Asynchronous therapy targeting Nogo-A enhances neurobehavioral recovery by reducing neuronal loss and promoting neurite outgrowth after cerebral ischemia in mice. (2nd January 2016)

• Record Type: Journal Article
• Authors: Li, Liya; Deng, Bin; Wang, Shiquan; Zhong, Haixing; Liu, Zhaoyu; Jin, Weilin; Jiang, Tao; Xiao, Zhaoyang; Wang, Qiang
• Is Part Of: Journal of drug targeting. Volume 24:Number 1(2016)
• Page Start: 13
• Page End: 23
• Publication Date: 2016-01-02
• Subjects: Global cerebral ischemia -- neurite regeneration -- neurological function recovery -- Nogo-66 receptor -- Nogo-A; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.3109/1061186X.2015.1052070
• Languages: English
• ISSNs: 1061-186X

Abstract

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.