A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models

Abstract

The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.