Neurophysiology 1A PDF

# NEUROPHYSIOLOGY 1 A Neven Makram Aziz ## Neurophysiology - **Five basic questions:** - How the CNS work? - How do nerve cells in the brain communicate with one another? - How is the communication between neurons modified by experience? - How do different patterns of interconnec...

# NEUROPHYSIOLOGY 1 A Neven Makram Aziz ## Neurophysiology - **Five basic questions:** - How the CNS work? - How do nerve cells in the brain communicate with one another? - How is the communication between neurons modified by experience? - How do different patterns of interconnections give rise to different perceptions and motor acts? - How is that communication altered by disease? ## OBJECTIVES - **A.** Describe the structure and functions of nervous system - **B.** List functions of CSF. - **C.** Recognize the CSF and blood brain barriers. - **D.** Describe mechanism of transport of substances across blood brain barrier. - **E.** Explain mechanisms of brain edema. ## Nervous System - Controls all the activities of the body. - It is quicker than other control system (endocrine system). - **Divided into two parts:** - **Central Nervous System (CNS)** including brain and spinal cord. - **Peripheral Nervous System (PNS)** including somatic nervous system and autonomic nervous system. - **The CNS** is a bilateral and symmetrical structure with two main parts, the spinal cord and the brain: - The brain consists of seven major structures: - **Brain stem** (medulla oblongata, pons, midbrain) - **Cerebellum** - **Diencephalon** (thalamus and hypothalamus) - **Cerebrum** ## The Brain - Is situated in the skull. - It is continued as spinal cord in the vertebral canal through the foramen magnum of the skull bone. - Brain and spinal cord are surrounded by three layers of meninges called: - Outer dura mater - Middle arachnoid mater - Inner pia mater - The space between arachnoid mater and pia mater is known as subarachnoid space (SAS) - This space is filled with a fluid called cerebrospinal fluid (CSF) - The brain and spinal cord are actually suspended in the CSF for: - **Supporting and protection against trauma.** - **Transports nutrients, $O_2$ and large molecules (hormones) to the brain tissue (like any extracellular fluid (ECF).** - **Remove metabolic waste products from the brain tissue.** - **A diagram depicts the brain and spinal cord, including labeled structures like:** - Cerebrum - Midbrain - Pons - Medulla oblongata - Cervical segment - Thoracic segment - Lumbar segment - Sacral segment - Coccygeal segment - **Another diagram depicts the forebrain, midbrain, and hindbrain, highlighting structures such as:** - Thalamus - Cerebral Cortex - Hypothalamus - Corpus callosum - Occipital lobe - Cerebellar cortex - Pituitary gland - Middle brain - Pons - Medulla - Spinal cord ## CSF - (ECF, trans-cellular fluid) - Is secreted by choroid plexus (modified ependymal cells), 60% (and remaining 40% by CNS capillaries) into the brain ventricles to be flow from lateral ventricle to 3rd and 4th ventricles. - **CSF flows from the 4th ventricle into SAS to be removed through arachnoid villi (arachnoid granulations).** - Arachnoid granulations are delicate non-vascular tissue membrane between dura and pia matter. - It allows movement of CSF to the superior sagittal sinus. - From there, it moves to the venous blood while the CSF around the spinal cord drains into the vertebral venous plexuses. - **CSF is secreted from capillary choroid blood and substances must cross 3 layers (Potential barriers):** - Capillary wall (endothelium) - Supporting layer (between capillary wall and epithelium) - Epithelial cell layer (Blood-CSF Barrier) ## Comparison of CSF and plasma - **Major components of CSF are ions:** - CSF is primarily $Na^+$, $Cl^-$ (and $H_2O$). - CSF has about 25% less potassium than plasma. - CSF has about 35% less calcium than plasma. - **CSF composition is more stable than plasma over time:** - Plasma ion concentrations vary (after a meal, during strenuous exercise). - CSF composition fluctuates very little. - Stable ion concentrations are essential for normal neuronal function. - **Diagram depicts the brain ventricles, including:** - Interventricular foramen of Monro - Lateral ventricle - 3rd Ventricle - Cerebral aqueduct - Central canal - 4th ventricle - **Diagram depicts the choroid plexus, including:** - Ependyma (ventricular lining) - Choroid plexus - Brain interstitial spaces - Capillary - Gaps - Tight junction - Synapse - Ventricle - Ependymal cells - Choroid Plexus Epithelium - **Diagram depicts a cross section of the brain, highlighting:** - Superior sagittal sinus - Arachnoid granulation - Subarachnoid space - Ependymal cells - Connective tissue - CSF - Choroid plexus - Lateral ventricle - Opening connecting lateral and third ventricles - Choroid plexus of third ventricle - Cerebral aqueduct - Opening in wall of fourth ventricle - Choroid plexus of fourth ventricle - Opening in roof of fourth ventricle - Subarachnoid space - Central canal of spinal cord - Dura mater ## Blood-CSF Barrier - Created by tight junctions at THE apical membrane surface of modified ependymal cells. - It is characterized by: - **Substances (water, ions) cannot move through tight junctions.** - **Any movement (transport) must occur through choroid plexus epithelial cell membranes.** - **Transport mechanisms in epithelial cell membranes (apical, basolateral and intracellular) create and regulate the production of CSF by secretion.** - **Diagram depicts a close-up of the blood-CSF barrier, including:** - ISF - Apical surfaces - Pinocytosis - Choroid plexus - Capillary endothelial cells - Lipid soluble - Intercellular cleft passage - Pinocytotic vesicle - Fenestra - **Diagram depicts a cross section of the choroid plexus, including:** - Transport of divalent cations ($Ca^{2+}$, $Mg{2+}$), glucose, nucleosides, vitamins from plasma to CSF requires transporters in both basolateral and apical membranes - Basolateral surface - Epithelial cell - Tight junction - Ventricles - Apical surfaces - CSF - Vitamin C - Ribonucleosides and deoxyribonucleosides - Folates - Vitamin B6 - Plasma - $Na^+$ - $H^+$ - $H_2O$ - $Cl^-$ - $CO_2+OH^-$ - $HCO_3^-$ - Enzymes ## The Blood-Brain Barrier (BBB) - **It is the barrier between cerebral capillary blood and interstitial fluid of the brain.** - **Anatomically, the blood-brain barrier consists of capillary endothelial cells and basement membrane, neuroglial membrane, and glial end feet (projections of astrocytes from the brain side of the barrier that don't create BBB but, they secrete trophic factors that cause CNS capillary to have tight junctions Foot).** - **Diagram depicts the blood-brain barrier, including:** - Receptor-mediated transcytosis - Tight junctions - Astrocyte - Carrier-mediated transport - Basal lamina - Pericyte - Transcellular passive diffusion - Interneuron - Restricted paracellular diffusion - Adsorptive-mediated transcytosis - Endothelial cell - Microglia ## Blood-CSF and blood brain barriers characters: - **Tight junction (barrier) in blood-CSF barrier present between modified ependymal cells while in blood brain barrier between capillary endothelial cells. Both have the following functions:** - **Highly permeable to water, carbon dioxide, oxygen, and most lipid-soluble substances such as alcohol and anesthetics.** - **Slightly permeable to electrolytes such as sodium, chloride, and potassium (by transport mechanisms).** - **Almost totally impermeable to plasma proteins and most non-lipid-soluble large organic molecules.** ## Functions of Blood-brain and blood-CSF barriers (protect CNS): - **Provide a constant, controlled environment for the brain cells and to protect the brain from endogenous or exogenous toxins as both barriers make it impossible to achieve effective concentrations of therapeutic drugs, such as a non-lipid-soluble drugs and protein antibodies, in the cerebrospinal fluid or parenchyma of the brain.** - **Prevent escape of local neurotransmitters into the general circulation.** - **N.B. Inflammation, irradiation, and tumors may increase the permeability of the blood-brain barrier and allow substances normally excluded to enter the brain.** ## Cerebral edema - **A disturbance of fluid balance (either interstitial or cellular) and has three types:** - **Vasogenic edema** - Is due to breakdown of BBB as in trauma or meningitis. - Plasma proteins leak into interstitial space, raising ISF osmotic pressure. - Water is drawn from plasma into interstitial space. - Increased interstitial fluid volume. - Leads to rise in intracranial pressure, compression of vasculature, decreased blood flow to brain. - **Interstitial Edema** - Is due to obstructions in passages between ventricles (obstructive hydrocephalus). - Increase CSF pressure inside ventricles force CSF into brain interstitial space. - Fluid accumulation in interstitial space finally causes ventricles to expand. - Leads to rise in intracranial pressure, compression of vasculature, decreased blood flow to brain. - **Cytotoxic (Cellular) Edema** - Is due to cellular ATP depletion. - $Na^+-K^+$ pump failure. - Impaired ability to maintain osmotic balance. - Rises of intracellular osmotic pressure by active particles ($Na^+$). - Draws water into cells. - Leads to increase cell volume can destroy cells.