Combined swimming with melatonin protects against behavioural deficit in cerebral ischemia-reperfusion injury induced rats associated with modulation of Mst1- MAPK -ERK signalling pathway.

Background: The inconvenience of social and behavioural deficits after cerebral ischaemia reperfusion (I/R) injury is still not well documented.

Aim: We aimed to study the protective effect of preconditioning swimming exercise combined with melatonin against cerebral I/R induced injury.

Methodology: Sixty rats were allocated into 6 groups; groups I and II served as control. Groups 3,4,5,6 subjected to bilateral carotid ligation for 30 minutes (min.) followed by reperfusion. Group 3 left untreated while groups 4 and 6; underwent swimming exercise 30 min/day, five days a week for three weeks before the surgery. Groups 5 and 6 treated with melatonin 30 minutes before the operation, then, all rats in groups 4, 5,6 were subjected to I/R. After that, groups 5 and 6 treated with 2^nd dose of melatonin 30 minutes after reperfusion.

Results: Combined strategy exhibited the most neuroprotective effect through prevention of cerebral I/R induced inflammation, oxidative stress and apoptosis with subsequent improvement in socio behaviour deficits and enhanced Glial cell proliferative capacity.

Conclusion: The protective contribution of combined strategy is associated with modulation in Macrophage-stimulating 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (MST1/MAPK/ERK) pathway which may explain, at least in part, its protective potential.