Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

Abstract

Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.

Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model

“…We created a C57/BL6 male mouse SE model, as previously described 30 . Seven-week-old mice received 2 mg/kg of scopolamine methyl bromide (intraperitoneally [i.p.…”

Temporal lobe epilepsy with hippocampus sclerosis: prevalence, etiology, and treatment options with herbal medicines

“…29,30 Animal models give us a chance to understand the pathophysiology of epilepsy. 31,32 Choosing a correct animal model is critical and important because age, strain, weight, and gender play vital roles in the development of a model of epilepsy. Precise and carefully controlled variables may facilitate to obtain a reliable animal model of TLE-HS with reduced mortality and variability in behaviors.…”

“…Lithium is widely used as a mood stabilizer in depression and frequently used for the treatment of chronic neurodegenerative diseases. 32,33,35,39 Recently, it is reported that lithium-pilocarpine model does not just reduce the mortality but also reduced status epilepticus induction and morbidity. 30,31,33,37 Furthermore, to reduce the severe effects of pilocarpine, methylscopolamin-bromide can be injected 30 minutes prior to pilocarpine.…”

What is the Role of Lithium in Epilepsy?

“…Studies have reported neuroprotective action of low dose Li in cellular and animal models of epilepsy, AD, Down syndrome, Huntington’s disease, PD, stroke, ALS, spinal cord injury, spinal muscular atrophy, neurodevelopmental disorders, and retinal degeneration [ 18 , 92 , 93 ]. Lithium treatment at therapeutic concentrations (0.6-1.25 mEq/L) showed either a reduction in seizures in the majority of the epileptic patients or a lack of effect in a few patients and rarely increased seizure activity [ 89 , 94 – 97 ]. Li is also reported to increase seizure threshold in acute rodent models of seizures such as Maximal Electroshock (MES) and Pentylenetetrazol (PTZ), as well as in chronic models such as PTZ kindling and Li-Pi (post-treatment) [ 93 , 98 ].…”