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),whereas the difference between MM group (15.0 ± 6.6) and Con group was statistically insignificant (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.
ABSTRACT
<p><b>OBJECTIVE</b>In vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain.</p><p><b>METHODS</b>We conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning.</p><p><b>RESULTS</b>Compared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning.</p><p><b>CONCLUSION</b>The present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.</p>