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Neuroprotective Potential of Transient Receptor Potential Melastatin‐2channel Inhibitor Flufenamic Acid in Experimental Model of Focal Cerebral Ischemia
Author(s) -
Medhi Bikash,
Harikrishnareddy Dibbanti
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb584
Subject(s) - neuroprotection , flufenamic acid , ischemia , medicine , pharmacology , riluzole , oxidative stress , transient receptor potential channel , excitotoxicity , glutamate receptor , brain ischemia , anesthesia , unfolded protein response , endocrinology , chemistry , apoptosis , receptor , biochemistry
Cerebral Ischemia remains third leading cause of death and disability worldwide. Although progress has been made in supportive care, efforts to guard the brain from ischemic neuronal death have failed. Recently transient receptor potential melastatin‐2 (TRPM‐2) ion channel have been identified as major culprit that initiates neuronal death in cerebral stroke. These channels raises the intracellular Ca 2+ levels and oxidative stress there by initiating mitochondrial membrane disruption, endoplasmic reticulum stress, glutamate excitotoxicity which initiates neuronal death. We therefore investigated the neuroprotective effect of TRPM‐2 channel inhibitor flufenamic acid (FA) for the treatment of Cerebral Ischemia. Materials and Methods Adult male Wistar rats weighing 250±20g were divided into six different groups viz sham operated group, vehicle treated group, four different doses of flufenamic acid (FA‐5mg/kg, FA‐10mg/kg, FA‐20mg/kg, and FA‐40mg/kg groups). Focal Cerebral Ischemia was induced by middle cerebral artery occlusion (MCAO) model. Neurobehavioral assessmentwere monitored by Longa et al., five point scale with 10 grading scores, infarct size was calculated by using of 2,3,5‐triphenyltetrazolium chloride (TTC) staining, oxidative stress parameters were estimated by biochemical parameters, and brain water content was measured by wet‐dry method. Results FA showed neuroprotection in a dose dependent manner. FA 20mg significantly diminished neurological deficits and reduced infarct size in rats. Further, an early calcium dependent rise in levels of MDA was also found to be significantly reduced in ischemic brain regions following FA treatment. With higher doses of FA brain edema was also significantly reduced. Conclusion The present study thus provide neuroprotective profile of FA in focal Cerebral Ischemia with its selective effect onTRPM‐2 channel. Support or Funding Information Post Graduate Institute of Medical Education and Research