| Objective:Morris water maze experiment was used to observe the changes of the learning and memory ability of rats with chronic migraine(CM)and the effect of Cerebralcare Granule(CG)on the learning and memory ability in CM rats.And observe the changes of monoamine neurotransmitters serotonin(5-HT)and dopamine(DA)in rat brain tissue,to discuss the influence of CM on cognitive function and the effect of CG on CM related cognitive function changes,explore the possible mechanism leading to cognitive function changes by CM and provide basis for preventing and treating cognitive impairment leading by CM clinically.Methods:Forty-eight healthy clean-grade male Sprague Dawley rats were selected and all rats underwent a surgery that a micro cannula implanted epidurally.After three days of prophylactic treatment with antibiotics,they were randomly divided into two groups: control group and experimental group,twenty-four rats in each group.The control group was divided into blank control(CON)group and drug control group which is Cerebralcare Granule(CG)group,twelve rats in each group.The experimental group was divided into chronic migraine group that is inflammatory soup group(IS group)and drug intervention group that is inflammatory soup+Cerebralcare Granule group(IS+CG group)of twelve each.The model of rats with chronic migraine was prepared by epidural repeated infusion of inflammatory soup(IS).2uL inflammatory soup were slowly pumped into the dural surface of rats daily by micro-helix quantitative propulsion device.The behavior of rats was observed within half an hour after infusion.Modelling is successful when exploration behavior,freezing behavior,resting behavior,face-grooming and body-grooming behavior occur frequently.The same dose of phosphate buffer solution was infused into the dural surface of rats in the control group.The IS+CG and CG groups were given high dose of Cerebralcare Granule solution(0.32g/ml,1ml/100 g,intragastric[i.g.]),and the CON and IS groups were given the same dose of saline(i.g.).The learning and memory ability of the rats in each group was evaluated by Morris water maze experiment after one or two weeks of continuous administration.The prefrontal cortex of the rats was dissected after evaluated,and the content of 5-HT,DA in the brain tissue of each group was determined by enzyme-linked immunosorbent assay(ELISA).Results:(1)Behavioral observation showed that the rats in the experimental group appeared nociceptive behaviors such as exploration behavior frequently within half an hour after infusion of inflammatory soup.With the increase of repeated infusion times of inflammatory soup,the frequency and time of nociceptive behaviors in rats with CM increased.Until one week passed,the occurrence time of nociceptive behavior in rats tended to be stable,which meanings a CM model has been successful done.(2)The positioning navigation trial showed that the escape latency of rats in IS and IS+CG groups was longer than that in CON group(P<0.05),and the escape latency in IS+CG group was shorter than that in IS group significantly(P<0.05).Compared the second week's IS group to the first week's,the escape latency of rats was significantly different(P<0.05).There was no significant difference in IS+CG group in the first and the second weeks,so as to CG and CON groups.(3)The probe trial showed that compared to CON group,the times of IS groups crossing the platform area within 180 s decreased significantly(P<0.05),and the exploration time in the target quadrant decreased significantly(P<0.05).While the IS+CG group improved but did not differ significantly compared to the IS group.There was no significant difference between the CG and the CON groups.(4)The biochemical analyses of the prefrontal cortex revealed a significant decrease(P<0.05)in 5-HT and DA levels both in the IS and IS+CG groups compared to the CON group,and the decrease of IS group was more obvious than that of IS+CG group(P<0.05).The concentrations of 5-HT(P<0.05)and DA in IS group decreased further with the duration of migraine.There was no significant difference in IS+CG groups in the first and the second weeks,so as to CG and CON groups.Conclusion:(1)Morris water maze experiment showed that CM rats still kept normal learning and memory patterns,but their learning and memory abilities were worse than those of normal rats.With the duration of migraine,their learning and memory abilities decreased further.The preventive and therapeutic effects of Cerebralcare Granule can improve the learning and memory abilities of rats,but its effect is limited,and prolonging the medication time will not significantly increase the curative effect.(2)The biochemical analysis of the prefrontal cortex showed that CM influenced the learning and memory ability was positively correlated with the 5-HT and DA levels.Cerebralcare Granule can improve the learning and memory ability of rats by improving two neurotransmitter levels,and its preventive effect is greater than therapeutical effect. |
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