The prophylactic and therapeutic effects of montelukast on delayed neuropsychologic sequelae after acute carbon monoxide poisoning in rat model

Abstract

Objective o investigate the prophylactic and therapeutic effects of montelukast, a cysteinyl leukotriene receptor-1 (CysLT1R) antagonist, on the delayed neuropsychological sequelae (DNS) in rat model of carbon monoxide (CO) poisoning and to explore the possible underlying mechanism. Methods A total of 90 rats were acclimated for one week prior to screening rat by Morris water maze test. Ten rats were randomly assigned to control group (Con group), and the remaining 80 rats were subjected to modified method of intraperitoneal injection of CO gas to establish animal model of acute CO poisoning, Thereafter, the survival rats randomized into CO poisoning group (Mod group), low-dose montelukast group (ML group), medium-dose montelukast group (MM group), high-dose montelukast group (MH group) (n=10 each). Montelukast was accordingly administered via intragastric tube at different intervals (30 min, 4 h and 12 h) after CO poisoning, and then montelukast was administered every 12 hours for 7 consecutive days. The rats of control group and Mod group received equal volume of normal saline instead at given intervals. Twenty-one days after CO exposure, the average escape latency was measured by Morris water maze test to screen DNS rats followed by H-E staining to observe the pathological changes of cortex and hippocampal CA1 region and TUNEL was used to assess the apoptosis of neurons in cortex and hippocampal CA1 region after rats sacrificed. Results All CO-exposed rats exhibited cognition function lowered, and the escape latency (seconds) in Mod group (43.3 ± 15.5), ML group (31.5 ± 13.2) and MH groups (30.1 ± 12.2) was significantly prolonged compared with Con group (12.1 ± 3.0) (P 0.05). Compared with Mod group, the escape latency in montelukast treatment groups was shortened, whereas the significant difference in escape latency only found between Mod group and MM group (P < 0.05). Except for Con group, DNS was evident in CO-exposed groups, and the numbers of DNS rats in Mod, ML, MM and MH groups were 8, 5, 1, 4, respectively, which made statistically significant differences to Con group (P< 0.05) except MM group. The DNS incidence in MM group was lower than that in Mod group (P < 0.05). Mod group exhibited severe histopathological injury to the brain, with evident apoptosis of neural cells, whereas in the groups with montelukast treatment, histopathological damage to the brain was mitigated and the number of apoptotic neuronal cells was diminished noticeably in MM group. Conclusion Montelukast can ameliorate the cognitive function of rats, decrease the incidence of DNS and reduce the apoptosis of neural cells as well as attenuate neuronal cell injury, thus exerting neuroprotection against DNS in rats with CO poisoning. Key words: Montelukast; Cysteinyl leukotriene receptor-1; Rat; Carbon monoxide poisoning; Delayed neuropsychologic sequelae; Morris water maze; Escape latency; Neuronal apoptosis