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Journal of Neurology and Neurorehabilitation Research | Volume 3

August 23-24, 2018 | Paris, France

Neurology and Neurological Disorders

International Conference on

Effect of dimethyl fumarate on Apoptosis and Neuroinflammation in PTZ kindling model in rats

Neha Singh

Postgraduate Institute of Medical Education and Research, India

oles of apoptosis and neuroinflammation have been

well established in the pathogenesis of epilepsy. It has

been reported that the activation of nuclear factor-erythroid

2-related factor-2 (Nrf2) contributes to the attenuation of

inflammation by inhibiting nuclear factor-kB (NF-kB) pathway.

Current study was designed to evaluate anti-apoptotic, anti-

inflammatory and anti-oxidative roles of dimethyl fumarate

(DMF), an activator of Nrf2, in chemical kindling model in

rats. Chemical kindling model was established in Wistar rats

by intraperitoneal (i.p.) administration of pentylenetetrazole

(PTZ). Animals were treated with DMF (60 mg/kg) to activate

the Nrf2 antioxidant response element (ARE) pathway. The

animals were assessed for seizure score, neuronal damage

and inflammatory cytokines levels (IL-1β, IL-6 and TNF-α) in

hippocampus. The mRNA levels of various genes (Nrf2, HO-1,

NQO1, Bcl2, Bax, Caspase 3, NF-kB, IL-6, IL-1β and TNF-α) were

quantified by real-time PCR. The expression of anti-oxidative

(Nrf2), apoptotic (Bax, Bcl2) and inflammatory (NF-kB) proteins

were analysed by western blot. Immunohistochemistry (Bax)

and electron microscopy were done to assess apoptosis. There

was reduction in the seizure score, percentage of kindled rats

and neurological damage score in DMF treated rats. The levels

of pro-inflammatory cytokines were also decreased by DMF

treatment. DMF downregulated the expressionof inflammatory

(NF-kB) and apoptotic (Bax, Caspase-3) genes and proteins.

DMF treatment increased the gene expression of Nrf2, HO-

1, NQO1, Bcl-2 and protein expression of Nrf2 and Bcl2. The

present study demonstrated anti-apoptotic, anti-inflammatory

and anti-oxidative effect of DMF in PTZ kindled rats. Therefore,

it could be a potential new avenue to target the pathological

changes during epileptogenesis.