Korean J Physiol Pharmacol.  2013 Dec;17(6):485-491. 10.4196/kjpp.2013.17.6.485.

Effect of Neurosteroid Modulation on Global Ischaemia-Reperfusion-Induced Cerebral Injury in Mice

Affiliations
  • 1Rayat and Bahra Institute of Pharmacy, Sahauran, Mohali-140104, Punjab, India.
  • 2Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, Punjab, India. nirmal_puru@rediffmail.com

Abstract

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3alpha HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.

Keyword

Carbamazepine; Global-ischaemia-reperfusion injury; Indomethacin; Mexiletine; Neurosteroids

MeSH Terms

Animals
Carbamazepine
Carotid Arteries
Hand Strength
Indomethacin
Mexiletine
Mice*
Neuroprotective Agents
Neurotransmitter Agents
Reperfusion
Sodium Channels
Carbamazepine
Indomethacin
Mexiletine
Neuroprotective Agents
Neurotransmitter Agents
Sodium Channels

Figure

  • Fig. 1 (A) Effect of carbamazepine on ischemia reperfusion-induced cerebral infarct size and its modulation by mexiletine and indomethacin. CBZ, carbamazepine; Indo, indomethacin; Mexil, mexiletine. Values are expressed as mean (n=10)±S.E.M. a=p<0.05 vs sham; b=p<0.05 vs control; c=p<0.05 vs carbamazepine. (B) The representative photographs of TTC staining showing cerebral infarcted (yellow colour) and non-infarcted (red colour) areas. A, sham group; B, ischemia-reperfusion injury group; C, carbamazepine treated group; D, indomethacin+carbamazepine treated group.

  • Fig. 2 Effect of carbamazepine on ischemia reperfusion-induced changes in thiobarbituric acid reactive substances levels in the brain (TBARS) and its modulation by mexiletine and indomethacin. CBZ, carbamazepine; Indo, indomethacin; Mexil, mexiletine. Values are expressed as mean (n=10)±S.E.M. a=p<0.05 vs sham; b=p<0.05 vs control; c=p<0.05 vs carbamazepine.

  • Fig. 3 Effect of carbamazepine on ischemia reperfusion-induced impairment on motor performance and its modulation by mexiletine and indomethacin. CBZ, carbamazepine; Indo, indomethacin; Mexil, mexiletine. Values are expressed as mean (n=10)±S.E.M. a=p<0.05 vs sham; b=p<0.05 vs control; c=p<0.05 vs carbamazepine.

  • Fig. 4 Effect of various interventions on motor coordination. CBZ, carbamazepine; Indo, indomethacin; Mexil, mexiletine. Values are expressed as mean (n=10)±S.E.M. a=p<0.05 vs sham; b=p<0.05 vs control; c=p<0.05 vs carbamazepine.


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