Gastroduodenal lesions and non-steroidal anti-inflammatory agents. What role does Helicobacter pylori play in this relationship?

In order to elucidate the mechanisms of release of EAAs and their excitotoxicity in cerebral contusion, cortical contusion was produced in the rat parietal cortex, and the changes in extracellular levels of EAAs in the central and peripheral areas of contusion were investigated using microdialysis. The cortical contusion induced a rapid increase in dialysate concentration of glutamate (Glu]d) from a baseline level of 4.6+/-2.8 microM to a maximum level of 36.3+/-12.8 microM. This elevation of glutamate was significantly attenuated by mild hypothermia (32 degrees C for 90 min, comprising 20 min before and 70 min after the injury induction) in the peripheral area of contusion (p < 0.01) but not in the central area. Histological evaluations revealed that the hypothermia reduced the necrosis volume of contusion to 38.3% of that in the normothermic control (p < 0.01). In situ administration of Co2+, an inhibitor of Co2+-dependent exocytotic release of EAAs from the nerve terminals, via the microdialysis system, also attenuated the Glu]d elevation following cortical contusion, in the peripheral area of contusion (p < 0.01) but not in the central area. These findings indicate that cerebral contusion involves heterogeneous and complex mechanisms of EAA release into the extracellular space. The release of EAAs in the contusion core was nonsensitive to hypothermia and Co2+ administration, suggesting that such EAA release was related to primary disruption of the cell membrane or vascular wall by the physical force of the head trauma, resulting in leakage of EAAs from the metabolic pool in the cytosole or blood stream. In contrast, in the peripheral area, the effectiveness of hypothermia and Co2+ administration implied a presynaptic mechanism of EAA release, which consisted, at least in part, of Ca2+-dependent exocytotic EAA release from depolarized nerve terminals. The EAAs released in the contusion core may diffuse towards a peripheral direction and act on the postsynaptic receptors, causing neuronal depolarization. Such a diffusion-reaction process appears to induce additional release of EAAs from the depolarized nerve terminals. Hypothermia may block this diffusion-reaction process and eventually reduce the contusion volume.