Neuroprotective effects of vitamin D alone or in combination with lamotrigine against lithium-pilocarpine model of status epilepticus in rats

Abstract

Status epilepticus (SE) is considered one of the major serious forms of epilepsy with high mortality rate. Since the currently available antiepileptic drugs have low efficacy and high adverse effects, new more efficient and safe therapies are critically needed. There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic and therapeutic potential of vitamin D (vit-D) use in many neurological disorders. Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats. Rats were divided into five groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit-D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and lamotrigine for 2 weeks. At the end of treatment, SE was induced by single intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine (30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide), brain neurochemistry (γ-aminobutyric acid and glutamate), and brain histopathology have been evaluated. Vit-D prevented pilocarpine-induced behavioral impairments and oxidative stress in the brain; these results were improved in combination with lamotrigine. Vit-D has a promising antiepileptic, neuroprotective, and antioxidant effects. It can be provided to patients as a supportive treatment besides antiepileptic drugs. However, clinical trials are needed to establish its efficacy and safety.

Effects of Cerebrospinal Fluid AMPA Receptor Levels on the Clinical Efficacy of Lamotrigine in Epilepsy Treatment

“…LTG is a benzotriazine derivative, a currently novel broad-spectrum AED. The mechanism of LTG in controlling epilepsy includes inhibiting the release of glutamate and aspartic acid, followed by selective effects on Na + channels and blocking the binding of excitatory glutamate to its receptors [12] .…”

Impacts of Immune System in an Experimental Social Behavior Model: Review Article

“…Regarding the immunological parameters; it was reported that winners had a significant increase in lymphocytes counts; and viability 70 . Line et al, (1996) 71 reported that aggression is associated with the strong immune response which may be due to NE elevation 72 .…”

“…Line et al, (1996) 71 reported that aggression is associated with the strong immune response which may be due to NE elevation 72 . However, losers have shown weaker immune response demonstrated by the reduction in lymphocytes counts, and viability 70 . This may be due to higher corticosterone levels in losers with depressive behavior, which is immunosuppressant, thus induced cell destruction and lymphocytopenia 73; 74; 75 .…”

“…Autism may result from maternal or host autoantibodies that disrupt neurons that regulate social behavior 111 . Schizophrenia represents overactive immune response which results in neurotransmitters dysregulation 112 , 2020, 4 (3), 72-82 pathways in neurodegeneration occurred in epilepsy 113,96,70,114 . Niraula et al, 2017 115 have reviewed the impact of chronic stress on the aging of immune cells.…”

Antidepressant potential of diphenyl dimethyl bicarboxylate (DDB) in a modified forced swimming test

“…Furthermore, it decreased anxiety and increased exploratory tendency and curiosity [8]. It is reported that the monoaminergic hypothesis is the most accepted mechanism of depression by major depletion of brain 5HT, NE, and DA [4].Furthermore, the antioxidant and antiinflammatory impact of DDB which is extracted from Schisandra Chinensis protects against central neurodegeneration & neuroinflammation which have been reported in various CNS disorders[28][29][30][31][32]. So the antidepressant-like effect of DDB which was observed in the current study may be considered as a parallel to the observed changes in neurotransmitters and the increase in motor activity or to the decrease of anxiety as observed in the current study.…”