Abstract TP102: Hyperexpression Of Adiponectin Improves Long-term Stroke Outcome In Young And Aged Mice

Abstract

Introduction: Previous studies showed that adiponectin (APN) has benefits on acute phase of ischemic brain injury. However, its role for neurobehavior recovery after stroke remains unclear, especially in aged rodents. In this study, we explored whether hyperexpression of APN could improve long-term recovery after stroke in both young and aged mice. Methods: Adeno-associated viral vector carrying APN gene (AAV-APN) was stereotactically injected in the striatum of adult (3 months) and aged CD-1 mice (20-22 months). One week after injection, transient middle cerebral artery occlusion (tMCAO) was performed. Expression of APN and its receptors in adult and aged stroke mice was assessed by Real-time PCR,western blot and immunohistochemistry. Cortical atrophy volume, Neurobehavior tests, angiogenesis and neurogenesis were also explored. Expression of phospho-AMPK and VEGF were investigated by western blot to further study the mechanism of APN. Results: In both adult and aged mice after stroke, immunohistochemistry and western blot analysis showed that expression of APN and its receptor AdipoR1 was increased. Comparing to the AAV-GFP and saline treated mice, cortical atrophy volume was attenuated, neurobehavior recovery was improved and angiogenesis was increased in the AAV-APN transduced mice (p<0.05). In addition, the expression of phospho-AMPK and VEGF was increased in the AAV-APN transduced adult and aged mice after cerebral ischemia (p<0.05). Moreover, phospho-AMPK inhibitor compound C treated AAV-APN-transduced mice developed larger atrophy volume (p<0.05), and the number of microvessels was significantly decreased compared to the control mice (p<0.05). P-AMPK,VEGF protein levels and VEGF mRNA level in the AAV-APN-transduced mice with compound C treatment were significantly reduced (p<0.05). Conclusions: Our results showed that overexpression of APN attenuates brain atrophy, improves neurobehavior recovery in both adult and aged mice, which is mediated by VEGF up regulation and the AMPK signaling pathway. Our findings suggest that APN may have great potential for ischemic stroke, even in aged animals.