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same surge after six hours time does not open the blood brain barrier. Injury may also cause the induction of ornithine decarboxylase activity by an unknown mechanism. The ornithine decarboxylase activity is increased twenty-fold. Ornithine is decarboxylated by ornithine decarboxylase to putrescine, which in turn is synthesized by spermidine synthase to spermidine and then by spermine synthase to spermine. These last two reactions require S-adenosylmethionine decarboxylase. Therefore, the induction of ornithine decarboxylase activity results in the accumulation of putrescine. The ornithine decarboxylase polyamine pathway is activated after cellular injury and its tight control is necessary for neuronal survival. Putrescine, spermidine and spermine are essential for normal cell growth, development and regeneration. After trauma, an accumulation of putrescine in the cerebral microvessels, this induces shrinkage in the endothelial cells and opening of the blood brain barrier causing vasogenic edema. Inhibiting ornithine decarboxylase by alpha difluoromethylornithine can block the accumulation of putrescine from ornithine. An experimental evidence adding putrescine prevents the protective effects of alpha difluoromethylornithine. Putrescine accumulates before edema. Ornithine decarboxylase messenger RNA is increased immediately after injury. (Henley, et. al., "Journal of Neurotrauma," 1996, 13:487-496.) Isoflurane increases putrescine and catamine decreased putrescine and spermidine. Ketamine also causes hyperglycemia and edema.
Other than mechanical disruption and ornithine, it is possible that leukotriene C4 leads to blood brain barrier breakdown and vasogenic edema, as well as bradykinin which opens the blood brain barrier when tumors are involved. Bradykinin does not open the blood brain barrier normally. Bradykinin works in about 15 minutes and causes increases in intracellular calcium and stimulates nitric oxide. Blood brain barrier breakdown may also be secondary to calcium influx and activation of the calcium calmodulin and calcium protein kinase C complex. Increasing the brain temperature to 41 degrees systemic also increases the blood brain barrier permeability. This can be stabilized by ketaserin, indomethacin and naloxone. Additionally arginine vasopressin increases vasogenic edema, there is an arginine vasopressin 1 receptor on microvessels. Neuronal nitric oxide synthetase also opens the blood brain barrier. With trauma there is leakage of albumin in humans when lactated ringers is used as a medium, but not with 7.5% saline, even though the HHS vasodilates there is no opening of the blood brain barrier. Total serum protein and albumin, as well as local concentrations of proteins and albumin, leak in vasogenic edema and determine the amount of vasogenic edema that takes place. HHS also increases cerebral perfusion pressure, decreases intracerebral pressure, decreases swelling and decreases tissue necrosis.
There are ways to preserve the blood brain barrier. Normally the blood brain barrier needs to be stabilized in cases of (Continued on page 49)
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