Sequential patterns of inhibin subunit gene expression following hypoxic-ischemic injury in the rat brain

Injury to the central nervous system initiates a series of signals that control cell survival and rearrangement, leading to some functional recovery. Using a unilateral model of hypoxic-ischemic brain injury, we report strong induction of inhibin beta A and alpha subunit messenger RNA in several regions of the brain and provide evidence for novel roles for the inhibin/activin family of peptides in modulating neural function. Expression was visualized by in situ hybridization and the beta A subunit was observed as early as 1 h after injury in the dentate gyrus of the non-ligated hemisphere. Strong induction was seen in the hippocampus, piriform cortex and amygdala on the non-ligated hemisphere 24 h after injury. The early induction of inhibin beta A was associated with seizure activity, since administration of the anticonvulsant carbamazepine (8 mg/kg) markedly attenuated the signal. Only background expression was observed for the alpha and beta B subunits at these early time points. A bilateral induction of both beta A and alpha subunit messenger RNA was demonstrated in the meningeal membrane from three to seven days after injury. This second wave was not blocked by carbamazepine. Thirdly, beta A and alpha subunit expression was observed in the infarct from days 5 to 7. However, expression was not co-localized with isolectin B4 staining for reactive microglia or astrocytes, but instead the pattern of distribution strongly suggested that inhibin/activin was induced around microvessels. These data demonstrated three distinct waves of beta A subunit expression following hypoxic-ischemic injury, two of which coincided with alpha subunit expression. The early induction of beta A subunit was seizure related, whereas subsequent co-induction of beta A and alpha subunit suggested involvement in vascular and meningeal reactions. These results suggest specific roles for both activin and inhibin in the central nervous system during recovery from injury.