Combined enriched environment÷atipamezole treatment transiently improves sensory functions in stroke rats independent from neurogenesis and angiogenesis.

Abstract

Functional recovery after cerebral ischemia may be enhanced by activation of the noradrenergic system and by environmental enrichment. The underlying mechanisms have remained elusive, but endogenous neurogenesis and perilesional angiogenesis have been speculated to contribute to the behavioral improvement. To address this question, neurogenesis in the subventricular zone (SVZ) and perilesional angiogenesis (RECA-1) were correlated with behavioral performance in forty Wistar rats subjected to transient middle cerebral artery occlusion (MCAO) or sham-operation. Atipamezole, an α2-adrenoreceptor antagonist (1 mg÷kg, i.p.), was administered for 10 days together with housing of rats in an enriched environment. MCAO rats and sham-operated rats housed in single non-enriched cages were used as controls. Histological analysis after 28-day behavioral follow-up showed a massive increase in doublecortin (DCX)-positive cells in the SVZ both in MCAO rats housed in single cages and in the enriched environment together with atipamezole treatment whereas perilesional RECA-1 staining for new blood vessels was not altered. Time to the first contact and time to remove sticky stimuli from the forelimbs indicated improved sensory processing, which disappeared after cessation of atipamezole administration. Skilled forelimb use as measured by performance in Montoya's staircase test was not affected by the treatment. There were no correlations between behavioral measures and histology. Thus, sensory facilitation or reversal of hypometabolism by the combined therapy may be the mechanism accounting for the improved behavior after stroke independent from neurogenesis and angiogenesis.