TAT-PEP, a novel blocker of PirB, enhances the recovery of cognitive function in mice after transient global cerebral ischemia

Behav Brain Res. 2017 May 30:326:322-330. doi: 10.1016/j.bbr.2017.03.021. Epub 2017 Mar 16.

Abstract

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.

Keywords: Cognitive function recovery; Global cerebral ischemia; Neurite regeneration; Nogo-A; PirB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Products, tat*
  • Ischemic Attack, Transient / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / physiology*
  • Neurites / physiology*
  • Nogo Proteins / metabolism*
  • Receptors, Immunologic*
  • Recovery of Function / drug effects*

Substances

  • Gene Products, tat
  • Nogo Proteins
  • Pirb protein, mouse
  • Receptors, Immunologic