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Restoration of the Attenuated Neuroprotective Effect of Ischemic Postconditioning in Diabetic Mice by SGLT Inhibitor Phlorizin

[ Vol. 17 , Issue. 5 ]

Author(s):

Viny Mehta, Amit Kumar*, Amteshwar Singh Jaggi and Nirmal Singh*   Pages 706 - 718 ( 13 )

Abstract:


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 mice.

Conclusion: It may be concluded that the neuroprotective effect of iPoCo is abolished in diabetic mice, and SGLT plays an important role in neuroprotection.

Keywords:

Ischemia, diabetes, stroke, phlorizin, neuroprotection, iPoCo.

Affiliation:

CNS research lab., Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab, Chitkara College of Pharmacy, Chitkara University, Punjab, CNS research lab., Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab, CNS research lab., Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab

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