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

Diabetes mellitus (DM), along with ischemia, is one of the top ten causes of death in the global population, according to the latest World Health Organization (WHO) data. Clinical research data have revealed a high risk of stroke and heart attacks in patients with diabetes. However, there is still a lack of understanding of the involvement of pannexin 1 (Panx1) protein in cerebral ischemia combined with DM. In the presented study, we used the Panx1 gene knockout mice in models of streptozotocin-induced diabetes and photoinduced ischemia to investigate the effect of the Panx1 on the severity of ischemic brain damage and systemic inflammation in mice with a combination of cerebral ischemia and diabetes. It has been found that under conditions of experimental diabetes, the knockout of the Panx1 gene significantly reduces the size of the ischemic lesion, stabilizes the ischemia-induced increase in the blood–brain barrier permeability, reduces the number of errors in the sensorimotor test and the level of neutrophils in the blood. It is important to note that the Panx1 knockout exhibits a protective effect only in the presence of diabetes mellitus, without significantly affecting the severity of ischemic brain injury in mice without streptozotocin-induced diabetes. Panx1 knockout also did not affect the severity of hyperglycemia in animals in this diabetes model. It can be assumed that the efficacy of the treatment for pathologies combined with diabetes mellitus can be enhanced by incorporating pannexin channel blockers into the complex therapy, representing a novel approach to addressing these serious conditions.