Structural & Functional Biology - CSF and BBB PDF

Structural & Functional Biology: Cerebrospinal fluid and blood-brain barrier SARAH HOOPER, DVM, PHD E-MAIL: [email protected] Cerebrospinal fluid and blood-brain barrier Learning objectives: • • • • • • • • • Name the three meninges Describe the structure and function of the different meni...

Structural & Functional Biology: Cerebrospinal fluid and blood-brain barrier SARAH HOOPER, DVM, PHD E-MAIL: [email protected] Cerebrospinal fluid and blood-brain barrier Learning objectives: • • • • • • • • • Name the three meninges Describe the structure and function of the different meninges List the functions of the cerebrospinal fluid Where cerebrospinal fluid is formed Explain the flow of CSF through the CNS Explain CSF absorption into the venous system What is hydrocephalus List the components of the blood brain barrier State the importance of a functioning blood brain barrier Cerebrospinal fluid and blood-brain barrier The brain and the spinal cord are enveloped by three sheets of connective tissues, the meninges • Dura mater (thick layer of fibroblasts; it fuses with the bone inner surface of skull bones) • Arachnoid mater (spiderweb-like; thin layer of fibroblasts that trap CSF between it and pia mater) • Pia mater (single layer of fibroblasts) From: Sjaastad, Sand, Hove „Physiology of Domestic Animals“ Cerebrospinal fluid and blood-brain barrier cerebrospinal fluid (CSF) is a clear fluid present in the ventricles of the brain, in the central canal of the spinal cord, and in the subarachnoid space (brain and spinal cord) The Cerebrospinal fluid and blood-brain barrier CSF functions: • To cushion the brain (buffering blows to the head) • Maintaining a consistent extracellular microenvironment for the neurons and glia cells • Waste control system for the removal of potentially harmful cellular metabolites • Distribution medium for peptide hormones and growth factors that are secreted into the CSF Cerebrospinal fluid and blood-brain barrier CSF is produced specialized ependymal cells in choroid plexus located in each of the four ventricles (in the floor or roof) at a relatively constant rate The lateral ventricles are respectively located in the two cerebral hemispheres, the third ventricle is found at the midline of the diencephalon, and the fourth ventricle is located between the cerebellum and the dorsal surface of the hindbrain (pons and medulla) Cerebrospinal fluid and blood-brain barrier The plexuses consist of tufts of capillaries covered by a layer of ependymal cells that form a selective, tight-junction barrier to the secretions of the leaky capillaries and to other surrounding fluids (e.g., CSF, extracellular fluid) Relevant processes:  active transport of sodium ions (Na+) and chloride (Cl-) into the ventricles  water follows the NaCl passively into the ventricle  Metabolization of some potentially harmful waste products Cerebrospinal fluid and blood-brain barrier CSF flows down a pressure gradient from its site of formation at the choroid plexuses through the ventricular system and subarachnoid space into the venous system Lateral ventricles  into the third ventricle through the interventricular foramina (foramina of Monro)  through the cerebral aqueduct (aqueduct of Sylvius) of the midbrain  into the fourth ventricle  into the subarachnoid space through foramina of Luschka Cerebrospinal fluid and blood-brain barrier CSF sampling CSF can be sampled by placing a stilettoed spinal needle into the subarachnoid space In humans  in the lumbar spinal column In most veterinary species  between the skull and the first cervical vertebra (atlas) in anesthetized animals Normal CSF is clear and translucent. Turbidity indicates increased cellularity, and a pink tint suggests the presence of blood From: Sjaastad, Sand, Hove „Physiology of Domestic Animals“ Cerebrospinal fluid and blood-brain barrier CSF absorption into the venous system takes place in dura-lined venous sinuses within the skull  Most of the fluid is absorbed from the subarachnoid space into the dural sinuses through arachnoid villi (small, fingerlike projections of the arachnoid membrane that poke through the walls of the sinus)  Absorption unidirectional appears to be pressure dependent and is CSF is produced at a rate of about 1 mL/hr in cats, about 3 mL/hr in dogs and about 20 mL/hr in humans   The entire volume of CSF is replaced several times a day Cerebrospinal fluid and blood-brain barrier Hydrocephalus: Increased CSF volume in the skull, often associated with an increased ventricular volume and increased intracranial pressure Non-communicating hydrocephalus: Normally caused by an obstruction to CSF flow (narrow cerebral aqueduct or blocked exits from the fourth ventricle)  This causes the ventricular regions inside the brain to expand at the expense of the surrounding brain tissue, and intracranial pressure rises Communicating hydrocephalus: Impairment of absorption (can be secondary to meningitis or hemorrhage)  This can increase CSF volume in the subarachnoid space, which increases pressure on the outside surface of the brain and increases intracranial pressure. Cerebrospinal fluid and blood-brain barrier The blood-brain barrier consists of specialized capillary endothelial cells that are lined by the basal lamina, astrocytic endfeet, pericytes and microglial cells.  In brain capillaries, passage through intercellular clefts is blocked by tight junctions, and exchange of blood solutes is highly selective. From: Ross & Pawlina „Histology: A Text and Atlas“ Cerebrospinal fluid and blood-brain barrier The blood brain barrier--histological characteristics: • Few or no fenestrations • Pinocytosis very uncommon to observe at the BBB • Tight junctions • Luminal and abluminal side of the endothelium (polarized) • Specific carrier systems for the uptake of solutes • Endothelium is surrounded by pericytes and astrocytes Cerebrospinal fluid and blood-brain barrier The blood brain barrier--functional characteristics: • Molecules that are small, uncharged, lipid soluble, and unbound to plasma proteins (e.g., O2, CO2, ethanol, nicotine) can easily pass across the capillary endothelium of the BBB • Molecules that do not fit this profile (e.g., glucose, some amino acids) are able to pass through the BBB by specific, carrier-mediated transport mechanisms • Many antibiotics, anti parasitic drugs, as well as various potentially harmful substances will be “repelled” by the BBB (carrier-mediated process!) and will never reach the nervous tissue Cerebrospinal fluid and blood-brain barrier Transport systems at the BBB (the most representatives): Transport systems for glucose (GLUT) Lactate and ketone bodies (MCT, monocarboxylic acid transporter) Amino acids transporters OATPs/Oatps (Organic Anion Transporting Polypeptide) OCTs/Octs (Organic Cation Transporters) OATs/Oats (Organic Anion Transporters) Pgp: MDRs (Multidrug Resistance Protein) MRPs (Multidrug Resistance Associated Protein) Cerebrospinal fluid and blood-brain barrier Learning objectives: • • • • • • • • • Name the three meninges Describe the structure and function of the different meninges List the functions of the cerebrospinal fluid Where cerebrospinal fluid is formed Explain the flow of CSF through the CNS Explain CSF absorption into the venous system What is hydrocephalus List the components of the blood brain barrier State the importance of a functioning blood brain barrier https://jeopardylabs.com/play/cerebrospinal-fluid-and-bbb