Blood Brain Barrier

• Fibrous astrocytes, which contain many intermediate filaments, are found primarily in white matter.
• Protoplasmic astrocytes are found in gray matter and have a granular cytoplasm. Both types send processes to blood vessels, where they induce capillaries to form the tight junctions making up the blood–brain barrier.

D. i.e. Area Postrema 

–  Circumventricle organs are out of BBB and include subfornical organ, organum vasculosum (lamina terminalis), neurohypophysis, area postremaQ and medial eminence of hypothalamus.

Blood brain barrier (BBB) is formed by capillary endothelium, basement membrane of endothelium, foot process of astrocytes, neuroglia and ground substance of brain

D i.e. Proteins

Blood-CSF Barrier & Blood-Brain Barriers are highly permeable to water, CO₂ (carbondioxide), 0₂ (oxygen)₂, and most lipid soluble (lipophilic) substances such as free forms of steroid hormones, alcohol and anestheticsQ; slightly permeable to electrolytes like Na⁺ (sodium), K⁺ (potassium) and Cl- (chloride); and almost totally impermeable to plasma proteins, protein bound forms of steroid hormones, protein antibodies and most non lipid soluble large organic molecules (i.e. impermeable to, in general, all proteins and polypeptides)Q. It slows penetration of some smaller molecules like urea.

Blood Brain Barrier (BBB) & Blood Cerebrospinal fluid Barrier (BCSFB)

– BBB & B-CSF-B exist between the blood & brain interstitial fluid and CSF respectively to uniquely limit the exchange of substances into the brain. That is why the constituents of CSF are not the same as in ECFs (extracellular fluids) elsewhere in body.

–  These barriers exist both at the choroid plexus [between choroid epithelium (CSF) and capillary endothelium (blood)] and at tissue capillary membranes. The cause of low permeability is presence of tight junctions b/w the adjacent endothelial cells.

–  Because of the sensitivity of cortical neurons to even minor variations of ionic (K⁺, Ca⁺⁺,Mg⁺⁺,I-1⁺ etc) concentration changes, BBB is an additional defence evolved to protect & maintain the constancy of environment of neurons in CNS. It also protects brain from endogenous & exogenous toxins in the blood & prevents escape of neurotransmitters in general circulation. BBB is immature at birth and is breached (broken down) in areas of injury, infection and tumors. Tumors develop new capillary that lack light junction and contact with astrocyte – so the radioactive iodine labeled albumin penetrates tumor rapidly, making it stand out as an island of radioactivity in the surrounding normal brain. BBB is temporarily disrupted by sudden marked increase in BP or by IV injection of hypertonc fluids. Blood-CSF Barrier & Blood-Brain Barriers are highly permeable to water, CO₂ (carbondioxide), 0₂ (oxygen)₂, and most lipid soluble (lipophilic) substances such as free forms of steroid hormones, alcohol and anestheticsQ; slightly permeable to electrolytes like Na. (sodium), K⁺ (potassium) and Ck (chloride); and almost totally impermeable to plasma proteins, protein bound forms of steroid hormones, protein antibodies and most non lipid soluble large organic molecules (i.e. impermeable to, in general, all proteins and polypeptides)Q. It slows penetration of some smaller molecules like urea.

–                        Passive diffusion across cerebral capillaries with tight junction is very limited but numerous carrier-mediated & active transport system move substances out (more freely) as well as into the brain. Many peptide & drugs actually cross the cerebral capillaries but are transported back rapidly into blood by a multidrug nonspecific, p-glycoprotein – ATP binding transporter in apical membranes of endothelial cells, that transports various proteins & lipids across cell membranes. So larger (adequate) amounts of chemotherapeutic drugs, analgesics & opioid can be delivered to brain by inhibiting this transporter.

– Transporter exist for glucose, thyroid hormone, leptin hormone (control appetite & sympathetic activity) choline, several organic acids, nucleic acid precursors and basic, neutral and acidic aminoacids at BBB. Diffusion of glucose (the ultimate source of energy for nerve cells) across BBB would be very slow in absence of glucose transporters like GLUT 1. Two isoforms GLUT 1 (55 K) of brain capillaries/endothelium and GLUT 1 (45 K) of astroglia, neuron (+ GLUT-3) & microglia (+ GLUT-5) are encoded by a same gene, but they differ in the extent of glycosylation. Infants with congenital low GLUTI develop low CSF glucose concentrations in the presence of normal plasma glucose

l/t seizures and delayed development.

B i.e. Subfornical organ

A i.e. Tight endothelial function

Ans. is ‘b’ i.e., Neurohypophysis