Long-term effects of environmental stimulation following hypoxia-ischemia on the oxidative state and BDNF levels in rat hippocampus and frontal cortex.

Environmental enrichment recovers memory deficits without affecting atrophy of the hippocampus adult rats submitted to neonatal hypoxia-ischemia (HI). The present study was designed to investigate whether the modulation of brain oxidative status and/or BDNF content, as assessed in adulthood, are involved with the functional neuroprotection caused by environmental enrichment in animals receiving neonatal HI. Male Wistar rats, in the 7th postnatal day, were submitted to the Levine-Rice model of neonatal hypoxia-ischemia, comprising permanent occlusion of the right common carotid artery and a 90 min period of hypoxia (8% O(2)-92% N(2)). Starting 2 weeks after the HI event, animals were stimulated by the enriched environment (1 h/day for 9 weeks). Rats were sacrificed approximately 24 h after the end of enrichment period and some oxidative stress parameters, specifically the free radical levels, macromolecules damage and superoxide dismutase activity, in hippocampus and frontal cortex samples were determined. BDNF levels were also measured in the same encephalic structures. Indexes of macromolecules damage, TBARS levels and total cellular thiols, as well as free radical levels were unchanged in both studied structures. An increased SOD activity in the right hippocampus of HI group maintained in standard environment was found, this effect was reversed in HI enriched group. Moreover, BDNF levels were increased only in the hippocampus of non-stimulated HI group. These results suggest that the environmental enrichment protocol bearing cognitive protection is not associated to increases in BDNF expression nor SOD activity in hippocampus of the rats, as assessed in adulthood, submitted to neonatal hypoxia-ischemia.

Early enriched housing results in partial recovery of memory deficits in female, but not in male, rats after neonatal hypoxia-ischemia.

Our previous results indicated that stimulation by daily environmental enrichment (EE) recovered memory deficits without affecting hippocampus damage in adult male rats submitted to neonatal hypoxia-ischemia (HI). The present study investigated whether early continuous housing in an enriched environment would be effective in preventing spatial and recognition memory both in adolescent and adult female and male rats, as well as the possible benefits of continuous EE in alleviating hippocampal and striatal atrophy consequent to the neonatal HI. Wistar rats in the 7th PND were submitted to the HI and, in the day after, were housed in an enriched environment (8th-30th PND). Subsequently, performance of animals in the novel-object recognition and in two water maze tasks was assessed; in adulthood, animals' behavior was reassessed in the water maze. Rats were sacrificed and both hippocampal volume and striatal area were estimated following the completion of behavioral study. Post-HI cognitive deficits in the object recognition test were completely recovered by the EE. However, memory impairment in the water maze was only partially prevented by EE; this effect was observed especially in female rats on the working memory protocol. As for the morphological assessment, there was no enrichment effect over the loss of hippocampus volume and striatum area. In conclusion, present data indicate that early housing in EE caused performance recovery in object recognition and a partial improvement in the working memory spatial task in adolescent females after neonatal HI; however no effects of enrichment were revealed in adult animal's performance or in the extension of tissue atrophy of hippocampus and striatum consequent to HI.