Summary: | Ph.D., Faculty of Science, University of the Witwatersrand, 2011 === This study investigated the effect of exogenous melatonin administration on
transient global cerebral ischemia and adult neurogenesis in adult male Sprague-
Dawley rats. It also determined serum melatonin concentrations in all the
experimental groups and established any effect of melatonin on estimated total
granule cell numbers. Adult male Sprague-Dawley rats were divided into eight
groups with each group consisting of 6 rats (n = 6). Post-induction time durations
of 72 hours and 7 days was used. Single dose of 5 mg/kg exogenous melatonin
was administered at each phases of 30 minutes before and after a 10 minutes
transient bilateral occlusion of the common carotid arteries in the different groups,
followed by reperfusion. Rats were anesthetized with 20 mg/kg of ketamine and
2.5 mls of blood was collected via cardiac puncture for estimation of serum
melatonin concentration using commercially prepared radioimmunoassay ELISA
kit. Free floating brain sections cut at 50 μm were immunostained for Ki-67,
marker for proliferating cells. The total granule cell number in the dentate gyrus
was estimated using the optical fractionator method on plastic embedded brain
sections. Mean melatonin concentration (pg/mol) was 268.54 ± 28.73 (72 hours)
and 277.83 ± 28.73 (7 days) compared to the sham control; 266.94 ± 37.6 and non
surgical 262.96 ± 23.85 respectively. Differences in the concentration were not
statistically significant (P<0.05). Histological finding indicated neuropil
disruption with potentiation of restoration as the post ischemia days progressed in
the melatonin administered groups. The estimated total granule cell number in the
dentate gyrus of the hippocampus was not affected by exogenous melatonin
administration. However, there was potentiation in proliferations of the
neurogenic niche in the dentate gyrus of the hippocampus demonstrating a very
strong indications that melatonin enhanced the generations of proliferating cells in
adult male Sprague-Dawley rats.
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