Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

Abstract

Background and Purpose:This study aimed to investigate the effect of ceftriaxone on oxidative stress and gap junction protein (connexin 43, Cx-43) expression in pentylenetetrazole (PTZ) induced kindling model.Methods:Twenty four Sprague dawely rats were divided into 3 equal groups (a) normal group: normal rats. (b) PTZ kindled group: received PTZ at the dose of 50 mg/kg via intraperitoneal injection (i.p.) every other day for 2 weeks (c) ceftriaxone treated group: received ceftriaxone at the dose 200 mg\kg/12 hrs via i.p. injection daily from the 6th dose of PTZ for 3 days. Racine score, latency before beginning the first myoclonic jerk and duration of the jerks used as parameters of behavioral assessment. Immunohistopathological study for Cx-43 expression in hippocampus and measurement of markers of oxidative stress (malondialdehyde [MDA], low reduced glutathione [GSH] and catalase [CAT]) in hippocampal neurons were done.Results:PTZ kindling was associated with behavioral changes (in the form high stage of Racine score, long seizure duration and short latency for the first jerk), enhanced oxidative stress state (as demonstrated by high MDA, low GSH and CAT) and up regulation of Cx43 in hippocampal regions. While, ceftriaxone treatment ameliorated, significantly, PTZ-induced convulsions and caused significant improvement in oxidative stress markers and Cx-43 expression in hippocamal regions (p < 0.05).Conclusions:These findings support the anticonvulsive effects of some beta-lactams antibiotics which could offer a possible contributor in the basic treatment of temporal lobe epilepsy. This effect might be due to reduction of oxidative stress and Cx43 expression.

Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review

“…A similar study also showed that CEF treatment substantially improved PTZ-induced convulsions and caused a noticeable modulation of oxidative stress indicators and Connexin 43 expression in the CA3 region of the hippocampal area. CEF also prominently reduced tonic-clonic convulsions and duration of these convulsions and prolonged the latency time in the PTZkindling model (Hussein et al, 2016).…”

Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via Nrf2/ARE Signaling

“…Bolkvadze et al reported that in the PTZ test, the latency to the first seizure in mice with hippocampal damage was reduced compared with the mice without damage [37]. Hussein et al demonstrated that PTZ kindling was associated with behavioral changes, which were in the form high stage of Racine score, long seizure duration and short latency for the first jerk [38]. Our results found that Rb1 dose-dependently reduced PTZ-induced seizure duration and prolonged seizure latency, suggesting Rb1 can suppress the severity of PTZ-induced seizures.…”

Hippocampal and Cerebellar Changes in Acute Restraint Stress and the Impact of Pretreatment with Ceftriaxone

“…The effect of ceftriaxone on improving behavior, cognition, and depression in the current study can be explained by the fact that ceftriaxone and corticosterone modulate specific frequency bands in opposite directions, and reveals the potential role of ceftriaxone in counteracting the effects of corticosterone [40]. Ceftriaxone might have attenuated oxidative stress markers in the hippocampus and upregulated the transporter of glutamate-1 [41], resulting in a reduction in the overload of glutamate and calcium involved in the production of reactive oxygen species (ROS) in the hippocampus [42]. This is confirmed in the current study by the effect of ceftriaxone on the expression of GLT1.…”