Research ReportGene expression associated with an enriched environment after transient focal ischemia
Research Highlights
►Motor function was improved in ischemic rats housed in the enriched environment. ►There were no significant differences in the size of the infarct area between the enriched environment and standard cages. ►Decreases in the gene expression of Egr-1, -2, and BDNF in the enriched environment in both sides of the cortices
Introduction
Stroke is the major worldwide cause of mortality and morbidity. Motor exercise is essential for functional recovery after stroke. Forced exercise, for example, treadmill running or constraint-induced movement therapy, has been shown to enhance the functional recovery of motor skills after experimental ischemic stroke (Kim et al., 2005, Kim et al., 2009, Taub et al., 2002); however, other studies demonstrated that treadmill running produced negative physiological adaptations induced by stress (Moraska et al., 2000) and a constraint-induced movement study did not improve functional outcome after brain ischemia (Muller et al., 2008). Therefore, the effect of forced exercise on functional recovery after stroke is controversial. On the other hand, an enriched environment, which induces social interactions, perceptive stimuli, and voluntary exercise, has recently been demonstrated to positively influence the outcome after experimental brain damage. Several studies demonstrated that animals housed in an enriched environment after ischemic stroke obtained a better functional outcome as compared with those housed in standard cage (Biernaskie and Corbett, 2001, Nygren and Wieloch, 2005, Ohlsson and Johansson, 1995). Gene expression under an enriched environment was examined in the hippocampus and sensorimotor cortex after experimental brain injury using microarray techniques (Keyvani et al., 2004, Ronnback et al., 2005). These studies indicated that an enriched environment affected the mRNA expression levels of microtubule-associated protein, synapse-related molecule, neurotransmitter receptors, neuroprotective factors, and so forth. However, one study could not confirm the gene changes identified from the microarray analysis using real-time PCR (Ronnback et al., 2005), and this study only evaluated the mRNA expression levels of the non-ischemic side. Another study demonstrated that an enriched environment induced similar changes of mRNA expression in normal and ischemic brains (Keyvani et al., 2004). However, these studies did not show functional recovery after brain injury and it remains unclear which factors affect gene expression more profoundly, the enriched environment or the ischemic brain injury itself. Limited evidence exists for gene expression associated with functional recovery after focal brain ischemia under an enriched environment. The purpose of the present study was to elucidate the expression of genes under an enriched environment after experimental stroke in the ischemic and non-ischemic sides of the cortices.
Section snippets
Infarct areas and recovery of the neurological functions
The infarct area evaluated by immunoreactivity to MAP-2 in the enriched group (51.9% ± 9.4%) was not significantly different to that in the standard group (53.8% ± 10.6%) (Fig. 1).
The neurological functions of the rats in both ischemic groups gradually improved after the first evaluation (Fig. 2). There were no significant differences in the NSS at 2 and 4 weeks after the first evaluation between the enriched and standard groups. For motor function evaluated by the inclined plane test in 2
Discussion
We examined gene expression associated with an enriched environment after transient focal ischemia. Motor function improved in ischemic rats housed in the enriched environment compared with those in standard cages; however, there were no significant differences in the size of the infarct area at 4 weeks after brain ischemia between the ischemic rats in the enriched environment and those in standard cages. These findings were consistent with previous studies (Biernaskie and Corbett, 2001, Nygren
Conclusion
Motor function was improved in rats housed in the enriched environment. Decreases in the gene expression of Egr-1, -2, and BDNF in the rats housed in the enriched environment in both sides of the cortices could indicate that alterations in gene expression are induced in the whole brain at 4 weeks after transient focal ischemia.
Animals and surgical procedures
All animal procedures were approved by our Institutional Animal Research Committee and were performed in accordance with the standards published by the National Research Council. Male Sprague–Dawley rats, 9 weeks old and weighing 270–320 g, were used in this study. Rats were anesthetized with chloral hydrate (400 mg/kg body weight i.p.), and transient focal brain ischemia was produced by the intraluminal occlusion of the ostium of the right middle cerebral artery (MCA) for 60 min with nylon
Acknowledgments
This study was supported in part by a grant from the Mitsubishi Pharma Research Foundation, by research grants for cardiovascular diseases (21A-4, 22-4-1) from the Ministry of Health, Labor, and Welfare of Japan, and by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science.
Disclosures
None.
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