Aim: The study has been commenced to discover the potential of sodium dependent glucose
co-transporters (SGLT) in neuroprotective mechanism of ischemic postconditioning (iPoCo)
in diabetic and non-diabetic mice.
Methods: Cerebral ischemic injury in mice was induced by bilateral carotid artery occlusion (BCAO)
for 12 min followed by reperfusion for 24 hr. For iPoCo, three episodes of carotid artery
reperfusion and occlusion of 10 sec each were instituted immediately after BCAO, followed by 24
hr reperfusion. Learning and memory were evaluated using the Morris water maze test. Motor coordination
was assessed using rotarod test, inclined beam walking test, neurological severity score
(NSS), and lateral push response. Glutathione and Thiobarbituric acid reactive species level was
quantified to evaluate the oxidative stress; the cholinergic activity of the brain was estimated in
terms of acetylcholinestrase activity, and the levels of myeloperoxidase were measured as inflammation
marker. Cerebral infarct size was evaluated using triphenyltetrazolium chloride staining.
Fasting blood glucose levels of animals were taken before and 6 hr after the surgical procedure.
Results: BCAO resulted in impairment of memory and motor coordination and biochemical alterations
along with a marked rise in cerebral infarct size and NSS. iPoCo diminished the deadly effect
of BCAO in non-diabetic mice; however, it failed to abolish the deleterious effects of ischemia-
reperfusion injury in diabetic mice. Pretreatment of Phlorizin (SGLT-inhibitor) potentiated the
neuroprotective effects of iPoCo in non-diabetics and restored the protective effect of iPoCo in diabetic
Conclusion: It may be concluded that the neuroprotective effect of iPoCo is abolished in diabetic
mice, and SGLT plays an important role in neuroprotection.