Blood Brain Barrier, Kernicterus, Cerebral Circulation and Hydrocephalus Notes

BLOOD BRAIN BARRIER (BBB)

• Formed by CNS capillary endothelial cells, their intercellular junctions, and a relative lack of vesicular transport.
• Function: restricts the movement of large molecules and highly charged ions from entering the brain and spinal cord; requires a special carrier-mediated transport system.
• Substances that can penetrate the BBB: water, $CO<em>2$, $O</em>2$, the free form of a few steroid hormones, and some lipid-soluble substances.
• Glucose can cross the BBB very slowly; requires GLUT-1.
• Role of p-glycoprotein: a non-specific transporter protein in the BBB that protects the brain from harmful substances; its efficacy decreases with age. It is a multi-drug resistance (MDR) protein that transports drugs or peptides back to the blood after they have crossed cerebral capillaries.
  • Applied: Inhibitors of P-glycoprotein are used in chemotherapy.
• Circumventricular organs and their importance: areas of the brain that lack the BBB.
  • Examples: posterior pituitary, area postrema, OVLT, etc.
  • These organs are isolated from the rest of the brain by special ependymal cells known as Tanycytes.

Molecular Passageways and Transport Mechanisms Across the BBB

• Diagram illustrating the structure of the BBB components:
  • Endothelial cells with tight junctions
  • Basal lamina
  • Astrocytes
  • Pericytes
• Transport mechanisms:
  • Passive transport
  • Carrier-mediated transport
  • Efflux transport
  • Receptor-mediated transport
  • Adsorptive-mediated transcytosis

Applied Aspects of Circumventricular Organs

1. Chemoreceptor zone: triggers vomiting.
2. Angiotensin-II acts at OVLT: increases water intake.
3. Neurohemal organs: neurohormones/polypeptides enter circulation from here.

APPLIED ASPECTS OF B.B.B - KERNICTERUS

• Also known as Bilirubin Encephalopathy.
• The BBB is immature at birth; therefore, increased unconjugated bilirubin (which is lipid-soluble, unlike conjugated bilirubin, which is water-soluble) can enter and damage the brain, particularly the Basal Ganglia.
• Occurs when unconjugated bilirubin exceeds 25 mg/dl.
• Occurs when jaundice develops within 24 hours of birth (pathological jaundice).
• Causes:
  • Increased production of bilirubin: hemolysis, polycythemia, birth injuries.
  • Decreased excretion: hypoalbuminemia, breast milk jaundice, hereditary conjugation defects, obstruction in the biliary system.

Pathophysiology of Kernicterus

• Bilirubin attaches to cell membranes and is toxic to neurons and oligodendroglia.
• It damages the mitochondria, inhibits oxidative phosphorylation, and causes calcium release, promoting apoptosis.
• It also affects axonal and dendritic growth in the central nervous system.

Symptoms of Acute Bilirubin Encephalopathy

• Weakness, lethargy, and poor feeding.
• Extensor hypertonia, retrocollis, opisthotonus are generally seen in this phase.
• Hypotonia is typically seen in infants aged more than one week.

Symptoms of Chronic Bilirubin Encephalopathy

• Hypotonia
• Hyperreflexia
• Delayed achievement of milestones
• Visual and auditory defects
• Choreathetoid cerebral palsy
• The abdominal examination might show hepatomegaly or splenomegaly indicative of a hemolytic cause.

Investigations for Kernicterus

• S.Bilirubin (Serum Bilirubin), CBC (Complete Blood Count), Reticulocyte count, etc.
• Imaging studies are also done.

Treatment for Kernicterus

• Exchange transfusion
• Phototherapy
• I/V Ig (Intravenous Immunoglobulin)

Jaundice

• Yellowing of eyes
• Yellowing of skin
• Excess bilirubin in the blood
• Can lead to Kernicterus

Applied Aspects Regarding Cerebral Circulation

• Surgery at the base of the brain carries the risk of damaging the Circle of Willis and intervening critical structures like the Pituitary gland (during repair of aneurysm).
• Optic chiasm (surgeries for anterior-middle Circle of Willis).
• CN-3 & CN-4 damage (procedures near the posterior Circle of Willis).
• The connection between the anterior & posterior Circle of Willis is not only important for the perfusion of the brain but is also an important site for aneurysm (headache, 3rd nerve palsy, distal ischemia).
• Subclavian steal: stenosis or occlusion of the subclavian artery proximal to the vertebral artery, producing symptoms of posterior circulation ischemia (vertigo, ataxia, precipitated by exercise of the upper limb supplied by a stenotic subclavian artery).
• Moyamoya disease: distal stenosis of bilateral Internal Carotid Artery (ICA) giving rise to the development of collaterals which appear as 'puff of smoke' in angiography (Japanese meaning of moyamoya).
• Changes in regional circulation are seen in:
  • Huntington's disease (decreased flow to the caudate nucleus).
  • Alzheimer's disease (decreased blood flow to the superior parietal & frontal cortex).
  • Epileptic seizures, manic disorders, schizophrenia - reduction in blood flow to various parts of the cerebrum.

Hydrocephalus

Types of Hydrocephalus

1. Congenital: due to a complex mix of genetic & environmental factors during fetal development.
   • Causes: aqueductal stenosis (most common cause).
   • Neural Tube Defect (NTD): open NTD is known as Spina Bifida or myelocoele.
2. Acquired: develops after birth due to trauma or neurological condition of the brain like meningitis, brain tumors, head injury, intraventricular hemorrhage (i/v hg), tuberculosis.
3. Compensated or Arrested: Hydrocephalus is present at birth, but after treatment, it is stable & asymptomatic for many years.
4. Communicating / External: Flow of CSF is blocked as it exits from the ventricles.
   • Occurs due to thickening of the arachnoid at the base of the brain, which blocks CSF flow from spinal to cortical subarachnoid spaces.
   • CSF can still flow between ventricles.
   • Surgical intervention is not mandatory.
5. Non-Communicating/Internal: also known as Obstructive Hydrocephalus.
   • CSF is blocked along one or more passages connecting ventricles & remains stuck within ventricles.
   • The most common cause is aqueductal stenosis.
   • Surgical intervention needed - 3rd ventriculostomy.

Grading of Hydrocephalus and Associated Symptoms

• EOM = extraocular muscle.