The Study Of The Neuroprotective Effects And Related Mechanisms Of Gastrodin During Cerebral Ischemia

Ischemic stroke is a leading cause of death and disability worldwide, and it's related to a transient or permanent reduction in cerebral blood flow. Many studiesshown that ischemic brain damage is resulted from multiple factors such as changes of neurotransmitters, tissue acidosis, production of free radicals, an ion balance disorder, lipid peroxidation, apoptosis and inflammation. Drugs treatment is one of the most important therapeutic methods of ischemic diseases. There are many active substances with anti-brain ischemia physiological activity in natural products. So looking for the active substances from natural products is important for the exploitation of new drugs.Gastrodia elata Blume (Orchidaceae) has been used in traditional Chinese medicine for centuries to cure dizziness, epilepsy, stroke and dementia. A primary component of the most functional extracts from the rhizome of Gastrodia elata is gastrodin. It has been reported that gastrodin can decrease mortality rate resulting from ischemia in mice and it possesses protective effects against cerebral cortex neuron or astrocyte damage induced by simulated cerebral ischemia and reperfusion in vitro. However, the mechanisms underlying the protective effects of gastrodin on cerebral ischemia are currently unclear.In the present study, we studied the effects of gastrodin on cerebral ischemic injury in rats caused by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD)-induced injury in vitro. By using microdialysis and HPLC te.chniques, the effect of gastrodin on changes in neurotransmitters was also measured during ischemia/reperfusion in rat hippocampus. The results showed that the gastrodin markedly reduced OGD and MCAO-induced neuronal injury, inhibited the OGD-induced Ca²⁺ and NO increase. Gastrodin treatment also significantly inhibited elevation of glutamate while increased the GABA level in rat hippocampus during the postischemic period. This data has verified the hypothesis that gastrodin is in favor of neuroprotective effects against injury induced by brain ischemia.In addition, to assay the cellular metabolic activity after using the acid extracellular solution to induce the damage of the primary hippocampal neurons, the methods of the cellular acidosis model based on the primary hippocampal neurons were established. And then we investigate the mechanisms of acidosis damage on hippocampal neurons by studying the changes of skeleton protein F-actin, intracellular Ca²⁺ concentrations, reactive oxygen species (ROS) production, necrosis and apoptosis. We also put the methods forward to appraise the effects of gastrodin. From these appraisements, we can also prove the validness of the acidosis model and systematically study the mechanism of gastrodin as well. The results showed that gastrodin significantly inhibited the neuronal injury induced by acidosis. Meanwhile, the present study also indicates that it is correct and valid for the cellular acidosis model to screen and appraise the anti-stroke agents.Based on above results, it is reasonable to draw conclusion as below: Firstly, gastrodin ameliorated cerebral ischemic damage through inhibiting glutamate release, Ca²⁺ overload and production of NO. Secondly, gastrodin inhibited the cellular injury by decreasing of Ca²⁺ overburden, ROS production, cellular edema and skeleton ruin induced by acidosis. Finally, it is correct and valid for the cellular acidosis model to screen and appraise the anti-stroke agents.In summary, the present study synthetically explored the neuroprotective effects of gastrodin for the first time, and established an acidosis-based screen method based on the pathological mechanism of brain ischemia. Our studies provide an impetus for novel therapeutictargets and would be helpful to related drug screening, exploitation and mechanism investigation.