Boosting Endogenous Resistance of Brain to Ischemia

Fen Sun, Stephen R. Johnson, Kunlin Jin, Victor V. Uteshev

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Most survivors of ischemic stroke remain physically disabled and require prolonged rehabilitation. However, some stroke victims achieve a full neurological recovery suggesting that the human brain can defend itself against ischemic injury, but the protective mechanisms are unknown. This study used selective pharmacological agents and a rat model of cerebral ischemic stroke to detect endogenous brain protective mechanisms that require activation of α7 nicotinic acetylcholine receptors (nAChRs). This endogenous protection was found to be (1) limited to less severe injuries; (2) significantly augmented by intranasal administration of a positive allosteric modulator of α7 nAChRs, significantly reducing brain injury and neurological deficits after more severe ischemic injuries; and (3) reduced by inhibition of calcium/calmodulin-dependent kinase-II. The physiological role of α7 nAChRs remains largely unknown. The therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential.

Original languageEnglish
Pages (from-to)2045-2059
Number of pages15
JournalMolecular Neurobiology
Volume54
Issue number3
DOIs
StatePublished - 1 Apr 2017

Keywords

  • Allosteric modulator
  • Choline
  • Neuroprotection
  • Nicotinic receptors
  • PNU-120596
  • PNU120596
  • Stroke

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