Neuroprotective effect of HAMI 3379, a CysLT2R receptor antagonist, on chronic brain injury after focal cerebral ischemia in rats

Cysteinyl leukotrienes induce inflammatory responses by activating receptors namely CysLT(1)R and CysLT(2)R. Recently, the study reported that CysLT(2)R is involved in neuronal injury such as astrocytosis and microgliosis after focal cerebral ischemia in rats, and intracerebroventricular injection of HAMI 3379, a selective CysLT(2)R antagonist, protects against acute brain injury induced by middle cerebral artery occlusion (MCAO) in rats. In this study, the effect of HAMI 3379 is long lasting and related to the formation of a glial scar in rats with cerebral ischemia has been further determined. Focal cerebral ischemia was induced by MCAO. After ischemia, HAMI 3379 (0.1 mg/kg) was injected intraperitoneally for six consecutive days. Neurological deficits and sensorimotor function were determined during 14 days after ischemia. Brain lesion, neuronal injury, macrophage-microglia, and glial scar formation were detected at the end of the experiment. HAMI 3379 improved neurological deficits and holding angles in the inclined board test, ameliorated brain atrophy and lesion, increased neurons density in the ischemic border zone, inhibited microglia activation, and glial scar formation (astrocyte proliferation). Hence, these results have confirmed the long-term neuroprotective effects of HAMI 3379, providing further evidence of the therapeutic potential of HAMI 3379 in the treatment of ischemic stroke.