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

Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their receptors, CysLT1R and CysLT2R. We recently reported that CysLT2R is involved in neuronal injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Here, we determined whether HAMI 3379, a selective CysLT2R 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 24 h of reperfusion. HAMI 3379 (1, 10 or 100 ng) was injected intracerebroventricularly (i.c.v.) 30 min before MCAO, and the CysLT1R antagonist pranlukast (0.1 mg/kg, i.p.) was used as a positive control. HAMI 3379 at 10 and100 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 CysLT2R antagonists in the treatment of ischemic stroke.

► We determined effect of the CysLT2R antagonist HAMI 3339 on acute brain ischemia.
► Intracerebroventricular HAMI 3379 inhibited brain injury 24 h after MCAO.
► Effect of HAMI 3379 was similar to that of the CysLT1R antagonist pranlukast.