All India institute of Medical Sciences
Pharmacology

Presenter of 1 Presentation

SAFINAMIDE AMELIORATES CEREBRAL ISCHEMIA-REPERFUSION INJURY IN RATS BY ATTENUATING OXIDATIVE STRESS, INFLAMMATION AND APOPTOSIS

Session Type
Oral Presentations
Date
27.10.2021, Wednesday
Session Time
09:50 - 10:30
Room
ORAL PRESENTATIONS 1
Lecture Time
10:10 - 10:20

Abstract

Background and Aims

With spectacular failure in searching an adjunctive neuroprotective agent for ischemic stroke, exploring and repurposing an already approved drug has become a lower risk alternative. Safinamide, a recently approved drug for Parkinson’s disease, has shown neuroprotective effects in various diseases. The present study investigated the effect of safinamide in experimental model of ischemic stroke in rats.

Methods

Middle cerebral artery occlusion (MCAo) was performed in Sprague Dawley rats. Dose-selection (20, 40 and 80 mg/kg), therapeutic-time-window (ischemia/reperfusion I/R, post-reperfusion 0h/2h and post-reperfusion 2h/4h) and sub-acute (3-days) studies were performed. Effective dose and time-point were selected based on neurobehavioral parameters and infarct size reduction assessed 24h post-reperfusion. Study was extended for 72h. Effects on neurobehavioral parameters and infarct size reduction (MRI) were assessed. To explore the basis of neuroprotection, oxidative stress (MDA, GSH, SOD, NOX-2), inflammatory cytokines (TNF-α, IL-1β, IL-10) and apoptosis (Bax, Bcl-2, cleaved-caspase-3 expression and TUNEL staining) were studied.

Results

Safinamide (80 mg/kg) given post-ischemia and -reperfusion (Saf I/R) and post-reperfusion (Saf 0h/2h) showed significant reduction in infarct size and improvement in neurobehavioral parameters. Safinamide (80 mg/kg) was administered post-reperfusion for 3-days. Significant improvement in motor-coordination and infarct size reduction (TTC staining and MRI) was observed. Additionally, safinamide treatment significantly improved altered redox homeostasis and inflammatory cytokine levels. The deranged expression of apoptotic markers and increased TUNEL positive cells in cortex after MCAo were significantly normalized with safinamide treatment.

Conclusions

The results demonstrated neuroprotective potential of safinamide in cerebral I/R injury and can be considered for repurposing in ischemic stroke.

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