Biochemical pathogenesis of post-traumatic epilepsy

Head trauma is often followed by epilepsy and may be related to the breakdown of red blood cells and hemoglobin within the CNS. Injection of hemoglobin or iron salts into the rat cortex is known to induce a chronic epileptic focus. We observed the formation of superoxide anion (O₂) and hydroxyl radical (·OH) after ferric chloride injection into the rat cerebral cortex and suggest that these radicals, especially ·OH, may be responsible for the initiation of lipid peroxidation in neuronal membranes and for the accelerated production of guanidine compounds in the brain, which may in turn lead to epileptogenicity. Then, we found that treatment with epigallocatechin (EGC) or a phosphate diester of vitamins E and C (EPC), which are potent ·OH scavengers, significantly inhibited the formation of malondialdehyde and epileptic discharges in the iron-induced epileptic focus. This study was supported by a grant-in-aid for scientific research from the Japanese Ministry of Education, Science, and Culture.     

Acute restraint stress enhances calcium mobilization and proliferative response in splenic lymphocytes from mice

Calcium (Ca2+ ) plays an essential role in lymphocyte activation and maturation. Acute and chronic stress has been shown to modulate the lymphocyte immune response; but the relationship between cytosolic free Ca2+ concentration ([Ca2+ ]i) and the immune response in lymphocytes following exposure to stress has not been examined. In the present study, we investigated the effects of acute restraint stress on [Ca2+ ]i and the proliferation of splenic lymphocytes from mice. We observed that 2 h of restraint significantly increased plasma corticosterone levels in mice. On examining [Ca2+ ]i and the proliferation ex vivo of splenic lymphocytes isolated from restraint-stressed mice using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively, we found that acute restraint stress caused a significant increase in resting [Ca2+ ]i and significantly enhanced the ability of concanavalin A (Con A; a T-cell-selective mitogen) to increase [Ca2+ ]i but not that of lipopolysaccharide (LPS; a B-cell-selective mitogen). In addition, acute restraint stress significantly enhanced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Overall, there was a positive correlation between [Ca2+ ]i and T-cell proliferation following acute restraint stress. The enhancements of [Ca2+ ]i and T-cell proliferation were completely suppressed by verapamil (a Ca2+ channel blocker). These results suggest that acute restraint stress enhances Con A-stimulated T-cell proliferation by increasing [Ca2+ ]i via stimulation of Ca2+ entry.