -70 mV to +30 tissues (e.g., glandular tissue or smooth muscle) and mV (depolarization) sensory territories After depolarization, Na channels close, K channels open, Excess cells that fail to connect with target tissues and K exits, restoring resting potential undergo apoptosis Depolarization in one membrane area stimulates Schwann cells originate from neural crest cells, neighboring unstimulated areas, propagating the impulse associating with axons in embryonic nerves Entire process takes less than 1 millisecond Sox10 is essential for generating all peripheral glia from After a brief refractory period, neuron can repeat action neural crest cells potential generation Nrg-1 from axons maintains Schwann cell precursors, promoting differentiation and division along growing RAPID CONDUCTION OF THE ACTION POTENTIAL IS ATTRIBUTABLE nerves TO THE NODES OF RANVIER Schwann cell fate is determined by the diameter of the associated axon: Myelinated axons conduct impulses faster than o Large-diameter axon association leads to myelinating unmyelinated axons Schwann cells Impulse "jumps" from node to node in myelinated axons, o Small-diameter axon association leads to called saltatory or discontinuous conduction non-myelinating Schwann cells Myelin sheath acts as an insulator and does not conduct electric current Voltage reversal occurs only at nodes of Ranvier, where ORGANIZATION OF THE PERIPHERAL NERVOUS the axolemma is exposed and has high concentrations of SYSTEM Na and K channels Impulse jumps from one node of Ranvier to the next The peripheral nervous system (PNS) consists of peripheral Speed of saltatory conduction depends on myelin nerves with specialized nerve endings and ganglia containing thickness and axon diameter; larger diameters increase nerve cell bodies that reside outside the central nervous speed system. Unmyelinated axons have uniformly distributed Na and K channels, resulting in slower, continuous wave conduction PERIPHERAL NERVES A PERIPHERAL NERVE IS A BUNDLE OF NERVE FIBERS HELD ORIGIN OF NERVE TISSUE CELLS TOGETHER BY CONNECTIVE TISSUE CNS NEURONS AND CENTRAL GLIA, EXCEPT MICROGLIAL CELLS, The PNS consists of nerve fibers that carry sensory and ARE DERIVED FROM NEUROECTODERMAL CELLS OF THE NEURAL motor information between organs and the brain/spinal TUBE cord "Nerve fiber" can refer to the axon with its coverings Neurons, oligodendrocytes, astrocytes, and ependymal (myelin and Schwann cell), just the axon, or any process cells originate from neural tube cells of a nerve cell (axon or dendrite) Mature neurons no longer divide, but a small number of Peripheral nerve cell bodies may be in the CNS or in neural stem cells in the adult brain can divide and migrate peripheral ganglia to injury sites, differentiating into functional nerve cells Ganglia contain neuronal cell bodies and their nerve fibers Oligodendrocyte precursors are migratory, sharing lineage Dorsal root ganglia and cranial nerve ganglia contain with motor neurons, migrating to axonal tracts, sensory neuron cell bodies (somatic and visceral proliferating in response to local signals, and matched to afferents) axons via local regulation Cell bodies in paravertebral, prevertebral, and terminal Astrocytes derive from neural tube cells; immature ganglia are postsynaptic motor neurons (visceral efferents) astrocytes migrate and mature in the cortex during early of the autonomic nervous system development Ependymal cells arise from neuroepithelial cells MOTOR NEURON CELL BODIES OF THE PNS LIE IN THE CNS surrounding the neural tube canal Microglia derive from mesodermal macrophage precursors Motor neuron cell bodies that innervate skeletal muscle from GMP cells in bone marrow; they infiltrate the neural are located in the brain, brain stem, and spinal cord tube early, influenced by growth factors like CSF-1 to Axons leave the CNS and travel in peripheral nerves to proliferate and differentiate into motile cells seen in the skeletal muscles developing brain A single neuron conveys impulses from the CNS to the Microglia, the only glial cells of mesenchymal origin, effector organ contain vimentin intermediate filaments for identification via immunocytochemistry SENSORY NEURON CELL BODIES ARE LOCATED IN GANGLIA OUTSIDE OF, BUT CLOSE TO, THE CNS PNS GANGLION CELLS AND PERIPHERAL GLIA ARE DERIVED FROM THE NEURAL CREST. REF: PAWLINA 12  TRANS: NERVE TISSUE In the sensory system, a single neuron connects the distributed among fibroblasts, endothelial cells, receptor to the spinal cord or brain stem macrophages, and mast cells Sensory ganglia are located in the dorsal roots of spinal nerves and in association with sensory components of cranial nerves V, VII, VIII, IX, and X PERINEURIUM IS THE SPECIALIZED CONNECTIVE TISSUE SURROUND- ING A NERVE FASCICLE THAT CONTRIBUTES TO THE FORMATION OF CONNECTIVE TISSUE COMPONENTS OF A THE BLOOD–NERVE BARRIER PERIPHERAL NERVE The perineurium surrounds the nerve bundle and acts as a The bulk of a peripheral nerve consists of nerve fibers and metabolically active diffusion barrier, contributing to the Schwann cells blood-nerve barrier Nerve fibers and Schwann cells are held together by The perineurium maintains the ionic balance of the nerve connective tissue organized into three components: fibers it encloses o Endoneurium: loose connective tissue surrounding Perineurial cells have receptors, transporters, and each individual nerve fiber enzymes for active transport of substances, similar to the o Perineurium: specialized connective tissue endothelial cells of brain capillaries surrounding each nerve fascicle The perineurium can consist of one or more layers, with o Epineurium: dense irregular connective tissue squamous cells, external (basal) lamina on both surfaces, surrounding a peripheral nerve and filling spaces and contractile properties due to actin filaments between nerve fascicles In larger nerves, the perineurium may have multiple layers (up to six), with collagen fibrils between layers and no fibroblasts Tight junctions between perineurial cells form the blood-nerve barrier, and the arrangement of cells is similar to epithelioid tissue Perineurial cells also produce collagen fibrils and have contractile properties, resembling smooth muscle cells and fibroblasts Immune cells (e.g., lymphocytes, plasma cells) are absent from the endoneurium and perineurium due to the protective barrier provided by the perineurium Only fibroblasts, resident macrophages, and occasional mast cells are found within the nerve compartment EPINEURIUM CONSISTS OF DENSE IRREGULAR CONNECTIVE TISSUE THAT SURROUNDS AND BINDS NERVE FASCICLES INTO A COMMON BUNDLE The epineurium is the outermost tissue of the peripheral nerve, consisting of dense connective tissue that surrounds fascicles formed by the perineurium Adipose tissue is often found associated with the epineurium in larger nerve Blood vessels supplying the nerves travel in the epineurium and penetrate into the nerve through the perineurium The endoneurium is poorly vascularized, and metabolic exchange depends on diffusion from and to the blood ENDONEURIUM CONSTITUTES THE LOOSE CONNECTIVE TISSUE vessels through the perineurial sheath ASSOCIATED WITH INDIVIDUAL NERVE FIBERS AFFERENT (SENSORY) RECEPTORS The endoneurium is not easily visible in routine light microscope preparations but can be demonstrated with A PERIPHERAL NERVE IS A BUNDLE OF NERVE FIBERS HELD special connective tissue stains TOGETHER BY CONNECTIVE TISSUE At the electron microscope level, collagen fibrils in the endoneurium are visible, running both parallel to and Receptors initiate nerve impulses in response to stimuli around the nerve fibers, binding them into a fascicle Exteroceptors respond to external stimuli (e.g., Schwann cells likely secrete most collagen fibrils, temperature, touch, smell, sound, vision) supported by tissue culture studies Enteroceptors respond to internal stimuli (e.g., stretch of The endoneurium contains sparse fibroblasts, with mast alimentary canal, bladder, blood vessels) cells and macrophages also present Proprioceptors respond to internal stimuli related to body Macrophages mediate immunologic surveillance and position, muscle tone, and movement participate in nerve tissue repair, proliferating and Simplest receptor is a nonencapsulated (free) nerve phagocytosing myelin debris following nerve injury ending, found in epithelia, connective tissue, and near hair In cross-sections of peripheral nerves, 90% of the nuclei follicles belong to Schwann cells, with the remaining 10% equally REF: PAWLINA 13  TRANS: NERVE TISSUE MOST SENSORY NERVE ENDINGS ACQUIRE CONNECTIVE TISSUE CAPSULES OR SHEATHS OF VARYING COMPLEXITY SYMPATHETIC AND PARASYMPATHETIC DIVISIONS OF THE AUTONOMIC NERVOUS SYSTEM Encapsulated endings are sensory nerve endings with connective tissue sheaths THE PRESYNAPTIC NEURONS OF THE SYMPATHETIC DIVISION ARE Many are mechanoreceptors in the skin and joint capsules LOCATED IN THE THORACIC AND UPPER LUMBAR PORTIONS OF THE (e.g., Krause’s end bulb, Ruffini’s corpuscles, Meissner’s SPINAL CORD corpuscles, Pacinian corpuscles) Muscle spindles are encapsulated sensory endings in The presynaptic neurons send axons from the thoracic skeletal muscle and upper lumbar spinal cord to the vertebral and Golgi tendon organs are encapsulated tension receptors paravertebral ganglia. The paravertebral ganglia in the at musculotendinous junctions sympathetic trunk contain the cell bodies of the postsynaptic effector neurons of the sympathetic division ORGANIZATION OF THE AUTONOMIC NERVOUS SYSTEM THE PRESYNAPTIC NEURONS OF THE PARASYMPATHETIC DIVISION ARE LOCATED IN THE BRAIN STEM AND SACRAL SPINAL CORD Although the ANS was introduced early in this chapter, it is useful here to describe some of the salient features of its Presynaptic parasympathetic neurons originate in brain organization and distribution. The ANS is classified into three stem (midbrain, pons, medulla) and sacral spinal cord divisions: (S2-S4), sending axons to visceral ganglia Ganglia near abdominal/pelvic organs and cranial nerves sympathetic division III, VII, IX, X contain postsynaptic cell bodies for parasympathetic division parasympathetic division enteric division Sympathetic and parasympathetic divisions often innervate same organs with antagonistic effects (e.g., THE ANS CONTROLS AND REGULATES THE BODY’S INTERNAL sympathetic increases heart rate, parasympathetic ENVIRONMENT decreases it) Sympathetic nervous system (SNS) shares functions with ANS in PNS controls involuntary impulses to smooth adrenal medulla due to developmental similarities muscle, cardiac muscle, and glands Both SNS and adrenal medulla cells come from neural Effectors: smooth muscle, cardiac muscle, glands crest, innervated by presynaptic sympathetic neurons, and Term "visceral" characterizes ANS; neurons called visceral release EPI/NE motor (efferent) neurons Sympathetic neurons deliver agents directly to effectors; Visceral motor neurons often accompanied by visceral adrenal medulla releases through bloodstream sensory (afferent) neurons for pain/reflexes to CNS Adrenal medulla may be an exception to the two-neuron Visceral sensory neurons are pseudounipolar, with cell autonomic rule, functioning as a neurosecretory neuron bodies in sensory ganglia, and have long peripheral/central axons Somatic effector (skeletal muscle) uses one neuron from CNS to effector Visceral effector (smooth/cardiac muscle, glands) uses two-neuron chain from CNS to effector Autonomic ganglion outside CNS connects presynaptic to postsynaptic neurons Each presynaptic neuron synapses with multiple postsynaptic neurons ENTERIC DIVISION OF THE AUTONOMIC NERVOUS SYSTEM REF: PAWLINA 14  TRANS: NERVE TISSUE THE ENTERIC DIVISION OF THE ANS CONSISTS OF THE GANGLIA Head AND THEIR PROCESSES THAT INNERVATE THE ALIMENTARY CANAL Parasympathetic presynaptic outflow to the head exits the brain via cranial nerves (see Fig. 12.25) Enteric division of ANS: neurons/processes within Terminal ganglia, such as those in the tongue, contain alimentary canal walls, controls motility, secretions, blood parasympathetic nerve cell bodies flow, and immune/inflammatory responses Sympathetic presynaptic outflow to the head originates in Functions independently from CNS; known as “brain of the the thoracic spinal cord gut” Postsynaptic neuron cell bodies located in the superior Communication with CNS via sympathetic and cervical ganglion parasympathetic fibers essential for digestion Axons from superior cervical ganglion form periarterial Enteroceptors in the gut send sensory info to CNS; CNS plexus along internal and external carotid arteries coordinates sympathetic (inhibits GI activities) and Internal and external carotid plexuses follow carotid artery parasympathetic (stimulates GI activities) responses branches to reach target locations Interneurons process sensory input and relay to enteric motor neurons, triggering reflexes like the gastrocolic Thorax reflex (stomach distention triggers colon contraction) Parasympathetic presynaptic outflow to thoracic viscera Enteric ganglia and postsynaptic neurons located in occurs via the vagus nerve (X) various gut layers from esophagus to anus Postsynaptic neuron cell bodies located in the thoracic Enteric division operates without presynaptic vagus or organ walls or parenchyma pelvic nerve input; peristalsis continues even if these Sympathetic presynaptic outflow to thoracic organs nerves are severed originates from upper thoracic spinal segments Supported by enteric neuroglial cells, not Schwann or Sympathetic postsynaptic neurons for the heart located in satellite cells cervical ganglia; axons form cardiac nerves Pathologic changes in brain neurons, such as Lewy Postsynaptic neurons for other thoracic organs in thoracic bodies and amyloid plaques, also found in enteric sympathetic trunk ganglia neurons, suggesting potential for early diagnostic rectal Axons form pulmonary and esophageal plexuses, traveling biopsies via small splanchnic nerves Abdomen and Pelvis Parasympathetic presynaptic outflow to abdominal viscera via vagus (X) and pelvic splanchnic nerves Postsynaptic neurons in terminal ganglia, often in organ walls, including Meissner’s and Auerbach’s plexuses in the alimentary canal (part of enteric ANS) Sympathetic presynaptic outflow to abdominopelvic organs from lower thoracic and upper lumbar spinal segments Fibers reach prevertebral ganglia via abdominopelvic splanchnic nerves (greater, lesser, least thoracic, lumbar splanchnic nerves) Postsynaptic neuron cell bodies mainly in prevertebral ganglia; exception in adrenal medulla, where presynaptic fibers terminate Extremities and Body Wall No parasympathetic outflow to body wall and extremities Autonomic innervation in body wall exclusively sympathetic Each spinal nerve contains postsynaptic sympathetic fibers (unmyelinated visceral efferents) from neurons in paravertebral ganglia of sympathetic trunk For sweat glands, sympathetic neurons release ACh instead of NE ORGANIZATION OF THE CENTRAL NERVOUS SYSTEM CNS consists of the brain (in cranial cavity) and spinal cord (in vertebral canal) Protected by skull and vertebrae Surrounded by three connective tissue membranes A SUMMARIZED VIEW OF AUTONOMIC (meninges DISTRIBUTION Brain and spinal cord float in cerebrospinal fluid between two inner meningeal layers REF: PAWLINA 15  TRANS: NERVE TISSUE Brain subdivided into cerebrum, cerebellum, and brain stem (connecting with spinal cord) IN THE BRAIN, THE GRAY MATTER FORMS AN OUTER COVERING OR CORTEX; THE WHITE MATTER FORMS AN INNER CORE OR MEDULLA Cerebral cortex is the outermost brain layer, containing nerve cell bodies, axons, dendrites, and central glial cells; site of synapses Cortex appears gray, hence called gray matter Gray matter also found in deep portions of cerebrum and cerebellum (nuclei) White matter contains axons, glial cells, and blood vessels; axons appear white Axons form functionally related bundles called tracts, but no sharp boundaries between adjacent tracts Tracts can be demonstrated through special procedures, like staining or labeling damaged fibers CELLS OF GRAY MATTER EACH FUNCTIONAL REGION OF THE GRAY MATTER HAS A CHARACTERISTIC VARIETY OF CELL BODIES ASSOCIATED WITH A MESHWORK OF AXONAL, DENDRITIC, AND GLIAL PROCESSES Neuropil is the meshwork of axonal, dendritic, and glial processes associated with gray matter Neuropil organization is not visible in H&E-stained sections; other methods are needed for cytoarchitecture analysis Examples of neuron arrangements in cerebral cortex and cerebellar cortex can help appreciate H&E sections Brain stem lacks clear separation of gray and white matter Cranial nerve nuclei in brain stem appear as islands surrounded by white matter tracts Nuclei contain motor neurons' cell bodies and are similar to spinal cord's anterior horns In the reticular formation, the distinction between white and gray matter is less clear ORGANIZATION OF THE SPINAL CORD Spinal cord is a flattened cylindrical structure, continuous with the brain stem, divided into 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal) Each segment is connected to a pair of spinal nerves via dorsal (posterior) and ventral (anterior) roots In cross-section, the spinal cord shows gray matter (butterfly-shaped, surrounding the central canal) and white matter (peripheral) White matter consists of myelinated and unmyelinated axons for communication with other parts of the spinal cord and brain Gray matter contains neuronal cell bodies, dendrites, axons, and central neuroglia Nuclei are functionally related groups of nerve cell bodies in gray matter, similar to ganglia in the PNS Synapses occur only in the gray matter REF: PAWLINA 16  TRANS: NERVE TISSUE THE CELL BODIES OF MOTOR NEURONS THAT INNERVATE STRIATED MUSCLE ARE LOCATED IN THE VENTRAL (ANTERIOR) HORN OF THE GRAY MATTER Ventral motor neurons (anterior horn cells) are large basophilic cells in histologic preparations These efferent neurons conduct impulses away from the CNS to muscles Axons of motor neurons leave the spinal cord, pass through the ventral root, and become part of the spinal nerve Axons are myelinated except at their origin and termination Axons branch near the muscle to form neuromuscular junctions THE CELL BODIES OF SENSORY NEURONS ARE LOCATED IN GANGLIA THAT LIE ON THE DORSAL ROOT OF THE SPINAL NERVE Sensory neurons in the dorsal root ganglia are pseudounipolar They have a single process that divides into a peripheral segment (carries information to the cell body) and a central segment (carries information to the spinal cord) These afferent neurons conduct impulses to the CNS Impulses are generated in the terminal receptor arborization of the peripheral segment CONNECTIVE TISSUE OF THE NERVOUS SYSTEM Three connective tissue membranes (meninges) cover the brain and spinal cord: o Dura mater: outermost layer o Arachnoid: beneath the dura o Pia mater: delicate layer directly on the brain and spinal cord surface Arachnoid and pia mater develop from a single THE DURA MATER IS A RELATIVELY THICK SHEET OF DENSE mesenchymal layer, referred to as pia-arachnoid CONNECTIVE TISSUE In adults, pia mater is the visceral portion, and arachnoid is the parietal portion of the same layer Dura mater in the cranial cavity is continuous with the Arachnoid trabeculae connect pia mater and arachnoid. periosteum of the skull Within the dura mater are venous (dural) sinuses, lined by endothelium, which carry blood from the brain to the internal jugular veins Sheet-like extensions of the inner dura mater form partitions between brain parts, supporting them and carrying the arachnoid to deeper brain regions In the spinal canal, the dura mater forms a separate tube around the spinal cord, with the vertebrae having their own periosteum. THE ARACHNOID IS A DELICATE SHEET OF CONNECTIVE TISSUE ADJACENT TO THE INNER SURFACE OF THE DURA Arachnoid is adjacent to the inner surface of the dura mater Arachnoid trabeculae extend from the arachnoid to the pia mater on the brain and spinal cord Trabeculae are composed of loose connective tissue fibers with fibroblasts The subarachnoid space, bridged by the trabeculae, contains cerebrospinal fluid. THE PIA MATTER LIES DIRECTLY ON THE SURFACE OF THE BRAIN AND SPINAL CORD. REF: PAWLINA 17  TRANS: NERVE TISSUE Pia mater is a delicate connective tissue layer on the Astrocytes play a key role in maintaining tight junctions surface of the brain and spinal cord and barrier integrity. It is continuous with the perivascular connective tissue In brain diseases, the blood-brain barrier loses sheath of blood vessels effectiveness, with visible changes in tight junctions and Both the inner surface of the pia mater and the arachnoid astrocyte morphology. trabeculae are covered by a thin squamous epithelial layer Arachnoid and pia mater fuse around the openings for cranial and spinal nerves as they exit the dura mater. THE BLOOD–BRAIN BARRIER RESTRICTS PASSAGE OF CERTAIN IONS AND SUBSTANCES FROM THE BLOODSTREAM TO TISSUES OF THE CNS Pinocytosis across brain endothelial cells is severely restricted, with few small vesicles observed. Molecules greater than 500 Da generally cannot cross the blood-brain barrier. O2, CO2, and lipid-soluble molecules (e.g., ethanol, BLOOD-BRAIN BARRIER steroid hormones) easily pass through the endothelial cells and blood-brain barrier. THE BLOOD–BRAIN BARRIER PROTECTS THE CNS FROM Astrocytes buffer extracellular K+ concentration in the FLUCTUATING LEVELS OF ELECTROLYTES, HORMONES, AND TISSUE brain, assisted by endothelial cells in limiting K+ movement into the extracellular fluid. METABOLITES CIRCULATING IN THE BLOOD VESSELS Specific receptor-mediated endocytosis allows substances like glucose, amino acids, nucleosides, and vitamins to The blood-brain barrier was first observed over 100 years cross via active transport using transmembrane carrier ago when vital dyes injected into the bloodstream did not proteins. penetrate the brain. The permeability of the blood-brain barrier depends on the It develops early in the em