Voglibose and saxagliptin ameliorate the post-surgical stress and cognitive dysfunction in chronic anaesthesia exposed diabetic MCAo induced ischemic rats

Chronic surgical anaesthesia and uncontrolled hyperglycemia are bidirectional risk factors for the development of psychiatric, cerebrovascular, and cardiovascular diseases.

The current study was designed to elucidate the neuroprotective effects of anti-diabetic agents in pre and post-surgical anaesthesia exposure on diabetic ischemic rats.

The diabetes type-2 was induced and rats having more than 250 gm/dl blood glucose levels were considered for study. Administration of anaesthetic agents (ketamine 100 mg/kg IP, xylazine 10 mg/kg IP) were done pre and post MCAo surgery for 7 days. The treatment with anti-diabetic agents (voglibose, saxagliptin, repaglinide, dapagliflozin) was carried out after 7 days of Post MCAo surgery for one week. After treatment, assessment of neurobehavioral function was carried out using Morris Water Maze. After that, brains were excised and bloods were collected from all groups subjected for assessment of neuromodulator levels, oxidative stress parameters, serum biochemical biomarkers.

The treatment with voglibose and saxagliptin not only improved neuromodulator levels statistically significant (p < 0.001) and cognitive profile but also significantly improved (p < 0.01) overall stroke serum biomarkers (Serum Glucose, GGT, CRP, CK-MB, LDH).

The results of the present study, suggested that chronic exposure of anaesthesia worsens the cognition and increases risk of stroke biomarkers in diabetic conditions. We can conclude that voglibose, saxagliptin, and dapagliflozin can significantly improve the postoperative mortality, morbidity, and cognitive dysfunction caused by post-surgical stress and chronic anaesthesia-induced cognitive dysfunction.