Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats

• Investigate functional outcomes, infarct size and NOS after MCAO of rats.
• EE prior to MCAO decreased NOS and improved functional outcomes without affecting infarct size.
• Prior exposure to enriched environment improves the brain ischemic tolerance.

Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury is neuroprotective in animal models. However, little is known about of the neuroprotective effects of EE exposure prior to injury. The current study examined the effects of prior EE exposure on inducible and neuronal nitric oxide syntheses (iNOS and nNOS) after transient middle cerebral artery occlusion (tMCAO) in rats. A total of 72 rats were exposed to EE or standard housing condition (SC) for 1 month, followed by 90-min MCAO and reperfusion or sham surgery, leading to the following three groups: (1) EE + MCAO (n = 24), (2) SC + MCAO (n = 24), (3) SC + sham (n = 24). Rats were sacrificed at 1, 6, or 24 h after MCAO (n = 6/group) for iNOS and nNOS mRNA quantification by real-time PCR and at 24 h after MCAO (n = 6/group) for iNOS and nNOS protein quantification by Western blot or were evaluated for neurological function outcomes, then sacrificed to assess infarct volume (n = 6/group). Results showed that prior exposure to EE reduced iNOS and nNOS mRNA and protein and improved neurological status after MCAO without affecting infarct volume, suggesting that EE may provide neuroprotection via ischemic preconditioning.