MAO-B, GABRA5 identified as astrocyte targets in subcortical stroke

INDICATION: Stroke

Inhibiting MAO-B or GABRA5 could treat subcortical stroke by restoring regional glucose metabolism and alleviating diaschisis, neurological dormancy at sites distant from a focal brain injury. In a rat model of subcortical stroke, an MAO-B inhibitor tool compound or an shRNA targeting MAO-B in astrocytes restored glucose metabolism and decreased cortical diaschisis volume. Astrocyte-specific MAO-B knockdown reduced GABA production by reactive astrocytes, and a GABRA5 inverse agonist tool compound also restored glucose metabolism, suggesting that the effects of MAO-B inhibition were mediated by reductions in GABA production. In the model, the MAO-B inhibitor plus daily 20-minute rehabilitation training reduced deficits in fine and general motor function of the forelimb affected by the lesion...