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Brain Damage in Photo-induced Ischemia under Streptozotocin-Induced Diabetes in Mice with Pannexin 1 Protein Gene Knockout

  • M. A. Nikolaenko,
  • M. V. Gulyaev,
  • A. A. Volkova,
  • L. R. Gorbacheva

摘要

Abstract

Diabetes mellitus (DM), along with ischemia, is one of thetop ten causes of death in the global population, according to thelatest World Health Organization (WHO) data. Clinical research datahave revealed a high risk of stroke and heart attacks in patientswith diabetes. However, there is still a lack of understanding ofthe involvement of pannexin 1 (Panx1) protein in cerebral ischemiacombined with DM. In the presented study, we used the Panx1 geneknockout mice in models of streptozotocin-induced diabetes and photoinducedischemia to investigate the effect of the Panx1 on the severityof ischemic brain damage and systemic inflammation in mice witha combination of cerebral ischemia and diabetes. It has been foundthat under conditions of experimental diabetes, the knockout ofthe Panx1 gene significantly reduces the size of the ischemic lesion,stabilizes the ischemia-induced increase in the blood–brain barrierpermeability, reduces the number of errors in the sensorimotor testand the level of neutrophils in the blood. It is important to notethat the Panx1 knockout exhibits a protective effect only in thepresence of diabetes mellitus, without significantly affecting theseverity of ischemic brain injury in mice without streptozotocin-induceddiabetes. Panx1 knockout also did not affect the severity of hyperglycemiain animals in this diabetes model. It can be assumed that the efficacyof the treatment for pathologies combined with diabetes mellituscan be enhanced by incorporating pannexin channel blockers intothe complex therapy, representing a novel approach to addressingthese serious conditions.