Ceftriaxone Chronic Administration Can Upregulate Glutamate/Cysteine Anti-porter (xCT) and Reduce Seizure Severity in an Animal Model of Temporal Lobe Epilepsy
- سال انتشار: 1397
- محل انتشار: پانزدهمین کنگره بین المللی صرع ایران
- کد COI اختصاصی: EPILEPSEMED15_143
- زبان مقاله: انگلیسی
- تعداد مشاهده: 459
نویسندگان
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad
Department of Physiology, Faculty of Biology, Damghan University
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad
Department of Physiology, Faculty of Biology, Damghan University
چکیده
Background. Temporal Lobe Epilepsy (TLE) is one of the most common types of epilepsies that affect temporal lobe structures including hippocampus. Glutamate excitotoxicity can impair cognitive functions and induce neuroinflammation. Astrocytic Glutamate uptake can reduce these effects through glutamate transporters including GLT-1 and xCT. In this study the effect of Ceftriaxone, a pharmacological upregulator of GLT-1 on the level of xCT expression and seizure severity was assessed. Materials and Methods. 20 male rats were randomly (200-250 gr) divided into 4 groups: 1.Control group (N=5, animals received vehicle) 2. Pil group (N=5, animals received 30 mg/kg pilocarpine and Status Epilepticus (SE) was induced) 3. Pil+Cef group (N=5, animals received pilocarpine and daily administration of Ceftriaxone 200mg/kg for 5 days) 4. Cef group (N=5, animals only received 5 administration of Ceftriaxone). Animals were monitored for seizure activity during SE induction using Racine scale with minor modifications. 72 hours after SE induction, the hippocampus of the animals were extracted and the mRNA content was subjected to RT-qPCR for quantifying xCT expression (GAPDH as the reference gene). Data were analyzed using GraphPad Prism 7.0 software. Findings. Results show that Ceftriaxone treatment can significantly reduce seizure activity measured as Stage 3 and 4 seizure durations (P< 0.0001) and SE induced mortality (P< 0.05). It is also demonstrated that 72 hours following SE, xCT expression significantly decreases in Pil group (P< 0.01, compared to control). Ceftriaxone treatment can upregulate xCT in both Cef group (P< 0.0001, compared to control) and Pil+Cef group (P< 0.05, compared to Pil group). Conclusion. These results suggest that Ceftriaxone can reduce seizure severity and glutamate excitotoxicity induced by Temporal lobe epilepsy, probably through upregulation of glutamate transporters GLT-1 and xCT.کلیدواژه ها
Glutamate Excitotoxicity, xCT, GLT-1, Temporal lobe epilepsy, Ceftriaxoneاطلاعات بیشتر در مورد COI
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