The Experimental Study On The Relationship Between Carbonic Anhydrase And Hyperbaric Oxygen-induced Convulsion

Hyperbaric oxygen-induced convulsion, which is also called convulsion type of oxygen toxicity, happens after the body exposed to oxygen of a partial pressure over 200 kPa (ATA) for a certain period of time. It has the symptoms that resemble the outbreak of epilepsy and so that it is named after this. Researchers have devoted to study oxygen toxicity for more than a century. Because of the difficulty of achieving the data from inside of the hyperbaric chamber and so on, the precise mechanisms of hyperoxia-induced seizures remain to be determined. Experimental results indicate that there are many factors taking part in the onset of hyperbaric oxygen-induced convulsion. Acetazolamide is a kind of specific inhibitor of carbonic anhydarase (CA). It can increase the cumulation of the endogenous carbon dioxide thus it is usually used as a tool drug to dilate brain arterioles. On the other hand, it is a drug that usually plays a role in the medication of epilepsy. And it presents good effect in clinic application usually. It is reported that acetazolamide can shorten the latency of hyperbaric oxygen-induced convulsion. Hyperbaric oxygen-induced convulsion resembles the epilepsy disease, and many anticonvulsant drugs can counterwork hyperbaric oxygen-induced convulsion. As a kind of medicine for epilepsy, acetazolamide, can not alleviate it, on the contrary, it aggravates the convulsion, why? In order to explore this issue, we determine the latency of hyperbaric oxygen-induced convulsion by methods of behavior observation and EEG inspection through intraperitoneally and introventricularly drug-administered ways. For the sake of studying the ways that acetazolamide influence the hyperbaric oxygen-indued convulsion, we measured the change of the maleic dialdehyde (MDA) dose and the activity of antioxidant enzymes including glutathione peroxidase (GSH-Px),glutathione reductase (GR) and catalyse (CAT) with chemical reagent. In order to determine the change of the expression of the glutamic acid decarboxylase, we measured the protein quantity with Western Blot technique. Through all of these experiments we try to survey if and how the dilation effect of endogeneous carbon dioxide works on the outset of hyperbaric-induced convulsion. All results are listed as follows:Influence of the activity of carbonic anhydrase on the latency of hyperbaric oxygen-induced convulsion The results indicate that acetazolamide can shorten the latency of hyperbaric oxygen-induced convulsion when it being administered to SD rats intraperitoneally more than 7.5 mg/kg body weight. And the more we inject it, the longer latency we gets. But when being pretreated with indomethacin 20 mg/kg body weight, the activator of carbonic anhydrase, before the acetazolamide injection, the latency of hyperbaric oxygen-induced convulsion gets back much. When being administered to SD rat introventricularly more than 0.5 μg, acetazolamide can prolong the latency of hyperbaric oxygen-induced convulsion significantly. The mechanism of CA activity change works on hyperbaric oxygen-induced convulsionThe effect of the CA activity change on the oxidation and the activity change of the antioxidant enzymes in brain induced by hyperbaric oxygen. The results show that: Compare with the control, MDA content in cortex increases significantly in NS 16 min group, as well as it does both in cortex and hippocampus of the acetazolamide 16 min group. The MDA content of cortex in acetazolamide 16 min group is more than it in the same exposure time course group of NS. MDA content of all groups correlates with the dose of acetazolamide and the exposure time closely. There was no significant difference between each two groups in the activity of GSH-Px, though it varied with the oxidation levels. In the cortex and hippocampus, the activity of GSH-Px boosted up at first, but with the progress of the oxidation it was impaired consequently. In the striatum, the activity of GSH-Px increased step by step with the aggravation of the oxidation. Compare with the...