Neuroglobin protects against cerebral ischemia/reperfusion injury in rats by suppressing mitochondrial dysfunction and endoplasmic reticulum stress-mediated neuronal apoptosis through synaptotagmin-1.

Cerebral ischemia/reperfusion (I/R) injury remains a grievous health threat, and herein effective therapy is urgently needed. This study explored the protection of neuroglobin (Ngb) in rats with cerebral I/R injury. The focal cerebral I/R rat models were established by middle cerebral artery occlusion (MCAO) and neuronal injury models were established by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. The brain injury of rats was assessed. Levels of Ngb, Bcl-2, Bax, endoplasmic reticulum stress (ERS)-related markers, and Syt1 were measured by immunofluorescence staining and Western blotting. The cytotoxicity in neurons was assessed by lactate dehydrogenase (LDH) release assay. Levels of intracellular Ca2+ and mitochondrial function-related indicators were determined. The binding between Ngb and Syt1 was detected by co-immunoprecipitation. Ngb was upregulated in cerebral I/R rats and its overexpression alleviated brain injury. In OGD/R-induced neurons, Ngb overexpression decreased LDH level and neuronal apoptosis, decreased Ca2+ content, and mitigated mitochondrial dysfunction and ERS-related apoptosis. However, Ngb silencing imposed the opposite effects. Importantly, Ngb could bind to Syt1. Syt1 knockdown partially counteracted the alleviation of Ngb on OGD/R-induced injury in neurons and cerebral I/R injury in rats. Briefly, Ngb extenuated cerebral I/R injury by repressing mitochondrial dysfunction and endoplasmic reticulum stress-mediated neuronal apoptosis through Syt1.