Rick,
You may be familiar with this example of wartime stress increasing the permeability of the BBB in Israeli soldiers.
Doc
sulcus.berkeley.edu
STRESS AND THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER
Category: Neurochemistry
Term Paper Code: 146
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The blood-brain barrier (BBB) is the biological barrier that protects the brain by regulating the flow of numerous substances into the brain. These substances can range from the rapidly circulating ions to neurotransmitters, growth factors, bacteria and their toxins, and other substances that can affect the central nervous system. What do go through the BBB are the small hydrophobic or lipophilic, non-ionic, and non-polar molecules, because they can cross or diffuse into the membrane more easily. The BBB consists of a continuous layer of endothelial cells that are joined by tight junctions with very high electrical resistance (Hanin 1996). This concept of the BBB was first introduced by a famous bacteriologist named Paul Ehrlich, when he demonstrated that intravenously infected dyes stained most organs in the body, but the brain remained unstained (Hanin 1996).
However, the BBB is not as a rigid, non-flexible barrier like the Wall Berlin as what people usually associate the word “barrier” with. It is the permeability of the BBB that governs the “traffic flow” of the substances that go in and out of the brain, and therefore, there is no definite set of substances that always can or cannot cross the BBB. A very interesting phenomenon was introduced in MCB 165 course regarding this permeability of the BBB. Citing the work of Friedman (1996), Prof. Presti suggested that the soldiers who had participated in the Gulf War might have had some penetration of the substance pyridostigmine into their brains, when it was administered to the soldiers as a pretreatment against soman poisoning. Soman is an organophsphate nerve gas routinely used in Western armies, which can inhibit acetylcholinesterase in the peripheral nervous system to cause abnormal parasympathetic functions. Pyridostigmine also inhibits acetylcholinesterase, but due to its quaternary ammonium group, it cannot cross the BBB under the normal condition. What that means is that, at best, it can only exert its effect on the peripheral nervous system in the forms of diarrhea, excess sweating and increased salivation. This is the very reason why pyridostigmine is commonly used as a pretreatment against acetylcholinesterase-inhibiting nerve gases. Also, thousands of people are taking pyridostigmine safely everyday as a treatment for chronic neuromusclular disorder called myasthenia gravis, because the side-effect of pyridostigmine is minimal compared to the severe symptoms that the disease causes. However, the findings of the Israeli scholars, Sharabi et al. (1991), report a threefold increase in the frequency of central nervous system symptoms (headaches, insomnia, drowsiness, nervousness, unfocused attention, and impaired capacity to conduct simple calculations) following pyridostigmine ingestion by 213 Israeli soldiers treated during the Persian Gulf War. This clearly indicates that there must have been some penetration of pyridostigmine through the BBB. Friedman (1996) suggests a promising explanation to this possible penetration by demonstrating that stress causes changes in the permeability of the BBB. Using mice in his experiment, Friedman found out that those mice that were subject to forced swimming (a known stressed condition) reduced the pyridostigmine dose required to inhibit mouse brain acetylcholinesterase activity by 50% to less than 1/100th of the usual dose. Hence, there seems to be a significant correlation between stress and the permeability of pyridostigmine into the central nervous system. From this, he concluded that peripherally acting drugs administered under stress may reach cross the BBB and affect centrally controlled functions.
I was very intrigued by this phenomenon when I read the article in the reader, and when it was presented in the lecture. It is in line with the current trend of various findings which suggest that stress is not an arbitrary, implicit, or exclusively emotional factor anymore, but a very important part of understanding human physiology. I have always wanted to see more research literature that makes some comprehensive approach to link what is commonly referred to as being “not scientific,” “taboo,” “subjective,” or “implicit” with empirical explanations. Saying “well, that’s just too subtle and since we cannot measure it, I won’t even make any attempt to describe it in terms of science- let’s forget it!” to subject matters like mind of spirituality is, I believe, just being idle on there jobs.
I, therefore, searched through literatures to find more related researches done on the topic of the relationship between stress and BBB. I have found many, and they all seem to support Friedman’s conclusion.
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