Abstract
Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia. To investigate the effects of amantadine and topiramate on apoptosis and cellular oxidative damage. This experiment was performed using 30 male Wistar albino rats. The right internal carotid artery was identified and clamped with an aneurysm clip under general anesthesia, except for animals in the control group. After 10 min of occlusion, the aneurysm clip was removed, allowing reperfusion. After reperfusion and a waiting period of 12 h, the test and control groups were intraperitoneally administered the following solutions: the sham group received 10 mg/kg of isotonic solution, the amantadine group received 20 mg/kg of amantadine, the topiramate group received 40 mg/kg of topiramate, and the amantadine-topiramate group received 20 mg/kg of amantadine and 40 mg/kg of topiramate. After 24 h, the rats were euthanized. Apoptosis was evaluated using the TUNEL method. Total antioxidant status (TAS), total oxidant status (TOS), total thiol, and ischemia-modified albumin (IMA) levels were measured in both brain tissue and serum samples. The rate of apoptosis in the sham and amantadine groups increased significantly compared to the control group and the non-ischemic counter hemisphere. In the amantadine-topiramate group, both serum TAS and tissue thiol levels decreased. Tissue TOS levels were significantly higher in the topiramate group compared to all other test groups. Tissue TAS levels were significantly higher in the amantadine group compared to all other test groups. This experimental ischemia-reperfusion model revealed that topiramate reduces apoptosis in the early period after ischemia and that its combination with amantadine does not provide additional benefits against cell death. However, topiramate did not have an inhibitory effect on the oxidative stress biomarkers used in our study (TAS, TOS, IMA, and thiol). Studies that reveal the neuroprotective mechanism of action and long-term effects of topiramate are needed to complement this study.
Highlights
Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia
Total antioxidant status (TAS), total oxidant status (TOS), total thiol, and ischemia-modified albumin (IMA) levels were measured in both brain tissue and serum samples
This experimental ischemia-reperfusion model revealed that topiramate reduces apoptosis in the early period after ischemia and that its combination with amantadine does not provide additional benefits against cell death
Summary
Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia. Experimental stroke models are valuable because they can reveal important information about the biochemical and pathological changes that ischemia causes in cerebral tissue, and guide treatment options that act through these mechanisms. Ischemia triggers apoptosis in cerebral tissue, leading to apoptotic cell death. This involves 2 pathways: the intrinsic pathway, which is associated with mitochondrial release and caspase-3 stimulation of cytochrome c, and the extrinsic pathway, which leads to caspase-8 stimulation as a result of activation of cell surface death receptors. The developing ischemia destroys the cells that perform essential functions, such as oxygen transport, glucose production and maintenance of neuronal ionic gradients. It is thought that cytotoxic accumulation of intracellular Ca2+ initiates a series of cytoplasmic and nuclear events, which primarily trigger the intrinsic apoptotic pathway
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