| Posttraumatic stress disorder (PTSD), a psychiatric condition, is a severe sustaining mental and body clinical syndrome that may develop after violent personal assaults, natural or human-caused disasters, accidents, or military combat. Growing evidence showed that the incidence rate of PTSD in the adults succumbed to severe waterlog in Lake Dongting and the survived orphans after the Tangshan earthquake reached 33.89% and 23% respectively. In 2008, the percentage of survivors of the devastating disaster area in the Wenchuan earthquake suffered from the typical PTSD symptom, insomnia, nightmare, flash back, etc., is about 18.4 %, which indicates the intrinsic relation between the PTSD pathogenesis and social reasons. Hence, PTSD has become a great difficulty due to its high morbidity, long course of disease and bad curative effect in the modern medical research.The most dominant feature of PTSD is characterized by intrusive memory. The patients can not help recalling the injured scene easily, which is different from those searching and self extracting the related information from their memory in the normal conditions. They prefer to self extract every element of the traumatic accident including voice, color, scene and so on, which would result in the re-experiencing of trauma. This course shows the intrusive character which would encounter unexpectively flashback and not be refused. These victims always have nightmare concerning the tragic trauma content followed with the continuing, repeating and intensive mental suffering, which shows the solidifying feature. The intrusive memory results in the elevation of vigilance level in patients. They would act as avoidance behavior to avoid the cues or similar events of trauma, which is the key symptom of PTSD and the main differential aspect as compared with the other psychological dysfunctions, i.e., somatization disorder, emotional disturbance, anxiety disorders.Previously, researchers viewed that the representation of PTSD is the disturbance of memory and the start of specific consciousness system. The information processing of PTSD might exhibit the trauma information memory network including the stimuli information of the trauma accident, the cognition information to the trauma and behavioral response information and linking information of stimuli and response. When the cue of the trauma accident activates the network, the information enters into the functional area and initiates the intrusive memory symptom. Then it tries to start avoiding the related information, which results in the formation of avoiding response syndrome. However, these theories remain to be confirmed via the animal experiment where the coding procedure, memory phenomenon and influence factors should be focused from the aspect of information processing. We believe it may help to expand our understanding in the complicated memory phenomenon.The PTSD patients showed the abnormality of the varying neuroelectrical physiological parameters, such as the injured discrimination of noncorrelated stimuli, the enhancement of the stimulating responses to the trauma specific voice and images, the decrease of event related potential (ERP) and the attenuation of electroencephalogram synchronization. All of them suggest that the abnormality of neurotomia structure and function. The present theory demonstrates the lobus frontalis, limbic system (hippocampus, amygdale, septal area, entorhinal area. etc.) nerve circuit may constitute its anatomical basis. Among them, hypothalamus receives the input of multiple sensory systems and advanced cortex, which plays a fundamental role in the integration of various sensory information and the transformation from short-term memory to long-term memory. Brain image analysis indicates that the volume of right hippocampus of the veteran in Vietnam war decreased by 8.0% compared with the normal control. The volume of the left and right hippocampus decreased 26.0% and 22.0% respectively, and there was intrinsic relation between the volume reduction of hippocampus and severity of PTSD symptom, which might also indicate the loss of hippocampus volume is the predisposing factor. Meanwhile, amygdala possesses the extensive and descending fiber projecting to the hippocampus, hypothalamus, and prefrontal lobe, which acts as the center of the emotion information processing. Its basal nucleus is directly related to the emotion. Results from brain images and animal experiments indicate that amygdala may involve in the formation of intrusive memory in PTSD.Hippocampus is the advance center of stress responses. It plays a key role in the emotion, learning and memory. Also, it is the main brain area, which maintains the nerve regeneration in mammals. Growing evidence showed that most of the PTSD patients have not only the psychological changes but pathological changes. As the brain area involving in the learning and memory, hippocampus may have atrophic changes owing to the long-term of PTSD injury. We should further investigate the relation between the intrusive memory of PTSD and pathological changes of hippocampal neurons. Also, the neuronal apoptosis, different from necrosis, may be initiated by various internal (other cell signals) and external agents (chemical, physical, or biological factors). It is also necessary to elucidate whether the non-traumatic external stimuli could finally result in the neuronal apoptosis in hippocampus. We speculate that the imbalance between the proliferation and apoptosis of neurons may be related to the intrusive memory in PTSD.Lycium barbarum polysaccharide (LBP) is an effective extract from Ningxia lycium barbarum. In recent years, more and more researchers found that LBP could regulate the neuroendocrine immune response including immune regulation, anti-aging, liver protection, radiation protection, anti-fatigue, anti-oxidation and anti-tumor. Researches demonstrate that LBP could inhibit the decrease of neurons in Manganese intoxication; improve the ischemia of stroke; promote the clearance of free radicals and neuron protection. Based on these results, we further view that it might play a positive role in PTSD treatment.Our experiment included four parts: (1) Preparation of PTSD animal models and pathological and behavioral evaluation. The shock in enclosed box and single prolonged stress animal models were made. With the help of assessment of behaviors and histomorphology, the enclosed-shock animal model was regarded as the optimal model for the study of intrusive memory; (2) Investigation of apoptosis and regeneration in hippocampus: The pathogenetic relationship between apoptosis and neurogenesis in the dentate gyrus on the intrusive memory was investigated; (3) The characteristics of hippocampal neurons discharge in traditional index and nonlinear method and the role of basal lateral amygdala in PTSD model were recorded; (4) The effects of LBP on the prevention and therapy for the PTSD were also investigated.Results and Conclusion:1.The rats received electric shock in enclosed box exhibited continuous fear state with less body weight, double state motion, behavior related intrusive memory once reentry into the stress box, reduction of exploration, anxiety emotion, defect of cognition, but has no body injury, which is close to the clinical manifestation of PTSD patient. The PTSD animal model with mimic intrusive memory characteristics is similar to the clinical symptom and easy to operate and repeat. We postulated that the subjected rats to shock and restrained space is useful for mimicing human PTSD.2.The BrdU positive cells were located in the hill of hippocampus DG. The number is continuously decreased and no positive cell was found at 4 weeks after stress. The apoptotic rate of cells was more than that of sham group, and the highest rate was at 1 week after stress. There is negtive relationship between the number of BrdU positive cells and the apoptosis rate of cells in hippocampus DG. The volume of hippocampus reduced 11.7% compared to the sham group. These results suggest that the PTSD animal model has long-standing stress causing the changes of the neurogenesis and apoptosis in hippocampus, and the hippocampus volume is sensitive to the stress.3.The data recorded from the spontaneous discharges of hippocampal neurons in the flashback condition exhibited that the pyramidal cells change in the firing rate, ISI complexity, irregularity and favored pattern, while the interneurons were sensitive to the stress and had no favored pattern.4.The pyramidal cells and interneurons showed increased ISI complexity and favored pattern after bilateral basal lateral amygdala lesion. These changes suggest that the basal lateral amygdala might play a role in the promotion and regulation on the intrusive memory, and there is a short cut between the hippocampus and amygdala.5.The treatment of LBP by intragastric administration in pre-stress (10 mg/kg) and post stress (20 mg/kg) has obvious effect on the behaviors and neurogenesis.The rats received pre-stress treatment showed alleviation on the pathological and behavioral damage than the PTSD rats. The rats received post-stress treatment exhibited the amelioration of cognition defect, alleviation of the apoptosis in hippocampus and recovery for the neurogesis. These results suggest that the LBP treatment might help prevent the severe stress and be useful for the PTSD recovery. |
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