TAT-PEP, a novel blocker of PirB, enhances the recovery of cognitive function in mice after transient global cerebral ischemia.
Neuronal damage and axonal regeneration inhibition are the main reasons to poor functional recovery after ischemia. Nogo-A signals inhibit axon outgrowth through the PirB receptor after ischemic reperfusion injury in central nervous system. We use TAT-PEP, a novel protein which could pass through the blood brain barrier, to block the function of PirB and identify the long-term neurological and behavioral recovery after bilateral common carotid artery occlusion (BCCAO) in mice. We observed that TAT-PEP promoted neuron survival and inhibited neuronal apoptosis. TAT-PEP increased the expression of Tau, GAP43 and MAP-2 proteins. In addition, the short-term and long-term cognitive functions were also enhanced, indicating that TAT-PEP had a long-term neuroprotective effect, which reduced neurologic injury and neuron loss, promoted neurite outgrowth and enhanced functional recovery after ischemia. These studies reveal the mechanism of PirB on stroke and offer a potential therapeutic method for cerebral ischemia in humans.
Department of Emergency, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
Liya
L
Li
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
Bin
B
Deng
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Shuang
S
Li
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Zhaoyu
Z
Liu
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Tao
T
Jiang
Department of Emergency, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China,. Electronic address: xiaozhaoy2012@163.com.
Zhaoyang
Z
Xiao
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: dr.wangqiang@139.com.
Qiang
Q
Wang
D000818:Animals; D004195:Disease Models, Animal; D015696:Gene Products, tat; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D000070798:Nogo Proteins / Q000378:metabolism*; D011971:Receptors, Immunologic; D020127:Recovery of Function / Q000187:drug effects*
D015696:Gene Products, tat; D000070798:Nogo Proteins; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic
Cognitive function recovery; Global cerebral ischemia; Neurite regeneration; Nogo-A; PirB