Abstract
Therapeutics targeting the Nogo-A signal pathway hold promise to promote recovery following brain injury. Based on the temporal characteristics of Nogo-A expression in the process of cerebral ischemia and reperfusion, we tested a novel asynchronous treatment, in which TAT-M9 was used in the early stage to decrease neuronal loss, and TAT-NEP1-40 was used in the delayed stage to promote neurite outgrowth after bilateral common carotid artery occlusion (BCCAO) in mice. Both TAT-M9 and TAT-NEP1-40 were efficiently delivered into the brains of mice by intraperitoneal injection. TAT-M9 treatment promoted neuron survival and inhibited neuronal apoptosis. Asynchronous therapy with TAT-M9 and TAT-NEP1-40 increased the expression of Tau, GAP43 and MAP-2 proteins, and enhanced short-term and long-term cognitive functions. In conclusion, the asynchronous treatment had a long-term neuroprotective effect, which reduced neurologic injury and apoptosis, promoted neurite outgrowth and enhanced functional recovery after ischemia. It suggests that this asynchronous treatment could be a promising therapy for cerebral ischemia in humans.
Declaration of interest
This work was supported by the National Natural Science Foundation of China (Grant Nos. 81473488, 81228022, 81271342, 81471373), the Overseas, Hong Kong & Macao Scholars Collaborated Researching Fund (Grant 81228022), the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2012BAI20B02) and the Science and Technology Project of Fujian Province (Grant No. 2012Y0054, Guozhong Chen, Department of Anesthesiology, Fuzhou General Hospital).
The authors (Liya Lia, Bin Deng, Shiquan Wang, Haixing Zhong, Zhaoyu liu, Weilin Jin, Tao Jiang, Zhaoyang Xiao and Qiang Wang) declare that they have no conflict of interest.