Blood-brain barrier

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It has long been recognised that the blood-CSF barrier is complementary to the blood-CNS barrier, usually termed the blood brain barrier. This results often in a chemical gradient between small molecule concentration in the blood and the CNS extracellular fluid (ECF), most easily evaluated by examining the cerebrospinal fluid, but brain ECF is not quite the same as CSF. Anatomically this is explained by there being at a minimum, an endothelial cell layer between the blood and the CNS ECF. In the case of the CSF, the specific model of the endothelium of the choroid plexus is well understood, if more complex than the simple barrier model used up until the 1990s.

Contents

Physiology

It is believed that the brain microvascular endothelial cells by way of tight junctions, basement membrane and other structural design and metabolic barriers such as intracellular enzymes and transport systems have evolved to ensure:

  1. Homeostasis of the neuronal "milieu" optimising function of:
  2. Neurotoxins that are present in the blood are minimized in the extracellular fluid around CNS neurons.

Astrocytes, pericytes, microglia and even neurons may be involved in this process as well. For example, in mammals astrocytic end-feet tightly ensheath blood vessel walls and while they appear to be critical for the induction and maintenance of the endothelial tight junction barrier, they are not actually the functional element of the blood brain barrier.

Active transport

The active transport mechanisms include:

  • Endothelial cell vesicles or caveolae[1] serving as mini-transporters of fluid substances.
    • These can change as a result of cerebral injury and ultrastructurally look more like tunnels and canals than isolated vesicles consistent with more permeability
  • Adhesion molecules
    • These may facilitate the movement of leukocytes, neoplastic cells and human pathogens across the barrier

Disruption of blood brain barrier

The blood brain barrier is certainly not absolute with good evidence that its absolute degree is less with age in man for some substances[2]. Indeed some think this is more associated with elevated serum gonadotropins[3]. Stress or disease can modify it with in particular several proinflammatory substances (perhaps sometimes acting through corticotropin releasing hormone and mast cells), and specific disease-associated proteins being known to mediate such dysfunction:

References

  1. Lossinsky AS, Shivers RR. Structural pathways for macromolecular and cellular transport across the blood-brain barrier during inflammatory conditions. Review. Histology and histopathology. 2004 Apr; 19(2):535-64.
  2. Pakulski C, Drobnik L, Millo B. Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier. Medical science monitor : international medical journal of experimental and clinical research. 2000 Mar-Apr; 6(2):314-8.
  3. Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica et biophysica acta. 2008 Jun; 1782(6):401-7.(Link to article – subscription may be required.)
  4. Bowler JV. Blood-brain barrier permeability in type II diabetes. Journal of neurology, neurosurgery, and psychiatry. 2003 Jan; 74(1):6.
  5. Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD. Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Diabetologia. 2007 Jan; 50(1):202-11.(Link to article – subscription may be required.)
  6. Donahue JE, Johanson CE. Apolipoprotein E, amyloid-beta, and blood-brain barrier permeability in Alzheimer disease. Journal of neuropathology and experimental neurology. 2008 Apr; 67(4):261-70.(Link to article – subscription may be required.)
  7. Deane R, Zlokovic BV. Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease. Current Alzheimer research. 2007 Apr; 4(2):191-7.
  8. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2006 Sep; 1(3):223-36.(Link to article – subscription may be required.)
  9. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2006 Sep; 1(3):223-36.(Link to article – subscription may be required.)
  10. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2006 Sep; 1(3):223-36.(Link to article – subscription may be required.)
  11. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2006 Sep; 1(3):223-36.(Link to article – subscription may be required.)
  12. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2006 Sep; 1(3):223-36.(Link to article – subscription may be required.)
  13. Sharma HS, Johanson CE. Blood-cerebrospinal fluid barrier in hyperthermia. Progress in brain research. 2007; 162:459-78.(Link to article – subscription may be required.)
  14. Oztaş B, Akgül S, Arslan FB. Influence of surgical pain stress on the blood-brain barrier permeability in rats. Life sciences. 2004 Mar 5; 74(16):1973-9.(Link to article – subscription may be required.)

This article is a work in progress. Please feel free to contribute to it.

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