Overexpression of adiponectin improves neurobehavioral outcomes after focal cerebral ischemia in aged mice.

ABSTRACT

AIMS: To study whether adiponectin (APN) could improve neurological outcomes in aged mice after ischemic stroke. METHODS: Adeno-associated virus carrying APN gene was injected into aged and young adult mice 7 days before transient middle cerebral artery occlusion (tMCAO). Atrophic volumes and neurobehavioral deficiencies were determined up to 28 days after tMCAO. Focal angiogenesis was determined based on blood vessel number in the ischemic regions. RESULTS: Increased atrophic volume and more sever neurobehavioral deficits were found in the aged mice compared with young adult mice (P < 0.05). AAV-APN gene transfer attenuated atrophic volume and improved neurobehavioral outcomes, along with increased focal angiogenesis in both aged and young adult mice, compared with control animals (P < 0.05). In addition, the attenuation of atrophic volume and the improvement in neurobehavioral outcomes were much more significant in aged mice than in young adult mice after AAV-APN administration (P < 0.05). The number of microvessels in aged AAV-APN mouse ischemic brain was higher than in young adult AAV-APN treated mouse brain (P < 0.05). CONCLUSIONS: Our results demonstrate that APN overexpression reduces ischemic brain injury and improves neurobehavioral function recovery in aged mice than in young mice, suggesting APN is more beneficial in aged animals after ischemic stroke.