| Background:Stroke is the second leading cause of death in the world.The 2015 data shows that there are approximately 16 million new stroke patients each year in the world.In addition to high mortality and disability rates,stroke can cause insomnia,memory dysfunction,and mood disorders and gradually developed into post-stroke depression(PSD),post-stroke anxiety disorder(PSAD)and vascular dementia(VaD).If not given timely treatment,mental disorders after stroke will hinder function recovery,causing great pain and burden on the patients and their families.Due to its common and complex clinical manifestations,it is difficult to detect and diagnose in the early stages,resulting in delays in treatment.Therefore,the study of mental disorders after stroke requires the attention of many domestic and foreign scholars.As there is no more advance achieved in studies on etiology about genetics,pathology and biology,imaging technology,with rapid development,enables morphology and functional status of central nervous system visualized.Currently,functional imaging studies on PSAD are not as many as studies on VaD and PSD,as well as no study on the process of stroke developing into VaD,PSAD and PSD.Therefore,the study targets on this problem.Objective:Using the method of animal in vivo experiments,Yi-nao-jie-yu decoction is used as an intervention method to observe the changes of metabolism and nerve fibers in different brain regions during the development from cerebral hemor-rhage to PSD,PSAD and VaD,from the perspective of neural function around prefrontal cortex and hippocampus,and the role of Yi-nao-jie-yu decoction in different phases of mental disorders after stroke.The significance of combined application of functional magnetic resonance imaging(fMRI)in the early diagnosis of mental disorders after stroke is explored,in order to provide research ideas for clinical diagnosis and treatment.Methods:Male Wistar rats were randomly divided into control CONT,intracerebral hemorrhage group,sham-operated group,intracerebral hemorrhage group,PSD model group,PSD sham operation group,and PSD Chinese medicine group,PSAD model group,PSAD sham group,PSAD Chinese medicine group,VaD model group and VaD Chinese medicine group.The model of hemorrhagic stroke was established by the injection of collagenase into caudate-putamen nucleus.The intracerebral hemorrhage model group and sham-operated group were given distilled water gavage for 7 days.The intracerebral hemorrhage group was given Chinese medicine gavage for 7 days.After that,these groups were tested by structural MRI and fMRI.Seven days after cerebral hemorrhage surgery,the PSAD model was prepared with indeterminate empty vials,and PSD model was prepared with chronic unpredictable mild stimulation.The 22nd days after surgery,the hemorrhagic VaD model was selected by a step-down experiment.The sham operation group and the model group were given distilled water,and the Chinese medicine group was given Yi-nao-jie-yu decoction by,and the stomach was continuously fed for 4 weeks.Changes in behavior were observed dynamically at three time points,in the first,second,and fourth week after gavage administration.After gavage,structural MRI,magnetic resonance spectroscopy,diffusion tensor imaging and arterial spin labeling were used to observe brain metabolism,nerve fibers and cerebral perfusion in the relevant regions of pre-frontal cortex and hippocampus.Results:1.Morphology and Behavioral results(1)Morphology results:After the empty bottle stimulation,PSAD rats showed obvious aggressive behavior,gnaw the cage,reduced modification behavior(combing fur and washing face),standing hairs,messy and dull hair,and eating less.After the model,PSD group rats showed signs of tiredness,yellowish hair,dull luster,crouching in the corners,indifference and loose stools.In the VaD model group,the spontaneous activity decreased,combing frequency decreased,hair was dull,and inquiry behavior decreased.Compared with the model group,the PSAD Chinese medicine group showed that the modification behavior of the rat increased,the aggressive behavior was significantly reduced,and the hair was smoother than before,but was less than normal group.After 4w of drug intervention,the overall state of rats in the PSD,PSAD,and VaD groups was improved compared with the model group,but it was still lower than the normal group.(2)Behavioral results of PSD:The body weight of rats in the PSD model groups was significantly lower than that of rats in the sham-operated group(P<0.01),and the body weight of the rats in the PSD Chinese medicine groups was not significantly higher than that in the model group(P<0.05).In the first,second,and fourth weeks,the sucrose water consumption of the rats in the PSD model group was significantly reduced(P<0.01),and the consumption of sucrose in the rats of the traditional Chinese medicine group was increased compared with the model group at the three time points(P<0.01).In open-field test,the total scores of the PSD model group were significantly reduced in the first,second and forth weeks(P<0.05,P<0.01).When the Chinese medicine group was compared with the model group,the increase in scores was observed in the fourth weeks(P<0.05,P<0.01).(3)Behavioral results of PSAD:In the second and forth weeks,the body weight of rats in the PSAD model groups was significantly lower than that of rats in the sham-operated group(P<0.01),and the body weight of the rats in the PS AD Chinese medicine groups was significantly higher than that in the model group(P<0.05).Elevated elevated plus-maze showed that the OE/TE and OT/TT values of the PSAD model group decreased significantly in the first,second,and fourth weeks(P<0.05,P<0.01),while the comparison between the Chinese medicine group and the model group was OE/TE.The OT/TT value increased(P<0.05,P<0.01).The results of open-field test were that the total scores of the PSAD model group were significantly reduced than sham-operated group in the second and fourth week(P<0.05,P<0.01).When the Chinese medicine group was compared with the model group,the increase in scores was observed in the fourth weeks(P<0.05,P<0.01).(4)Behavioral results of VaD:There was no significant difference in body weight between the VaD model group and the traditional Chinese medicine group(P>0.05).In Step-down test and Morris water maze experiment,among rats in the VaD model group,the incubation period of the model group was significantly shorter than that of the traditional Chinese medicine group,and the number of errors was significantly increased(P<0.01)in the first,second,and fourth weeks.The initial angle of the rats in the VaD model group was higher than that in the Chinese medicine group in the first and fourth weeks(P<0.05),and the number of crossing the platform was significantly increased in the first,second,and fourth weeks in the Chinese medicine group compared with the model group(P<0.05,P<0.01).2.MRS resultsPSD,PSAD,and VaD all had decreased NAA levels,which were significantly lower than those in the bleeding model group and the sham group(P<0.05,P<0.01).The levels of NAA/Cr were higher in each Chinese medicine group than in the corresponding model group(P<0.05,P<0.01).The relative content of Glu in the left prefrontal cortex(PFC)decreased,while the relative content of Glu in PSAD mainly increased in the right PFC(P<0.05).The levels of Cho/Cr in the PFC on the right side of PSAD decreased,and the levels of Cho/Cr in the PFC on the left side of PSD and VaD decreased(P<0.05,P<0.01).3.Functional magnetic resonance results(1)DTI:The FA values of the right PFC in the PSD,PSAD,and VaD model groups were significantly lower than those in the normal group,cerebral hemorrhage model group,cerebral hemorrhage sham operation group,and cerebral hemorrhage Chinese medicine group(P<0.05,P<0.01).The FA value of the left PFC in PSAD model group was significantly lower than that of the normal group and cerebral hemorrhage Chinese medicine group(P<0.05).In the VaD,PSAD model group and VaD model group,the FA value was decreased in the right cingulum compared with the normal group,and the FA value in the VaD model group was lower than that in the normal group,the ICH model group,and the ICH group(P<0.05,P<0.01).The FA of PSD,PSAD,and VaD groups was higher than that of the corresponding model group(P<0.05,P<0.01).(2)ASL:The CBF value of the right PFC in the PSAD model group was significantly higher than that in the normal group(P<0.01).The CBF of the bilateral Hp in the VaD model group was lower than that in the normal group(P<0.01).The Chinese medicine group was elevated compared to model group(P<0.05,P<0.01).In the PSD model group,the CBF value of the right PFC was lower than that of the normal group(P<0.01),and the CBF value of the PSD Chinese medicine group was significantly higher than that of the model group(P<0.05).Conclusions:1.Post-stroke depression,anxiety,and dementia model rats showed different behavioral characteristics.In the PSA group,the exploring times increased.The PSD group showed decreased interest and behavioral inhibition.The VaD group showed a decrease in learning and memory.The Yi-nao-jie-yu decoction relieves depression,anxiety,and improves memory.2.The important material basis of the development of depression,anxiety,and dementia after stroke is hippocampus and prefrontal cortex.Both hippocampus and pre-frontal cotex have significant changes in PSD,while the changes in right hippocampus and pre-frontal cotex of PSAD rats are signicant.The VaD rats have obvious changes in both hippocampus and pre-frontal cotex,expecially in hippocampi.3.During the development of PSD,PSAD,and VaD,neurons and nerve fiber in the hippocampus,prefrontal cortex,neurotransmitters,neurotransmitters,and cell proliferation were observed.Yi-nao-jie-yu decoction can relieve post-stroke depression,anxiety and dementia by repairing damaged neurons and fiber and regulating neurotransmitters.3.According to the study results above,the combination of multiple functional magnetic resonance imaging methods can be used to better assess the structural and functional changes in depression,anxiety,and dementia after strokes,as well as the therapeutic effect.Innovation:1.For the first time,structural functional magnetic resonance imaging,magnetic resonance spectroscopy,diffusion tensor imaging,and arterial spin labeling imaging have been applied in the study of the development of stroke-to-stroke mental disorders.2.By the intervention of Yi-nao-jie-yu decoction in animal models of mental disorders after stroke,the internal mechanism of traditional Chinese medicine is preliminary explored and the target is sought. |
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