Neurophysiology Part 4 - CSF and BBB Summer 2024 PDF

Andre Azevedo, DVM, MSc Locum Professor of Veterinary Physiology [email protected]  At the end of the lecture, students should be able to: List the 3 meninges and their characteristics Describe where the CSF is formed and absorbed List the functions of the CSF...

Andre Azevedo, DVM, MSc Locum Professor of Veterinary Physiology [email protected]  At the end of the lecture, students should be able to: List the 3 meninges and their characteristics Describe where the CSF is formed and absorbed List the functions of the CSF Describe the cause of the blood-brain barrier low permeability and how some important nutrients are transported across it FYI  https://www.youtube.com/watch?v=asQo6cmOjd0  The brain and spinal cord are surrounded by 3 layers of connective tissue called meninges 1. DURA MATER 2. ARACHNOID 3. PIA MATER skull dura mater arachnoid subarachnoid space (filled with CSF) arachnoid trabeculae pia mater brain parenchyma  outer PeriosteallayerofDura Mater Duralsinus Inner Meningeal layer mater ofDura 1. DURA MATER dorsal subarachnoid epidural space dura mater (L. durus = hard / mater = mother) space (filled with CSF) Outermost meningeal layer arachnoid pia mater Fused with the inner surface of the skull Thicker, protects the CNS subarachnoid dorsal sagittal skull dura mater space sinus (filled with CSF) acting vertebrae ventral spinal cord subarachnoid central canal space arachnoid (filled with CSF) (filled with CSF) brain parenchyma longitudinal pia mater fissure  SPINAL CORD 2. ARACHNOID Gr. Arachne = web; eidos = form Spiderweb appearance meninge Extensive network of trabeculae that joins BRAIN the pia mater Thin, loose connective tissue layer Subarachnoid space Between arachnoid and pia mater Traps cerebrospinal fluid CSF circulates and is absorbed here  SPINAL CORD softmother 3. PIA MATER (L. Pia = soft) Innermost meningeal layer Adheres to the surface of the CNS BRAIN skull dura mater arachnoid subarachnoid space (filled with CSF) arachnoid trabeculae pia mater brain parenchyma  CNS accounts for only 2% of the body weight but has a desproporcional high metabolic rate and receives 20% of the total cardiac output The oxygen requirements of the synapses and cell bodies are greater than those for axons Grey matter receives more blood than white matter Association/integration areas have greater requirements than other areas Forebrain is more vascular than other CNS regions FYI FYI  The CNS and meninges are drained by veins and sinuses  The CNS and meninges are drained by veins and sinuses Vein: 3 layers, thin smooth muscle layer, valves Sinus: no smooth muscle, no valves – only endothelium and collagen tissue around  The ventricular system comprises 4 expanded regions forming ventricles, interconnecting foramina and tubes Lateral ventricles – oriented longitudinally in each hemisphere and connected with the 3rd ventricle Third ventricle – surrounding the inter thalamic adhesion and connected with the 4th ventricle Fourth ventricle – connected with the subarachnoid space and central canal of the spinal cord LATERAL VIEW OF THE VENTRICULAR CHAMBERS DORSAL VIEW OF THE VENTRICULAR CHAMBERS  lateral fourth ventricles ventricle Practice CSFFlowfromventricles interventricular foramen brain spinal cord third mesencephalic subarachnoid central ventricle aqueduct space canal lateral fourth ventricles ventricle  The ventricular system is lined by EPENDYMAL CELLS The ependyma is a single-layered, cuboidal to the columnar epithelium that lines: The ventricular system of the brain The central canal of the spinal cord The cilia project into the CSF and beat in a coordinated manner Creates the CSF flow The ependymal cells of the choroid plexus are highly specialized Choroid plexus epithelial cells – they form the CSF  the Most of the CSF is formed at the Choroid Plexus of the ventricles The choroid plexus is a cauliflower-like growth of capillaries covered by a thin layer of modified ependymal cells (the choroid epithelium) CHOROID PLEXUS AT THE FOURTH VENTRICLE  Most of the CSF is formed at the Choroid Plexus of the ventricles The choroid plexus is a cauliflower-like growth of capillaries covered by a thin layer of modified ependymal cells (the choroid epithelium) ventricle lumen (filled with CSF) choroid plexus ependymal cells brain parenchyma  Most of the CSF is formed at the Choroid Plexus of the ventricles Other sites: Ependymal lining of the ventricles 42% 35% 23% from (capillaries  parenchyma  ventricles) from lateral and from fourth subarachnoid ventricle Glial limiting membrane between space third ventricles brain/spinal cord and pia mater (capillaries  parenchyma  subarachnoid space) Leptomeningeal capillaries (capillaries  subarachnoid space) In red: choroid plexi  “SEAM” RECALL TIGHT JUNCTIONS Seal the gap between epithelial cells Seal the intercellular space from the luminal environment Seal is not absolute Impermeable to macromolecules Permeability to ions and other small molecules varies Serve as selective permeability barriers for paracellular transport Most apical location Found in epithelial cells EX: lining the intestinal mucosa, bladder, etc.  The Choroid epithelium forms a selective tight-junction barrier Membrane transporters and selective channels regulate the passage of ions and molecules across the epithelial cell barrier Controls the composition of the CSF that enters the ventricles Created from blood plasma 99% Water, different [ ] of ions, and almost no proteins Micronutrients (Vit B6, folates, Vit C)  A.T ActiveTransport Water in the choroid epithelial cells combines with intracellular CO2 produced by cell metabolism to form H+ and HCO3- At the basal surface, H+ is exchanged for extracellular Na+ from the blood AT primary Na+ is pumped out through the apical surface into the ventricles Influx of Na+ into the ventricles results in excess positive charge To neutralize this, Cl- and HCO3- move into the ventricles basal apical Water also diffuses into the ventricles to maintain osmotic balance  NEURONS AND NEUROGLIA CELLS RECEIVE ESSENTIAL MATERIALS VIA 2 ROUTES: Capillaries in the choroid plexus provide micronutrients Interstitial capillaries provide oxygen and substances consumed in large amounts micromeaning small cellneeds nutrients quantityof molecule notmacrovsmicro amounts macro Huff farge miniftrients macro  s of FX Alfa CSF is a clear colorless fluid that has several functions including: Protect brain and spinal cord against impact upon their surrounding bony walls; Effective waste control system that can remove potentially harmful cellular metabolites; Act as a brain distribution system for some peptide hormones and growth factors; Maintain a consistent extracellular microenvironment for the neurons and glia  LATERAL VENTRICLES INTERVENTRICULAR FORAMEN THIRD VENTRICLE MESENCEPHALIC AQUEDUCT FORTH VENTRICLE frontal temporal SUBARACHNOID CENTRAL CANAL SPACE meninarow Four ARACHNOID VILLUS DORSAL SAGITTAL SINUS mesencephalic VEINS  CSF rate of formation, flow, and absorption are sufficiently high to cause its replacement several times daily (3x-5x) Formation is fairly constant and independent of changes in pressure 1 mL/hr in cats; 3 mL/hr in dogs; 20 mL/hr in humans Most of the CSF is absorbed from the subarachnoid space into the venous sinuses through ARACHNOID VILLI Small finger-like projections of the arachnoid membrane that poke through the dura mater in the lumen of venous sinuses arachnoid villi dorsal sagittal sinus dura mater arachnoid subarachnoid space (filled with CSF) choroid plexy  Absorption of CSF appears to be pressure dependent and unidirectional CSF can flow from subarachnoid space to venous outflow system Constituents of the fluid, including waste products and other foreign matter (ex: red blood cells), move into the sinus in water Venus blood cannot normally move back into the subarachnoid space  cell count, morphology, and chemical constituents of CSF can be sampled Commom diagnostic procedure for CNS diseases (Spinal Tap) cisterna magna lumbar puncture Myelography injection of radiopaque dyes into the CSF of the subarachnoid space Often used in conjunction with a CT scan to access the integrity of the spinal canal  Barriers exist between the blood and the CSF and brain fluid Concentrations of several important constituents of CSF are not the same as in extracellular fluid Many larger molecules hardly pass at all from the blood into the cerebrospinal fluid or the interstitial fluids of the brain These substances pass readily into the interstitial fluids of the body  They are located both at the choroid plexus and at the tissue capillary membranes in all areas of the brain Except for some areas like the hypothalamus, and the pineal gland They have sensory receptors that respond to specific changes in the body fluids, such as osmolality and glucose concentration  The cause of the low permeability of the barrier is how the cells are joined to one another Membranes of the adjacent endothelial cells are tightly fused rather than having large slit pores between them  Astrocytes form a perivascular end feet around the entire outer surface of the capillary endothelium Interaction between astrocytes and endothelial cells is important for the maintenance of the BBB  he The BBB has specific carrier molecules that facilitate the transport BBB is highly permeable to water, CO2, O2 and most lipid-soluble substances such as alcohol and anesthetics Silghtly permeable to electrolytes such as sodium, chloride, and potassium Almost totally impermeable to Plasma proteins Non-lipid-soluble large organic molecules  The brain needs certain water-soluble nutrients, but they are restricted from passing through the BBB GLUCOSE Uses GLUT 1 – facilitated diffusion LARGE NEUTRAL AMINOACIDS Ex: Phenylalanine, leucine, tyrosine, isoleucine, valine, tryptophan, methionine, histidine Some are precursors for neurotransmitters (ex: Tryptophan)– use facilitated diffusion SMALL NEUTRAL AMINOACIDS Glycine, alanine, serine, cysteine, proline, gamma aminobutyric acid (GABA) Are synthesized in the CNS  exo f basically  https://www.youtube.com/watch?v=_e60_4ZV0zs  FYI is Lif I iceptionissues pp tothe left 9 a'Ya n'of height FYI  HYDROCEPHALLUS is an abnormal dilation of the ventricular system from an increased volume of CSF Can be congenital or acquired  nochoroidplexusin frontalhorn occipitalhorn vatehntric.v Hn Temporal 4th