Environmental influence on brain-derived neurotrophic factor messenger RNA expression after middle cerebral artery...

Enriched environment significantly enhances postischemic functional outcome. We have tested the hypothesis that housing in enriched environment stimulates gene expression for brain-derived neurotrophic factor. After ligation of the middle cerebral artery in male spontaneously hypertensive rats, they were housed in individual cages for 30h, then housed either in standard cages or in an enriched environment. The rats were killed two to 30days after the ischemic event. Cryostat coronal sections through the dorsal hippocampus (Bregma -3.3) were processed for in situ hybridization using a rat-brain-derived neurotrophic factor messenger RNA antisense oligonucleotide probe. Postischemic gene expression was significantly higher in standard rats than in enriched rats in contralateral and peri-infarct cortex and in most parts of the hippocampus two, three and 12days after the ischemic event, with a trend for higher-than-baseline levels in standard rats and lower-than-baseline levels in enriched rats. At 20 and 30days the values for both groups were below baseline levels. Contrary to our hypothesis, gene expression in rats postoperatively housed in enriched environment was significantly lower than in standard rats at a time when other studies have reported hyperexcitability in the ipsilateral and contralateral cortex. Should the low messenger RNA levels correspond to low protein synthesis, this might indicate that dampening of the early postischemic hyperexcitability may be beneficial. Low levels in both groups at 20 and 30days may correspond to loss of callosal connections in the opposite hemisphere and to horizontal cortical connections in the lesioned hemisphere.