Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion.
- Author:
Hao WANG
1
;
Honggang GUO
2
;
Qi LOU
2
;
Qiaojuan SHI
2
Author Information
1. Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
2. Laboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Behavior, Animal;
drug effects;
Brain Injury, Chronic;
drug therapy;
Brain Ischemia;
Gerbillinae;
Leukotriene Antagonists;
pharmacology;
therapeutic use;
Neuroprotective Agents;
pharmacology;
therapeutic use;
Random Allocation;
Receptors, Leukotriene;
metabolism;
Reperfusion Injury;
drug therapy
- From:
Journal of Zhejiang University. Medical sciences
2018;47(1):19-26
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:: To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism.
METHODS:: Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method.
RESULTS:: CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all <0.01); Pranlukast and HAMI 3379 also significantly improved the behavioral function 14 days after reperfusion(<0.05 or <0.01). Compared with saline group, the neurological symptom scores in Pranlukast and HAMI 3379 groups presented a trend of amelioration 14 d after reperfusion, but it was not significant(>0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all <0.01).
CONCLUSIONS:: CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.
