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The Experimental Study of Cognition Alteration of Rats with Different Medicine after Middle Cerebral Artery Occlusion
Author: LiuChunYu
Tutor: ChenKangNing
School: Third Military Medical University
Course: Neurology
Keywords: Middle cerebral artery occlusion Vascular cognitive dysfunction Cholinesterase inhibitors Serotonin reuptake inhibitors Monoamine neurotransmitters
CLC: R749.1
Type: Master's thesis
Year: 2006
Downloads: 82
Quote: 0
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Abstract
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BACKGROUND AND PURPOSE: Ischemic cerebrovascular disease is a serious harm to human health and survival of the disease, hemiplegia and cognitive dysfunction caused by ischemic cerebrovascular disease affect the quality of human existence, the biggest obstacle. Clinical cerebral artery occlusion due to cerebral infarction accounted for the vast majority of ischemic cerebrovascular disease. Past people tend to attach importance to the cause of the nerve of the middle cerebral artery occlusion (middlecerebral artery occlusion, MCAo) function (eg: hemiplegia) disorders, vascular cognitive impairment after MCAO less attention (the vascular cognitive exposure exposure VCI). Patients with vascular cognitive impairment is increasing year by year, seriously affecting the quality of life of patients. VCI to drug treatment, including acetylcholinesterase (AChE) inhibitor. But these drugs with toxic side effects, and costly drawbacks, it is difficult to commonly used in clinical practice. It is particularly important to find an effective drug treatment of vascular cognitive impairment. 5 - serotonin and monoamine neurotransmitter memory close relationship in recent years, attention has gradually been. Studies have shown that the clinical application of 5 - serotonin reuptake inhibitors (SSRIs) drugs can be effective in improving cognitive dysfunction citalopram of SSRIs, but the effect of citalopram improve post-stroke cognitive disorder unclear. Longa method improved in this experiment replication MCAo model animal, the observed cognitive function changes, while giving donepezil hydrochloride (Donepezil), citalopram (Cipramil) two drugs intervention, observation of the two drugs on MCAo animal Cognitive function change explore the effect of middle cerebral artery occlusion and cognitive dysfunction, comparative study of two different pharmacological effects of drugs on the role of the middle cerebral artery occlusion cause cognitive dysfunction, aims to provide the basis for clinical VCI intervention method : Zea Longa method Improved copy MCAo model animal, 126 SD rats were randomly divided into 7 groups (n = 18): sham operation group (A), ischemia 30min control group (Ba group), ischemia 30min hydrochloric multi donepezil intervention group (of Ca group), ischemia 30min citalopram intervention group (Da group), ischemia 90min control group (Bb group) 90min hydrochloride donepezil intervention group (Cb group) of ischemia, ischemia 90min citalopram intervention Group (Db group), to 1.65mg/kg.d hydrochloride donepezil, 6.25mg/kg.d citalopram citalopram administered orally for 14 days. Sham group, the control group rats each 2ml / d saline gavage, which lasted the same time. After two weeks of treatment, the brain made of brain slices, TTC staining observed infarct. Applications classic Morris water maze test, detection of event-related potentials P300 latency changes observed changes in cognitive function in rats after treatment. Detection of rat hippocampal monoamine neurotransmitter changes observed cognitive dysfunction in rat hippocampal monoamine neurotransmitter changes in judge two drugs interventions hippocampal monoamine neurotransmitters. Immunohistochemical staining rat hippocampal cholinergic neurons of the damage, as well as changes after the intervention. Results: 1 rat P300 latency changes: sham-operated rats P300 latency is 250.00 ± 12.71ms ischemia 90min, 30min control group rats P300 latency was significantly longer than the sham group (P <0.01). The P300 latency ischemia 30min two drug intervention group their control rats compared to no significant difference (P> 0.05), comparison between ischemic 30min two drug intervention group is no significant difference (P> 0.05). Ischemia 90min two drug intervention P300 latency in their control group of rats rats were significantly shortened (P <0.01), hydrochloric donepezil group rat P300 latency was significantly shorter than citalopram rats (P <0.01). Ischemia 90min control group, citalopram hydrochloride donepezil group and its corresponding ischemia the 30min group compared to the P300 latency was significantly longer (P <0.01, P <0.05). 2, the average water maze test in rats escape the incubation period of the change: ischemia 90min, 30min control group rats average escape latency of the sham group was significantly longer (P <0.01, P <0.05). Ischemia 30min two drug intervention group escape latency to their control group no significant difference (P> 0.05). Ischemia 90min drug intervention group and its control group was significantly shorter (P <0.01). Experimental days 3,4,5 ischemia 90min hydrochloride donepezil group (P <0.05) was significantly shorter mean escape latency citalopram group. Ischemia 90min control group hydrochloride donepezil group, citalopram group average escape latency of its corresponding ischemia 30min group were significantly prolonged compared (P <0.01). 3, platform quadrant swimming time of rats, and the percentage of total swimming time (t P / t T) changes: ischemia 90min, 30min control group rats were significantly less than the sham group (P <0.01 t P / t T percentage P <0.05). Ischemia 30min two drug intervention group t P / t T a percentage of their control group no significant difference (P> 0.05). Ischemia 90min percentage value of the two-drug intervention group their control group compared to a significant increase (P <0.05), hydrochloric donepezil group tP / tT was significantly greater than in the citalopram group (P <0.05). Ischemia 90min control group hydrochloride donepezil group, citalopram group t P / t T ratio were significantly smaller than the corresponding ischemia 30min group (P <0.05, P <0.01) rats platform quadrant swimming distance and accounting changes in the total percentage of swimming distance (d P / d T): ischemia 90min, 30min control group rats d P / d T percentage is significantly less than the sham group (P <0.01, P <0.05). Ischemia 30min two drug intervention group d P / d T a percentage of their control group had no significant difference (P> 0.05). Ischemia 90min percentage value of the two-drug intervention group and its control group compared to a significant increase (P <0.05), and hydrochloric donepezil group d P / d T is significantly larger than the citalopram group (P <0.05). Ischemia 90min control group, donepezil hydrochloride, citalopram group d P / d T ratios are significantly smaller than its corresponding ischemic 30min group (P <0.05, P <0.01) 5, Hippocampus monoamine recursive qualitative change: ischemia 90min, 30min control group hippocampus NE, DA and 5-HT content with the sham surgery group compared to the significantly lower (P <0.05). Ischemia 30min two drug intervention group rat hippocampus of NE, DA and 5-HT content also showed a lower trend but compared to their control group had no significant difference (P> 0.05), and there is no obvious difference between the two drug intervention group (P> 0.05). Ischemia 90min two drug intervention group rat hippocampus NE ,5-HT and DA content was significantly higher than the control group (P <0.01, P <0.05), and hydrochloric donepezil group hippocampal NE, DA and 5-HT content citalopram group was significantly higher (P <0.05, P <0.01). Ischemic of 90min the control group, hydrochloric donepezil group and the citalopram group hippocampus NE, DA and 5-HT content was significantly lower (P <0.05, P <0.01) than the corresponding ischemia 30min group. 6, rat ChAT immunohistochemical staining of change: Immunohistochemical staining was found the sham group hippocampal cholinergic neurons densely arranged, regular in shape. Control rats hippocampal cholinergic neurons arranged sparse, disorder, and cholinergic neurons appear pyknosis and cell structure is unclear changed, lesser severity of ischemia a 30min control group rats ischemia 90min pathological degree of control rats. Ischemia 90min two drug intervention group hippocampal cholinergic neurons with ischemic 90min according rats increased significantly, and the hydrochloride the donepezil group citalopram rats hippocampal cholinergic neurons also increased significantly. Conclusion: middle cerebral artery occlusion can cause cognitive decline, and with the ischemia time, the more severe the damage cognitive function. 2, two drug intervention can be varying degrees of improvement in cognitive dysfunction. Different ischemic brain artery occlusion-induced cognitive dysfunction, the results of two drugs intervention vary. Hydrochloride donepezil intervention for cognitive dysfunction caused by ischemia 90min greater degree of cognitive improvement, better than citalopram drug intervention. Ischemia a 30min lead to cognitive dysfunction, the two drugs did not differ significantly improve the efficacy of the intervention on cognitive function. The mechanism of action of two different modes of intervention may improve hippocampal neuron structure / function.
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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Cerebral organic mental disorder
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