Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene receptor 2 antagonist, protects against acute brain injury after focal cerebral ischemia in rats

Abstract

Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their receptors, CysLT(1)R and CysLT(2)R. We recently reported that CysLT(2)R is involved in neuronal injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Here, we determined whether HAMI 3379, a selective CysLT(2)R antagonist, protects against acute brain injury after focal cerebral ischemia in rats. We induced transient focal cerebral ischemia by 30 min of middle cerebral artery occlusion (MCAO), followed by 24h of reperfusion. HAMI 3379 (1, 10 or 100 ng) was injected intracerebroventricularly (i.c.v.) 30 min before MCAO, and the CysLT(1)R antagonist pranlukast (0.1mg/kg, i.p.) was used as a positive control. HAMI 3379 at 10 and 100 ng (but not at 1 ng) attenuated the neurological deficits, and reduced infarct volume, brain edema, IgG exudation, neuronal degeneration and neuronal loss. This protective effect was similar to that of pranlukast. Thus, HAMI 3339 at 10-100 ng i.c.v. is neuroprotective against acute brain injury after focal cerebral ischemia in rats. These findings suggest therapeutic potential for CysLT(2)R antagonists in the treatment of ischemic stroke.