BBB

BBB + disease

BBB in pathology - TBI, ishchaemic stroke, inflamm diseases e.g. meningities, toxic derangement can all disrupt BBB Can be utilised clinically e.g. normally blood brain barrier impermeable to penicillin - meningitis, penicillin can be used as treatment as BBB disrupted and becomes more permeable and allows Rx of infection

What is its structure

Consists of: - Capillary endothelium - linked by tight junctions (protein based structures - span intercellular cleft) - Astocytes with endfoot - structure separates endothelium from neuronal cells - Pericytes + extracellular matrix, provide structure, pericytes also have phagocytic function Movement through blood brain barrier - 50-100x 'tighter' than peripheral vessels

What moves through blood brain barrier

DIFFUSION Paracellular flux solutes v limited due to tight junctions Movement via transcellular mechanisms - more lipid soluble higher diffusion - low mW more diffusion Small inorganic ions e.g. CO2, O2, H2O therefore move freely CO2 diffusion means central chemoreceptors can respond to changes in CSF pH Highly polar molecules e.g. glucose, aas, amines, - membrane permeability low, therefore require facilitated diffusion via carrier proteins, e.g. glucose via GLUT-1 Large proteins cannot pass through ENDOCYTOSIS - allows uptake macormolcules into CNS e.g. insulin

Discuss physiological significance of the bloood brain barrier

Definition Function - protects, allows Structure Movement across BBB Drugs

Drugs + BBB

Drugs Main determinants as to whether will pass BBB - MW (>600 daltons will not pass through) - Lipophillic drugs (e.g thiopentone pass through) Give morphine derivative diamorphine 100x CNS permeability of morphine

What are its functions

Selective diffusion barrier at the level of cerebral microvasculature - Protects against toxins - Protects against infections (pericytes) - Allows neuronal homeostasis - Separates central neurotransmitters from periphery + vice versa (e.g. noradenaline, water soluble cannot cross) Incomplete / deficient : Certain strategic positions the BBB is deficient : Unprotected regions included area postrema, median eminence, unprotected areas collectively referred to as circumventricular organs : Area postrema is where CTZ trigger zone situated - By sampling plasma, CNS responds by stimulating vomiting centre, a primitive protective mechanism : Permit diffusion of blood borne molecules allowing regulation of endocrine and ANS functions

What is the blood brain barrier

highly regulated interface that separates peripheral circulation + CNS