#129 Targeting central cannabinoid receptors for exploring their potential ischemic preconditioning like

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Jain, P. .; Kaushik, A. .; Aggarwal, H. .; Luhach, K. . #129 Targeting Central Cannabinoid Receptors for Exploring Their Potential Ischemic Preconditioning Like. J Pharm Chem 2022, 8.

Abstract

Ischemic stroke is a chronic debilitating condition having co-morbidities running in parallel. Stroke can be referred to as a state of hypoperfusion of any organ, brain, and heart suffer the most as they are most sensitive to ischemic and hypoxic insults. Extensive research has shown that transient, sublethal ischemic episodes condition these cells and prevent them from the severe episodes of ischemia. But the limitation of this method is the unpredictability of stroke occurrence. Moreover, there are not many palliative approaches for the management of stroke. The need for better therapeutic outcomes to reduce the severity of the disease results in the development of new pharmacologically efficacious models like ischemic pre-conditioning and Ischemic post-conditioning. Ischemic preconditioning benefits arise in response to brief episodes of ischemia followed by a prolonged state of ischemia and subsequent restoration of the blood supply. IPC makes the cerebrum more resistant to upcoming ischemic insults. Ischemic post-conditioning is a technique in which repetitive periods of occlusion of vessels at the onset of reperfusion diminish reperfusion injury, proceeding to prolonged ischemic effects. We have identified that the pathways up and down-regulated during IPC coincide with the cerebral pathways modulated by cannabinoid receptors. CB receptors are found predominantly in the cortex, which plays a crucial role in learning, cognition, and locomotor movements. Based on our hypothesis, we have designed these studies to explore the potential of cannabinoid receptors in cerebral ischemic preconditioning responses in mice and to induce transient sub-lethal Ischemic preconditioning episodes. They evaluate the ischemic preconditioning benefits of cannabinoid receptor modulation using a battery of behavioral and biochemical methods. The methods that will be covered in this study include: Morris water maze test, Rota-rod test, Lateral push test, Inclined beam test, and Neurologic severity scores-estimating biochemical methods like TBARS, GSH, CAT, AChE, SOD, TTC staining, etc. Therefore, we can conclude that ischemic preconditioning and postconditioning exert a neuroprotective effect and are somehow associated with reducing infarct size.

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