Neurobehavioral evaluation method for animal models of vascular cognitive impairment-reference memory
Neurobehavioral evaluation method for animal models of vascular cognitive impairment- reference memory
Since its first introduction in vascular cognitive impairment (VCI) in 1993, it has become the focus of social attention in the past 20 years, and is also a hot topic in the field of neuroscience. The incidence of VCI is increasing year by year, and its incidence is second only to Alzheimer disease (AD). It is one of the important factors that cause dementia in old age and lead to the decline of quality of life in the elderly. Although the clinical research of VCI has made some progress, the pathogenesis and pathophysiological changes of VCI are still unclear. Therefore, more basic research is urgently needed to provide a theoretical basis for the early diagnosis and treatment of VCI.
The biggest difference between clinical research and basic research is that clinical research can directly reflect the cognitive status of patients through various scales such as MMSE and Moca, and the identification of animal cognitive impairment can only be accomplished through various evaluation tools. However, the cognitive evaluation tools reported in the literature and their applications are various, so we analyzed the evaluation methods and their applications commonly used in recent literature, and summarized the common evaluation of the cognitive functions of experimental animals before export. , working memory, etc.
1 reference memory evaluation
Spatial memory impairment is currently the most comprehensive and comprehensive of VCI research. Spatial memory refers to the part of memory that records environmental information and spatial orientation.
1. 1 Morris water maze: The morris water maze (MWM) is an escape platform that uses animal survival instinct to swim in the pool. The evaluation of reference memory usually includes positioning navigation and space exploration. MWM is currently recognized as a more objective evaluation method of learning and memory function in the world. It is mainly due to the short time required for animal training, which is beneficial to the cognitive evaluation in the acute phase. At the same time, clues such as odor in the maze can be eliminated; Animals do not need to fast in the experiment; MWM is more sensitive to learning and memory detection than the radial arm maze, and the reference memory of the experimental animals is found to be impaired when there is no positive detection of the radial arm maze 7 days after cerebral ischemia. Due to the different parameters and exclusion criteria of scholars at home and abroad, although the credibility of the experimental results in recent years as a classical learning and memory evaluation tool has been questioned by domestic and foreign scholars. For example: (1) not suitable for long-term memory function evaluation and repeated experiments, the use of aversion to escape test itself will produce stress, increase confounding factors, increase the risk of false positives; (2) non-cognitive factors, such as mobility, hearing , olfactory, tactile, anxiety and depression may affect the reliability of experimental results; (3) experimental results can not reflect the pathological results well; (4) MWM mainly reflects hippocampal-dependent visual spatial memory function, for severe ischemia (Global cerebral ischemia model) Cognitive defects caused by structures such as damaged cortex and thalamus cannot be reflected. Therefore, Bingham et al. proposed exclusion criteria based on a large number of experiments to eliminate interference from confounding factors.
1. 2 Barnes maze The Barnes maze (Barnes maze BM) is based on the need for MWM to increase false positive rates when animal function is impaired. Because BM has less physical energy consumption for animals, in theory, BM is a feature that uses caries to like the dark environment, and uses spatial positioning information outside the platform as a clue to effectively determine the location of the shelter. Similar to MWM, the experimental process usually involves learning training experiments and exploring experiments. BM does not require food deprivation and foot electric shock, so it is less stressful to animals; the experiment requires little physical strength of the animal, and can minimize the impact of physical decline caused by age on the experimental results; The time is small, and the whole experiment can be completed within 5-10 days according to different experimental schemes. BM is widely used in models such as subcortical vascular dementia causing impaired reference memory/microembolism causing vascular dementia. It not only reflects the damage and regeneration of hippocampal CA1 neurons in vascular cognitive impairment, but also the decrease in the number of synaptic connections between the entorhinal cortex and the dentate gyrus. However, before the occurrence of cognitive dysfunction caused by microemboli, there are already neurological abnormalities such as anxiety and depression. Therefore, the reliability of BM evaluation of spatial learning and memory impairment is also affected by emotional behavior.
1.3 Radial Arm Maze RAM The radial arm mazeRAM was originally designed by Olton and colleagues. Using the visual reference information provided in the room, the position of the arm where the food is placed can be effectively determined. The most commonly used is the 8-arm. maze. A reference memory error is when an animal enters an arm that has never let go of the pellet. In theory, RAM is a task driven by food rewards. The stability of the repeated measurement is good. The main disadvantage is that animals need food deprivation before starting the experiment, and animal and food odors may interfere with the experimental results. Although experimental animals have limited space for selection, RAM is currently considered to be an effective and sensitive tool for testing reference memory and working memory. RAM has been widely used in chronic cerebral ischemia (bilateral common carotid artery occlusion method, four-vessel occlusion method, common carotid artery stenosis model, risk factors-induced cognitive impairment studies, in order to exclude visual impairment interference, in different The arms can be coated with different textures to help the experimental animals navigate. The radial water mazeRAWM used in recent years is similar to the combination of MWM and RAM, combining the advantages of MWM and RAM, so it is more sensitive. Mild cognitive impairment caused by unilateral common carotid artery occlusion was found.
1.4 Active/passive avoidance experiments can be divided into light/dark box avoidance, shuttle avoidance, and platform avoidance according to the different instruments and equipment used. The avoidance experiment mainly reflects the cortical function. So avoidance experiments are technically similar to suggesting associated conditional fears. According to the escape mode of animals, they are divided into active avoidance and passive avoidance (active/passive avoidance). The avoidance experiment is simple and easy to perform, and there are many observation indicators. However, the animal's response is quite different, and attention should be paid to the screening of experimental animals. Since the false positive rate of active avoidance is higher than the false negative rate of passive avoidance, passive avoidance experiments are often used. However, the results of passive avoidance experiments were less correlated with histopathological findings.
Active position avoidance (ac; tive place avoidanc; e} APA) is similar to active avoidance, but can reduce the active avoidance false positive rate. It means that a fixed quadrant on a slowly rotating circular platform is set as the electric shock area, the platform is rotating but the electric shock area is unchanged, the experimental animal avoids the fixed electric shock area by learning, and also uses the experimental animal to aversive stimulation (such as the foot) The electric shock is built up by the fear and memory. It is more complicated than the traditional active avoidance experiment, because the experimental animal needs to ignore the olfactory reference on the turntable and avoid the electric shock by visually observing the distant reference object. The learning memory function is evaluated mainly by the number of electric shocks, and the exercise function is evaluated by the total distance of the exercise. Zhou et al found that APA was more sensitive than passive avoidance in the vascular cognitive impairment model of middle cerebral artery occlusion.
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