| Objective: To establish a suitable and stable rat model of chronic hydrocephalus by stereotactic injection of kaolin saline suspension into the lateral ventricle,and to further explore the pathophysiological mechanism of neurocognitive dysfunction caused by hydrocephalus,so as to provide theoretical basis for basic and clinical research of hydrocephalus.Methods: Sixty adult male SD rats were randomly divided into experimental group(Kaolin group,n=30),sham operation group(Saline group,n=15)and blank control group(Control group,n =15).The rats in the Kaolin group were stereotaxically injected with 50μl of 3 % sterilized kaolin saline suspension into the lateral ventricle,and the rats in the Saline group were injected with the same amount of saline into the lateral ventricle and the Control group was not treated.Head MRI was performed on the 28 th day after modeling to determine whether the hydrocephalus model was successfully established.Based on the MRI imaging data,the Evan’s index of each group of rats was calculated according to the formula,and the ventricular volume of the rats was calculated using Image J software.On the30 th day after modeling,Morris water maze test was used to test the spatial learning and memory ability of rats in each group.The neurological dysfunction scores of rats in each group were obtained by modified Garcia scoring method at 24 h,48h,72 h,7d,14 d,21d and 28 d after modeling.The frozen sections of rat brain tissue were made,and the histopathological changes of hippocampal cortex,choroid plexus,ependyma and corpus callosum were observed by HE staining.The experimental data were statistically analyzed using SPSS26.0 statistical software.The measurement data were expressed as mean ± standard deviation(mean ± SD)and plotted using Graph Pad Prism8.0 software.Repeated measures ANOVA was used to analyze the experimental data of water maze positioning navigation.Oneway ANOVA was used to compare the means of multiple samples.When P<0.05,the difference was considered statistically significant.When P<0.01,the difference was considered significant.Results :1.The model of chronic hydrocephalus in SD rats was successfully established by stereotactic injection of sterilized kaolin saline suspension into the lateral ventricle.2.MRI results showed that the ventricles of rats in the Kaolin group were expanded to varying degrees,especially in the lateral ventricle.The ventricular volume of rats in the Kaolin group was significantly higher than that in the Saline group and the Control group,and the difference was statistically significant(P < 0.01);the Evans index of Kaolin group was significantly higher than that of Saline group and Control group(P < 0.01).3.The results of Morris water maze test showed that the hydrocephalus induced by lateral ventricle injection of kaolin suspension significantly reduced the spatial learning and memory ability of rats.The results of the spatial navigation experiment showed that the escape latency of the Kaolin group was significantly longer than that of the Saline group and the Control group,and the difference between the groups was statistically significant(P<0.01).The results of space exploration experiment showed that the time of staying in the target quadrant of Kaolin group was significantly lower than that of Control group and Saline group(P<0.05),and the number of rats crossing the platform in the Kaolin group was significantly reduced,the difference was statistically significant(P < 0.05).4.The results of modified Garcia score showed that the neurological function score of Kaolin group was significantly lower than that of Control group and Saline group(P < 0.05).5.The results of HE staining showed that there were extensive inflammatory cell infiltration in the choroid plexus and subarachnoid space of the lateral ventricle in the Kaolin group.Choroid plexus structure disorder,the ependyma of the lateral ventricle was damaged,the hippocampus was atrophied and thinned,and the number of pyramidal cells in the CA1 and CA3 regions was reduced and arranged irregularly.The corpus callosum was squeezed and stretched,and obvious fiber breakage was observed.There was no abnormality in the morphological structure of brain cells in the Control group and the Saline group.Conclusion:1.In our experiment,a SD rat model of chronic hydrocephalus was successfully established by stereotactic injection of sterilized kaolin saline suspension into the lateral ventricle,which was consistent with the pathogenesis and clinical characteristics of human chronic hydrocephalus.2.Experimental chronic hydrocephalus caused structural changes in the ependyma and choroid plexus of the lateral ventricle in rats,and extensive inflammatory cell infiltration was observed in the choroid plexus.The changes in the normal physiological structure of choroid plexus and the inflammatory response lead to excessive secretion of cerebrospinal fluid,which affects the normal circulation of cerebrospinal fluid in the ventricle and leads to hydrocephalus.3.Chronic hydrocephalus changes the cell structure of hippocampus and corpus callosum through mechanical compression caused by ventricular dilatation,resulting in the loss of neurons in the pyramidal cell layer and the fracture of nerve connections,destroying the integrity of the neural circuit that controls cognition and memory function,leading to neurocognitive disorders. |
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