NEUROPROTECTIVE EFFECTS OF VARIOUS DRUGS AGAINST NEURONAL DAMAGE

Abstract

The primary cause of cell damage in cerebral ischaemia is the reduction m CBF below the critical threshold needed for preservation of neuronal structures. The secondary cause is the triggering off of several destructive mechanisms (oedema; entry of Ca2+; release of EAAs; production of excess

free radicals and liberation of neurotransmitters). Thus, improvement of CBF or administration of drugs which can interfere with one or more of the previous mechanisms represent the possible approaches for therapeutic intervention.

Ischaemia may be broadly classified into 2 types, the focal and the global. The focal type results mainly from occlusion of a main artery such as the MCA, and thus affects the striatum (core of infarction) and cortex (periphery of infarction). • The collateral blood supply to the cortex allows for the supplied areas to be more readily salvaged by drugs.

Focal ischaemia was carried out in this study by occluding the MCA in both rats and mice. In rats, both the striatum and the frontal lobe of the cortex are affected, while in mice the damage is limited to the tempoparietal cortex. To test the potential neuroprotective effect of different agents, they were injected either before or after MCA-0 and the animals were killed 48 hrs after induction of ischaemia The brains were then removed and the infarct size was determined either by measuring the infarct volume (in rats) or the infarct area (in mice). The infarct area in mice was found to bear a direct correlation to the infarct volume .