Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture

Abstract

Epilepsy is a common brain disorder that seizures could cause neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of this way. The aim of this study was to investigate the neuroprotective effect of astaxanthin (ATX), on pentylenetetrazole (PTZ) induced epileptic seizures in rats and in SH-SY5Y human neuroblastoma cell culture. Method: In our study, we used 42 male 230-250 g Wistar Albino rats. Animals were divided into seven groups as control, saline (PTZ; 1 ml/kg serum physiologic), positive control (2,5 mg/kg diazepam), 10 mg/kg, 20 mg/kg, 40 mg/kg and 80 mg/kg ATX for seven days. Thirty min after the administration of the last drug at the indicated doses, PTZ was administered 45 mg/kg to induce an epileptic seizure. The animals were observed for 30 min. Seizure stages according to the Racine Scale (RC) and first myoclonic jerk times (FMJ). Twenty four hours after PTZ injection, passive avoidance test was performed, and then brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis 1 (CA1), CA3 and dentate gyrus (DG) regions were evaluated histopathologically regarding neuronal damage. Besides, oxidative stress markers total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues. Furthermore, ATX was performed in vitro SH-SY5Y human neuroblastoma cell culture to evaluate PTZ-induced neurotoxicity. Results: When epileptic behaviors were evaluated, ATX did not affect RC and FMJ (p>0, 05). However, ATX reduced both cognitive impairment in passive avoidance test and neuronal damage in the hippocampus (p<0, 05). Moreover, ATX reduced both TOS levels and OSI in the brain (p<0, 05). Besides of these in vitro studies, ATX increased neuronal viability in vitro. Conclusions: Although ATX does not have antiepileptic properties directly, it has a protective effect on not only in vivo but also in vitro. These effects may occur by possible oxidative pathways.

Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

“…A positive effect on histopathological findings caused by PLC-induced kindling was demonstrated in group IV, i.e., those treated with L and SVP, and group V, where L was given alone. Essentially, regular pyramidal cell appearances were present on H× and E stained microscopy of CA1 and CA3 territories; the DG granular cell layer showed no attenuation, even displaying augmented width, and again, the microscopic assessment was within normal limits, consistent with previously published findings [ 8 , 31 ]. These workers concluded that in PTZ- and PLC-induced kindling, L has a neuroprotective action.…”

“…Enhanced neurogenesis, somatic hypertrophy, or reactive astrogliosis may contribute to the DG granule layer augmentation demonstrated in this work. Varying studies have supported these mechanisms [ 8 , 56 ].…”

“…However, only two-thirds of patients respond to such treatment, leaving a significant cohort potentially immune to conventional therapy, despite trials of varying drug regimes. Additionally, an adverse side effect profile is an issue with several currently employed AEDs [ 8 ]. Cerebral damage that may be initiated by SE is not prevented by drug use [ 9 ].…”

Involvement of H2S, NO and BDNF‐TrkB signalling pathway in the protective effects of simvastatin against pentylenetetrazole‐induced kindling and cognitive impairments in mice

“…They reported degeneration and necrosis in some neurons with gliosis in the cerebral cortex and degeneration of some Purkinje cells in the cerebellar cortex. Moreover, neuronal damage and surrounding gliosis in the hippocampal regions of PTZ‐treated rats were reported 40 . There is an association between seizures and histopathological changes in the brain as illustrated by several animal studies 41 .…”

“…Moreover, neuronal damage and surrounding gliosis in the hippocampal regions of PTZ-treated rats were reported. 40 There is an association between seizures and histopathological changes in the brain as illustrated by several animal studies. 41 It has been demonstrated that seizures may result in morphological alterations such as production of dark neurons and neuronal damage in the brain.…”