Neuropharmacology

Biography

Biography: Abdul Khayum K

Abstract

The present study has been designed on the hypothesis that administration of low dose of glutamate in cerebral ischemia might attenuate the excitotoxicity in neurons through its pre-synaptic auto-receptor regulatory mechanism, rather than the intensification of neurodegenerative conditions. To test the hypothesis, the effect of L-Glutamic acid 400μM/kg (L-GA) was evaluated in bilateral common carotid artery occlusion (BCCAo) induced global ischemic mice model. Global ischemia in mice was induced by occlusion of both the common carotid artery (BCCAo) for 20 min followed by reperfusion injury. L-GA was infused slowly through the tail vein, 30 min before the surgery, and every 24 hrs thereafter, until the experiment was completed. The time dependent change in the cerebral blood flow (CBF) was monitored using Laser Doppler image analyzer. The neurotransmitters and neurobiochemicals were measured in the different regions of brain at 0, 24, 48, and 72 hrs respectively after reperfusion injury. The results have shown that administration of L-GA increased the locomotor activity, muscle co-ordination, and CBF in ischemic mice at 72 hrs after ischemic insult in comparison to 24 and 48 hrs. L-GA administered group exhibited significant reduction in the glutamate level in cortex, striatum, and hippocampus regions at 72 hrs whereas gamma aminobutyric acid (GABA) levels were elevated in all three brain regions studied. Further, it elevated the glutathione (GSH) level and attenuated the nitric oxide (NO) content, but failed to restore the adenosine tri-phosphate (ATP) level after 72 hrs of IR. Memantine (MN) has been used as the standard drug. The study concludes that the gradual reduction of glutamate along with elevation of GABA in different brain regions may have contributed the neuroprotective effect of L-GA. Hence slow infusion of ultra low dose of L-GA could be beneficial in controlling excitotoxicity neurodegeneration in ischemia conditions.