To explore the therapeutic effects of melatonin by two different routes, by caudal vein and intraperitoneal injection, on cerebral ischemia-reperfusion (IR) injury in adult rats.

60 Sprague-Dawley rats were randomly divided into normal control (CON), middle cerebral artery occlusion (MCAO), intraperitoneal and caudal vein injection groups. Nissl and immunohistochemical staining were used to observe the morphological and quantitative changes of neurons and the expression of cleaved Caspase-3, Fas and FasL proteins in the injured cerebral cortex.

More Nissl-stained and NeuN⁺ cells were observed in both the intraperitoneal and caudal vein injection groups as compared with the MCAO group (P < 0.05), and the number of Nissl-stained and NeuN⁺ cells in caudal vein injection group was significantly higher than in intraperitoneal injection group at each time point (all P < 0.05). There were fewer cleaved Caspase-3⁺, Fas⁺ and FasL⁺ cells in both intraperitoneal and caudal vein injection groups than that in MCAO group 24 hours and 72 hours after IR (all P < 0.05). Meanwhile, there were significantly fewer cleaved Caspase-3⁺, Fas⁺ and FasL⁺ cells in caudal vein injection group than in intraperitoneal group (all P < 0.05).

Melatonin therapy by both intraperitoneal and caudal vein injection could alleviate the expression of cleaved Caspase-3, Fas and FasL proteins in the cerebral cortex in rats after cerebral ischemia reperfusion and protect the neurons from injury, and had neuroprotective effects, and the therapeutic effect by caudal vein injection was better than by intraperitoneal injection.