Effects of amantadine and topiramate on neuronal damage in rats with experimental cerebral ischemia-reperfusion

Abstract

Background. Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia.Objectives. To investigate the effects of amantadine and topiramate on apoptosis and cellular oxidative damage. Materials and methods.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.Results. 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.Conclusions. 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.

Protective effect of basic helix-loop-helix family member e40 on cerebral ischemia/reperfusion injury: Inhibition of apoptosis via repressing the transcription of pleckstrin homology-like domain family A, member 1

“…37 Previous study suggests that amantadine and topiramate can improve I/R injury by reducing apoptosis. 38 We found that the protein accumulation of cleaved caspase-3, cleaved PARP and BAX was enhanced in ODG/R-induced neurons, while BHLHE40 overexpression reduced the protein amount, indicating that BHLHE40 exerted an anti-apoptotic role in I/R injury.…”

The protective effects of topiramate and spirulina against doxorubicin-induced cardiotoxicity in rats

“…76 Furthermore, previous studies conducted on rats have demonstrated the antiapoptotic activity of TPM against methylphenidate-induced neurotoxicity and cerebral ischemia/reperfusion neuronal damage. 18,77 However, the effect of TPM on preventing apoptosis in cardiotoxicity models is still understudied and requires further investigation, including the assessment of other apoptotic and anti-apoptotic markers.…”

“…17 Furthermore, several studies have suggested that TPM possesses antioxidant, anti-inflammatory, and antiapoptotic properties, making it a potential protective agent against diseases characterized by inflammation and oxidative stress. 18,19…”

“…17 Furthermore, several studies have suggested that TPM possesses antioxidant, anti-inflammatory, and antiapoptotic properties, making it a potential protective agent against diseases characterized by inflammation and oxidative stress. 18,19 Spirulina (SP), a spiral filamentous blue-green alga, 20 is rich in essential amino acids, vitamins, and phytochemicals such as carotenoids, polyphenols, and phycocyanin. 21 Due to its richness in many bioactive elements, SP exhibits antioxidant, anti-inflammatory, and antiapoptotic activities.…”