14 Blood-Brain Barrier

14 Blood-Brain Barrier - PSL302Y Lecture 13 by Prof MacKay...

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Unformatted text preview: PSL302Y: Lecture 13, by Prof. MacKay! Blood-Brain Barrier Fri., Oct.15, 2010 Octobe Blood-Brain Barrier Really 3 distinct `barriers': 1) Blood-brain (interstitial fluid) 2) Blood cerebrospinal fluid (ventricles) 3) CSF-interstitial fluid: this is not a real `barrier'; molecules freely diffuse btwn the two compartments Blood (capillaries): ! [Na+] = 140mEq/L ! [K+] = 4.5mEq/L ! [protein] = 7g/dL Interstitial<=>CSF (ventricles): ! [Na+] = 140mEq/L ! [K+] = 2.8mEq/L ! [protein] = 35mg/dL ! -> [K+] and [protein] greatly reduced b/c affect membrane potential and signaling Blood-Brain Barrier Diagram: ! Lateral ventricles (I & II) filled with October 15, 2010 CSF Blood-Brain ! ! IIIrd ventricle: connect to brainstem Barrier ! ! Aqueduct of Sylvius connects IIIrd & IVth; Ivth ventricle: atop brainstem ! ! Central canal connects IVth to spinal cord Brain Encasings (from top to bottom) Brain Encasings -Skull: and vertebrae (bone ) -Dura mater: thick layer of membrane Skull around CNS -Arachnoid membrane: thin layer of dura mater membrane under dura mater arachnoid (CSF) -Subarachnoid space: filled w/ CSF to subarachnoid space; filled with CSF to (CSF) make a suspension cushion = brain floats make a suspension cushion brain -Pia mater: membrane tethered to floats arachnoid by arachnoid `trabeculae' atop pia mater; tethered to arachnoid by of brain tissue arachnoid `trabeculae' -Lgest vessels lie on top of pia mater; smaller vessels penetrate into brain tissue Blood-brain barrier - Epithelial cells around capillaries (endothelial cell walls) = require transport of glucose, etc. across blood-brain barrier (unlike in body) - Astrocytes take up nutrients from capillaries and deliver them to neurons (=bridge) -> produce ATP from nutrients via glycolysis -> form in lines along blood vessels in brain - Most energy consumed (most anabolic activity) at neuron 1 of 6 October 15, 2010 3 Blood-Brain Barrier PSL302Y: Lecture 13, by Prof. MacKay! Fri., Oct.15, 2010 October 15, Local Blood Flow - Opposite to nutrient flow in astrocytes, a metabolic signal moves outwd to blood vessels to signal neuronal activity lvl - Fxn: astrocytes adjust blood flow to diff parts of brain where signaling activity high 1) Glutamate in active neuron synapses triggers Ca2+ release w/i astrocytes 2) Ca2+ wave travels thru astrocytes twd blood vessels = triggers prostaglandin (PGE2) release at end-foot 3) PGE2 -> vasodilation (muscles relaxed in blood vessel) = blood flow to active neural tissue Glial Cell Fxns vasodilation increased blood flow Calcium wave Brain Barrier - Myelination of axons = signal conduction October 15, 2010 - Structural support for neurons - Provide guidance for devlping neurons - `Mop' up transmitters, extracellular K+ (required b/c potential relies on K+ gradient!) - Provide energy substrates (lactate, glutamine) for mitochondria in neurons Glial Cell Functions - Regulate local blood flow myelination of axons structural support for neurons provide guidance for developing neurons `mop' up transmitters, extracellular K+ provide energy substrates (lactate, id b t t (l t t glutamine) for mitochondria in neurons regulate local blood flow immune function Glial Cells Diagram: Types of Glial Cells - Oligodendocytes: like Schwann cells; Microglia: immune cell of the brain 2 of 6 arrier PSL302Y: Lecture 13, by Prof. MacKay! October 15, 2010 Fri., Oct.15, 2010 Ventricles -Continuation of central canal in spinal cord -Filled w/ cerebrospinal fluid (CSF) -Bathing medium of brain (nutrients); highly regulated ionic content (buffer zone), few macromolecules -CSF continuously produced from plasma by choroid plexus lining ventricles: filters plasma, regulates ionic concentrations -CSF exits choroid plexus at IVth Blood-Brain Barrierventricle -> subarachnoid space -CSF drains into venous system (prevent buildup of pressure) - Note: plasma is blood minus rbcs October 15, 201 Choroid Plexus Produces most of CSF (but not all) endothelial wall of capillaries is fenestrated; surrounding epithelial cells connected by tight junctions Cerebrospinal Fluid - Continuously produced by choroid plexus in ventricles filters plasma: water moves down pressure gradient; secretion of Na+, Cl-, glucose, etc. di t ti fN l t - Same osmolarity and [Na+] as blood serum absorption of amino acids, inorganic anions, - BUT greatly reduced [K+], [Ca2+], and [Mg2+]: these can influence brain potentials organic acids, etc. - Total CSF volume = 215mL - Cranial CSF = 140mL (ventricles = 25mL, subarachnoid space = 115mL) - Spinal CSF = 75mL Cerebrospinal Fluid - Produces most of CSF plexus in ventricles Produced by choroid (but not all; some produced w/i brain) Same osmolarity capillaries+is as blood serum - Endothelial wall of and [Na ] fenestrated (not like the blood-brain barrier) Greatly reduced [K+], [Ca2+] and [Mg2+]jxns - Surrounding epithelial cells connected by tight (= volume barrier ml totalblood-brainis 215 = ependymal cells) - Filters plasma: water moves pressure gradient; cranial CSF Na+, Cl-,ml (25 ml i ventricles, i l i l l in ti l secretion of is 140 glucose, etc. - Absorption of amino acids, inorganic 115 ml in subarachnoid space) anions, organic acids, etc. spinal CSF is 75 ml Choroid Plexus 3 of 6 7 PSL302Y: Lecture 13, by Prof. MacKay! Fri., Oct.15, 2010 TINS (2008) 31: p. 280 Summary of Barriers in the Brain - Blood-brain barrier (neurovascular unit): plasma blocked & filtered by epithelial cells - Blood-CSF barrier (at choroid plexus): ependymal cells, NOT the fenestrated endothelial capillary walls! - CSF-brain `barrier': no tight jxns btwn adult ependymal cells -> free diffusion Circulation of CSF CSF produced continously (550 ml/day) flows downward through ventricles and spinal canal flows upward through subarachnoid space 4 of 6 Blood-Brain Barrier Octo PSL302Y: Lecture 13, by Prof. MacKay! Fri., Oct.15, 2010 Circulation of CSF - CSF produced continuously (550mL/ day = replacing entire CSF twice a day!) - Flows downwd thru ventrices&spinal canal, & upwd thru subarachnoid space - Drains via arachnoid villi into cerebral venous sinuses (venous drainage btwn Blood-Brain Barrier brain hemispheres) - Some leakage along cranial nerves (signif amt of drainage occurs here) - Cranial nerves travel away from brain to rest of body, esp at olfactory nerves - Eventually leads back to venous system October 15, 20 Ependyma Cell layer lining the ventricles (CSFinterstitial fluid barrier) Subependymal layer contains multipotent -Superior sagittal sinuses = venous neural stem cells that give rise to progenitor sinus btwn hemispheres cell pool -Below epithelial cap: allow CSF to progenitor cells migrate to rest of space can it t t t fb i escape ll fromi subarachnoid brain; thru differentiate into all types of glial cells or bulge neurons Ependyma -Cell layer lining the ventricles (CSFinterstitial fluid barrier) -Subependymal layer contains multipotent neural stem cells that give rise to progenitor cell pool -Progenitor cells migrate to rest of brain; diffate into all types of glial cells/neurons - Only two places in brain where replacement of neurons go on continuously throughout life (continuous turnover of neurons): olfactory bulb, hippocampus - Under ependymal cells are progenitor cells, which diffate and travel from posterior to anterior of ventricle to where new glial cells/neurons are needed 10 5 of 6 PSL302Y: Lecture 13, by Prof. MacKay! Fri., Oct.15, 2010 Areas Lacking BBB - Fenestrated capillaries are found in `circumventricular organs' (no ependymal cells = no blood-brain barrier): posterior pituitary, median eminence, pineal, area postrema (caudal end of IVth ventricle; important for regulating respiration) - In hypothalamus: need to know what's in the blood stream (i.e. signaling compounds), and to release signaling factors back into blood stream - Areas that interact w/ endocrine system or require sensitivity to metabolites in plasma Summary Blood-interstitial fluid barrier CSF-interstitial fluid `barrier' (free diffusion) diff sion) Blood-CSF barrier 6 of 6 ...
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