Blood Brain Barrier Structure Function And Disease Biology Essay


As we all know, the blood brain barrier's main function is to regulate the diffusion of solutes between the central nervous system and the blood. Not only does it inhibit the passage of blood proteins into the central nervous system, but it also regulates the diffusion of vitamins, peptides, minerals, nutrients, free fatty acids, electrolytes and regulatory proteins in both the blood to brain and the brain to blood directions. The blood brain barrier does these things through several saturable and unsaturable mechanisms, such as tight junctions, that help in maintaining homeostasis. If these mechanisms where altered, especially the tight junctions, they lead to the alteration of the blood brain barrier function, which in turn leads to several health problems. In this paper, we will talk about the effect of hypoxia/ischemia, inflammation and other insults and how they affect the blood brain barrier and what they lead to. (William S. Banks, 1999; Brian T. Hawkins and Thomas P. Davis, 2005)

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Blood brain barrier is found at the level of cerebral micro-vascular endothelium to be a selective diffusion barrier with no openings on its membrane. The diffusion in blood brain barrier occurs due to tight junctions formed between cells on its membrane. (Oldendorf et al.., 1977)

Tight junction proteins are vulnerable to changes in expression, subcellular position, protein to protein communication and modification after translation, under both pathophysiological and physiological states (Huber et al., 2001) before proteins of tight junctions were well understood, it was confirmed that low calcium concentration on the outer membrane and high calcium concentration inside the cell could lead the blood brain barrier tight junctions to be destroyed through decreased expression and/or altered protein-protein interactions, which reveals that intracellular stores have a role in regulating tight junctions. (Naggy et al., 1985; Abbott and Reveset, 1991)

Malfunction of the blood brain barrier is a serious event in the developmental progression of several illnesses that can alter the central nervous system. In few cases, high levels of blood brain barrier permeability is a result of the pathology, such as ischemic stroke (Ilzecka, 1996) and traumatized brain (Morganti Kossmann et al., 2002) but in other cases such as in the presence of multiple sclerosis, the blood brain barrier permeability is considered to be a precipitating event (de Vries and Dijkstra, 2004). In other cases in which cerebrovascular abnormalities have been seen taking Alzheimer's disease as an example, the relationship between blood brain barrier destruction and pathology is still not well understood (Wardlaw et al., 2003)

As we said before, in this paper we'll talk about how some health problems affect the blood brain barrier that in turn affects the brain, central nervous system and the body. Cerebral ischemia is first on our list. Cerebral ischemia is a highly complicated health issue that is accompanied by a loss of blood flow as well as the lack of oxygen and important minerals, and it was also noted in several studies that cerebral ischemia is associated with increased levels of microvascular permeability. Several studies, using in vitro models of blood brain barrier, revealed that hypoxia and hypoxia/reoxygenation caused noticeable increasing levels of permeability and/or of blood brain barrier tight junctions being destroyed, even though during stress resulting from hypoxia could possibly increase permeability through transcellular pathways as well. A number of studies stated that hypoxic reorganisation of blood brain barrier tight junction seemed to be controlled partially by vascular endothelial growth factor. Vascular endothelial growth factor opposing forces lead to the reduction of oedema after an episode of ischemia and injury in vivo, leading to the conclusion that tight junction destruction is associated with the development and progression of ischemic brain injury. (Mark and Davis, 2002; Van Bruggen et al., 1999)

Second health issue on our list is inflammation. Inflammatory intermediates are known adjusters of blood brain barrier permeability. Therefore, if the blood brain tight junction permeability was altered, this leads us to think of neuroinflammatory disease states. Blood brain barrier tight junction alteration have been noted as an early symptom in the progression of multiple sclerosis, using MRI reports pointing out a compromised barrier prior to clinical symptoms. In laboratory models of multiple sclerosis, blood brain barrier destruction is initiated by T-cells and monocytes. (Morrissery et al., 1996) T-cells and monocytes are part of the an old patient if there was a malfunction in the immune-system, this can lead T-cells and monocytes for example to attack the body's tissue rather than fighting off viruses and bacteria. When this happens in the brain, the immune system cells, called neuro-specific auto-antibodies attack the blood brain barrier, which leads o these auto-antibodies entering the brain and binding to specific receptors which in turn lead to the death of these cells. This process is known to cause Alzheimer's disease. (Carol Turkington and Deborah Mitchell, 2009)

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The third subject on our list is identified as "other insults". Other insults include drugs such as cocaine and nicotine. The blood brain barrier can be affected by drugs of abuse. We take cocaine for example; cocaine has the ability to speed up the progression of HIV-associated dementia, a procedure that can involve both direct effects of cocaine on the endothelium as well as the ability to cause or lead to inflammatory effects. Nicotine, a drug that possibly has the power exert an effect upon the calibre of blood vessels, interrupts the diffusion of glucose, and ions at the blood brain barrier. Nicotine can also lead to an increased permeability in blood brain barrier especially to sucrose. The increased permeability to sucrose can lead to an ischemic stroke, which is also a risk factor in the case of diabetes. Diabetes is also known to lead to increased permeability in the retina's microvasculature as well as at the blood brain barrier. This increased permeability of sucrose as well as diabetes can aid in the progression of tumours in the brain. (Chehade et al., 2002; Goldstein et al., 2001)

From what has preceded, we can see the importance of blood brain barrier and blood brain barrier tight junctions in maintaining a healthy state of the brain and the body. The blood brain barrier controls the passage of lots of ions minerals vitamins etc... And when its function is altered due to disease or drug abuse, this will lead to the alteration of the homeostasis; this alteration will lead the subject to be prone to brain tumours, Alzheimer, multiple sclerosis and lots of other diseases, viruses and bacteria.