Effects of ulinastatin, a urinary trypsin inhibitor, on synaptic plasticity and spatial memory in a rat model of cerebral ischemia/reperfusion injury.

Abstract

Established therapies for cerebral ischemia-reperfusion injury are currently limited. The urinary trypsin inhibitor ulinastatin (UTI) is considered cytoprotective against ischemia-reperfusion injury in internal organs through its anti-inflammatory activity. We aimed to investigate the neuroprotective effects of UTI on learning and memory of rats after cerebral ischemia-reperfusion injury. Rats were treated with UTI at 10,000 U/kg body weight, then underwent ischemia and reperfusion by the middle cerebral arterial occlusion (MCAO) method. At various times after the onset of reperfusion, we evaluated neurologic impairment scores. Brain sections underwent immunohistochemical staining for synaptophysin and calcium-binding protein S100β. Other rats underwent the Morris water maze test to determine the effects of UTI on learning and memory. Spatial reference learning and memory were improved with UTI treatment by down-regulating S100β-positive cells and preventing the loss of neural cells. Thus, UTI has a neuroprotective role on synaptic plasticity and spatial memory with cerebral ischemia-reperfusion injury in rats.