OBJECTIVE To observe the neurotoxicity of 1-bromopropane(BP) and investigate the protective effects of edaravone(Edv) against BP-induced deficits of spatial learning and memory ability in rats by its anti-inflammatory mechanism. METHODS Adult male Wistar rats were ig given BP 800 mg·kg-1 to develop the model, followed by Edv 1, 3 and 5 mg·kg-1 ip treatment respectively 4 h later for consecutive 12 d. From the 7th day (d 7), all rats were subjected to the five-day place navigation in Morris water maze (MWM) to measure the escape latency and the total swimming distance. On d 6 of MWM, spatial probe test was performed and the crossing times of rats were recorded to evaluate the spatial memory ability. At the end of the behavioral experiment, four rats in each group were randomly selected and the frozen section of the whole brain was sliced for thionin staining and immunohisto?chemistry. The other eight sacrifced rat brains from each group were harvested for the determination of the tumor necrosis factor-α (TNF-α) and nitric oxide (NO) by ELISA and nitrate reductase method, respectively. RESULTS The results of MWM test showed that compared with control rats the escape latencies of rats in BP group were increased by 60.8%, 81.9%,124.0% and 323.3%, respectively, during the d 2-d 5 of MWM, and the total swimming distance increased by 47.0%, 66.4%, 106.0% and 277.6%, respectirely. All the differences between BP group and control group were significant (P<0.05, P<0.01). In the spatial probe trial, the crossing times of rats in BP group were significantly decreased, compared with the control rats (P<0.01). Morphologically, thionin staining and immunohistochemistry revealed significant microglia activation and neuron loss in the rat forebrains, accompanied by a 147.6% and 18.7% increase in NO and TNF-α levels in rats treated with BP respectively compared with control values (P<0.05, P<0.01). After co-treatment at different dosages of Edv with BP, the escape latencies of rats in BP+Edv 5 mg·kg-1 group were decreased by 38.4%and 44.3%(P<0.01), and the total swimming distance decreased 34.5%and 43.3%(P<0.05, P<0.01), respectively, compared with the BP treated rats on the d 4 and d 5 of MWM test. The microglia activation and neuron damage in the brain of rats induced by BP treatment were significantly alleviated in BP+Edv groups. In addition, the contents of NO and TNF-α were decreased in BP+Edv 1, 3 and 5 mg · kg-1 groups, with a decrease of 53.8%, 55.4% and 59.8% in NO, and 12.2%, 15.8% and 22.2% in TNF-α(P<0.05, P<0.01), respectively. CONCLUSION Edv could effectively protect against central neurotoxicity induced by BP via anti-neuro?inflammation.

Objective:To observe the role of neuroinflammation in cognitive dysfunction induced by 1-bromopropane (1-BP) in rats.Methods:Male Wistar rats were randomly divided into control group, 1-BP group, pyrrolidine dithiocarbamate(PDTC)+ 1-BP group and PDTC group, with 15 rats in each group. Rats in 1-BP group and PDTC+ 1-BP group were given 800 mg / kg 1-BP by gavage, and rats in control group and PDTC group were given equal volume corn oil once a day for 12 days; rats in PDTC group and PDTC+ 1-BP group were intraperitoneally injected with 100 mg / kg PDTC 30 minutes after gavage, while rats in control group and 1-BP group were injected with equal volume of normal saline once a day for 12 days.From the 7th to 12th day of the experiment, ten rats in each group were randomly selected and subjected to Morris water maze test for detect the cognitive function. In the positioning navigation test, the learning ability of rats was evaluated by the escape latency and total swimming distance respectively. In the space exploration experiment, the memory ability of experimental animals was evaluated by the number of times crossing the target platform. After the experiment, ten rats were sacrificed, the cerebral prefrontal cortex was harvested. The cytosolic and nuclear NF-κB expression and phosphorylation were detected by Western blot, the mRNA levels of TNF-α and IL-1β were detected by qRT-PCR. After cardiac perfusion fixation, the brains of 5 rats were taken to make frozen sections for immunohistochemical staining and Nissl staining. SPSS 20.0 software was used for statistical analysis, repetitive measurement deviation analysis was used for the analysis of the swimming distance and the escape latency in positioning navigation test, One-way ANOVA was used for the analysis of the number of times crossed the target platform in spatial probe test and other data. Tukey's test was used for Post hoc comparison.Results:The results of Morris water maze showed that there was significant interaction between group and training time in the total swimming distance of rats in the four groups ( F=3.762, P<0.05). Simple effect analysis showed that the total swimming distance of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the total swimming distance of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). There was significant interaction between group and training time in the escape latency among the four groups ( F=6.541, P<0.01). The escape latencies of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the escape latencies of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). The results of space exploration experiment showed that there was significant difference in the number of crossing the platform among the four groups ( F=75.333, P<0.01). The number of crossing the platform (1.08±0.29) in 1-BP group was lower than that in the control (3.35±0.05) ( P<0.01). The number of crossing the platform (1.95±0.26) in PDTC+ 1-BP group was higher than that in 1-BP group ( P<0.01). It had significant difference both in the cytoplasm and in the nucleus of the NF-κB protein level in prefrontal cortex among rats of the four groups ( F=20.865, 23.877, both P<0.01). The levels of NF-κB in cytoplasm and nucleus of rats in 1-BP group were both higher than those in control group (cytoplasm: (177.3±32.1)%, (100.0±8.4)%, P<0.01; nucleus: ( 173.2±27.1)%, (100.0±8.4)%, P<0.01). While the levels of NF-κB in cytoplasm and nucleus of 1-BP+ PDTC group were both lower than those of 1-BP group (cytoplasm: (148.7±22.0)%, (177.3±32.1)%, P<0.01; nucleus: (149.7±18.8)%, (173.2±27.1)%, P<0.01). The results of qRT-PCR showed that there were significant differences in the mRNA levels of TNF-α and IL-1β in the prefrontal cortex among the four groups ( F=17.464, 17.382, both P<0.01). The levels of TNF-α and IL-1β mRNA in 1-BP group were higher than those in control group (both P<0.05), and the levels of TNF-α and IL-1β mRNA in PDTC+ 1-BP group were both lower than those in 1-BP group (both P<0.05). The results of immunohistochemistry showed that compared with the control group, the number of microglia and astrocytes in the 1-BP group increased (microglia: (158.30±9.68), (110.20±16.30), P<0.05; astrocytes: (122.76±4.35), (80.24±6.96), P<0.05), and the morphology was also activated, with light staining and reduced number of Nissl bodies in neurons.The number of microglia and astrocytes in PDTC + 1-BP group was lower than that in 1-BP group (microglia: (131.70±14.67), (158.30±9.68), P<0.05; astrocytes: (101.54±4.55), (122.76±4.35), P<0.05), and the Nissl body staining of neurons was significantly deepened. Conclusion:NF-κB signaling pathway might be the key mechanism of 1-BP neurotoxicity. PDTC intervention could significantly improve the neuroinflammatory response and behavioral disorders of experimental animals intoxicated with 1-BP.