Photothrombotic mouse models for the study of melatonin as a therapeutic tool after ischemic stroke

Melatonin is a potent neuroprotective agent which has shown therapeutic effects in animal models of brain injury such as stroke. Currently, there are few effective treatments for the therapeutics of stroke, the second leading cause of death and a major cause of disability worldwide. As demonstrated by the high number of publications during the last two decades, there is growing interest in understanding how and if melatonin could be a possible drug for stroke in humans, given also its very low and limited toxicity. Here, we describe the detailed protocol for performing the photothrombotic model of stroke which involves the occlusion of small cerebral vessels caused by the photoactivation of the previously injected light-sensitive dye Rose Bengal. Importantly, this model allows for the study of cellular and molecular mechanisms underlying the pathophysiology of stroke and thus can be used for investigating the neuropharmacological role of melatonin and the melatonin system in stroke. In particular, future research is warranted to demonstrate how and if melatonin impacts neurodegeneration, neuroprotection, and neuro-regeneration occurring after the brain injury caused by the occlusion of cerebral vessels.