HAMI 3379, a CysLT2 R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats

• Published in: Neuroscience Vol. 291; pp. 53 - 69
• Main Authors: Shi, Q.J, Wang, H, Liu, Z.X, Fang, S.H, Song, X.M, Lu, Y.B, Zhang, W.P, Sa, X.Y, Ying, H.Z, Wei, E.Q
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: Neurology; BBB; DMSO; LTD 4; T-helper 2; MPO; T-helper 1; antagonist; CysLT 1R; ionized calcium-binding adapter molecule 1; IFN-γ; OGD/R; shRNA; short hairpin RNA; CysLTs; IL; Intracerebroventricular; cysteinyl leukotriene receptor 2 (CysLT 2R); CysLT 2R; leukotriene D 4; middle cerebral artery; NeuN; NC; HAMI 3379; cerebrospinal fluid; TH1; glial fibrillary acidic protein; TH2; interferon-γ; TTC; LTE 4; IgG; neuronal nuclear antigen; Blood–brain barrier; negative control; dimethyl sulfoxide; inflammation; cerebral ischemia; CSF; LTC 4; interleukin; oxygen-glucose deprivation/recovery; microglia; cysteinyl leukotriene receptor 2; Iba-1; cysteinyl leukotriene receptor 1; MCAO; immunoglobulin G; leukotriene E 4; leukotriene C 4; MCA; myeloperoxidase; GFAP; TNF-α; tumor necrosis factor-α; i.c.v; cysteinyl leukotrienes; 2,3,5-triphenyltetrazolium chloride; middle cerebral artery occlusion
• ISSN: 0306-4522
• DOI: 10.1016/j.neuroscience.2015.02.002

Highlights • We determined the neuroprotective effect of the CysLT2 R antagonist HAMI 3379. • HAMI 3379 dose- and time-dependently protects rats from ischemic stroke. • The effective dose is 0.1 ∼ 0.4 mg/kg and the therapeutic window is 1 h. • HAMI 3379 has the effects on ischemic brain injury similar to pranlukast. • It selectively attenuates microglia-related post-ischemic inflammation.