Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

Abstract

Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.

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

“…Histopathological studies of the hippocampus tissues indicated that epilepsy induced by PTZ caused an obvious decrease in the number of the normal neurons, as evidenced by a decrease in its Nissl granules content compared with normal group, which was in agreement with previous studies [48]. However, Rb1 administration in the present study displayed a decrease in hippocampal damage through a significant increase in the Nissl granules content of the normal neurons, indicating that Rb1 protects against PTZ-induced hippocampal neuron damage.…”

Effect of lamotrigine on epilepsy‐induced cognitive impairment and hippocampal neuronal apoptosis in pentylenetetrazole‐kindled animal model

“…Previous studies have suggested that LTG decreased seizure severity and hippocampal CA3 region damage in PTZ‐kindled animals (Haggag, Hasanin, Raafat, & Abdel, ). Unfortunately, we did not find this reduction in neuronal cell apoptosis in the hippocampal CA3 region both in LTG and VPA treated animals in our study, which is consistent with a study on LTG and VPA in a status epilepticus model of rat pups (Halbsgut, Fahim, Kapoor, Hong, & Friedman, ).…”

One-carbon cycle alterations induced by Dyrk1a dosage

“…Epilepsy is primarily caused by the inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Epileptogenesis induced by pentylenetetrazole (PTZ) caused a significant increase in serum hcy in comparison to control rats [32]. Unlüçerçi and colleagues [33] also reported increase of serum hcy levels in epilepsy.…”