Uncontrolled diabetes worsens cerebral ischemia-reperfusion injury in rats: insights into the involved mechanisms
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Uncontrolled diabetes; Global cerebral ischemia; Oxidative Stress


Uncontrolled diabetes mellitus (DM) has been associated with poor clinical outcomes in patients with ischemic stroke. Limited knowledge is available regarding the molecular mechanisms and the etiological complexity of both pathologies. Hence, this study aimed to investigate the interplay between long-term DM and ischemic stroke. A comparative study was held between long-term DM-induced adult male Wistar rats which were subjected to sham operation or global cerebral ischemia/reperfusion (I/R) injury on one hand, and adult male Wistar rats which were subjected to sham operation or global cerebral I/R injury on the other hand.
Results showed a disturbance in cerebral oxidative stress parameters (catalase, reduced glutathione and malondialdehyde) in diabetic rats compared to non-diabetic ones. Additionally, in comparison with sham diabetic group, diabetic I/R-injured rats showed up regulation of cerebral oxidative stress, caspase-3 and tumor necrosis factor- alpha (TNF-α) protein expression along with increase in carotid inducible nitric oxide synthase (iNOS) protein expression and downregulation of carotid endothelial nitric oxide synthase (eNOS) protein expression. However, no significant difference was observed in term of cerebral oxidative stress, cerebral caspase-3 and TNF-α protein expression upon comparing non-diabetic I/R-injured rats and diabetic rats subjected to cerebral I/R injury. Carotid vascular dysfunction is prominent in diabetic I/R-injured rats compared to non-diabetic rats with cerebral I/R injury. 
This study supposed that long term diabetes could exacerbate brain damage following global cerebral I/R injury via promoting inflammation, oxidative stress and vascular dysfunction. Diabetes-mediated vascular dysfunction in ischemic stroke warrants further experimental and clinical investigations to be fully elucidated.

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