Mixed efficacy of
neuroprotective drugs in clinical trials has led to the emergence of the approach of combination
therapy in
stroke. The present study was carried out to investigate the effect of the combination of
melatonin (potent
antioxidant) and
meloxicam (preferential inhibitor of
cyclooxygenase-2 enzyme) against a
middle cerebral artery occlusion model of
stroke in rats. Male Wistar rats in the weight range of 250-300 g were used. Rats were anesthetized using
chloral hydrate (400 mg/kg i.p) and subjected to 2 h of transient
middle cerebral artery occlusion.
Melatonin was administered at a dose of 20 mg/kg i.p. four times: at the time of
middle cerebral artery occlusion, 1.5 h after
middle cerebral artery occlusion, at the time of reperfusion, and 1 h after reperfusion.
Meloxicam (2.5 mg/kg) was administered 4 h after
middle cerebral artery occlusion. Motor performance tests (grip test, foot fault test, rotarod performance test, spontaneous locomotor activity), markers of oxidative stress, and
triphenyltetrazolium chloride staining were carried out 24 h after
middle cerebral artery occlusion. A vehicle-treated group was run in parallel. It was observed that
melatonin treatment improved the motor performance and significantly attenuated the levels of
malondialdehyde (MDA) as compared with the middle cerebral artery occluded group.
Meloxicam treatment at the dose used neither showed significant improvement on the motor performance nor decreased the levels of MDA significantly as compared with the middle cerebral artery occluded group. However, when the combination of the two drugs was used, better protection was observed as was evident by the significant decrease in the percent foot fault errors, the increase in the time spent on the rotarod, and the increase in the six-point neurological score and grip test score. There was also a significant decrease in the levels of MDA in the combination group. The results of the present study demonstrate that enhanced protection is observed with the use of a combination of
melatonin plus
meloxicam in the
middle cerebral artery occlusion model of
acute ischemic stroke in rats.