blood brain barrier + cerebrospinal fluid

• Neurones and astrocytes are separated by narrow clefts about 20 nm wide.
• Astrocytic processes are blue.
• If we take the dimensions of this lecture theatre to represent a neurone 20 μ m in diameter, the ECS is about 50 cm wide.
• ECF accounts for 15 - 20% of brain volume.
• The brain ECF occupies the ECS.
• Factors regulating passage across the Blood Brain Barrier include higher uptake transport, plasma binding, and degree of ionisation.
• The “tight junctions” are replaced by normal fenestrated endothelia in the brain areas lacking a BBB.
• Drugs ionised at physiological pH (7.4) have less access across the Blood Brain Barrier.
• The brain areas lacking a BBB are called the circumventricular organs.
• The Blood Brain Barrier is regulated by factors such as lipid solubility, degree of ionisation, and degree of plasma protein binding.
• Drug pKa value is the pH at which 50% of drug molecules are ionised.
• Capillary Endothelium cells of the brain capillaries have TIGHT JUNCTIONS not FENESTRATIONS as other capillaries, limiting access to molecules with MW greater than 2000.
• The BBB protects the ECF from fluctuations in blood composition and limits entry of compounds into the ECF.
• Glial cells (astrocytes) condition the ECF.
• The ECF cannot be described meaningfully in isolation because of its interactions with the CSF, neurones and glial cells.
• Facilitated transport includes L-glucose and some amino acids.
• Organum vasculosum of the lamina terminalis (OVLT) - important for actions of cytokines in the periphery (fever).
• Area postrema: chemoreceptor zone - vomiting.
• Differences between plasma and CSF include tight junctions, active transport, and the role of choroid plexus & arachnoid villi.
• Some drugs enter brain others are excluded due to lipid solubility or degree of ionisation.
• Pick up releasing hormones for carriage via pituitary portal system to the anterior pituary.
• Concentrations of solutes in the ECF fluctuate with neuronal activity, and changes in the ECF composition affect neuronal behaviour.
• The brain controls the composition of the ECF by synthesizing CSF, regulating the BBB, and conditioning the ECF through glial cells (astrocytes).
• CSF fills ventricles (30 mls) and forms a thin layer around the brain and spinal cord in the subarachnoid space (120 mls).
• The volume of CSF is 150 mls with 500 ml produced each day.
• CSF turns over three times a day.
• CSF secretion pushes existing CSF into the subarachnoid space.
• CSF acts as a cushion or shock-absorber.
• The specific gravity of the brain (1.040) and the SG of CSF (1.007) render the brain buoyant (1400g weighs 50g).
• CSF reduces acceleration-deceleration injuries.
• CSF provides an appropriate local environment for neurones and glia.
• CSF acts as a medium of exchange between brain ECF and systemic blood.
• CSF removes waste products from metabolism, drugs, and neurotransmitter metabolites.
• CSF acts as an interface between the brain and the Peripheral Endocrine Functions, releasing hormones from the hypothalamus.
• CSF circulates in the ventricle system via three foramina projecting into the subarachnoid space (SAS) that permit CSF circulation around the brainstem, cerebellum, and cerebral cortex.
• The ventricle system structures are embryologically derived from the centre of the neural tube during development.
• Glucose (mg/dl) is 100 in plasma and 64 in CSF.
• Cholesterol (mg/dl) is 175 in plasma and 0.2 in CSF.
• The blood-CSF barrier (choroid plexus) is a site of CSF entry.
• The basement membrane, endothelium, glial cells, neurons, subependymal glial cells, ependyma, choroid plexus, and connective tissue are sites of CSF entry.