Effect of phenytoin on learning and memory impairment in mice with acute hypobaric hypoxia

Effect of phenytoin on learning and memory impairment in mice with acute hypobaric hypoxia

Acute hypobaric hypoxia can cause brain tissue damage has been confirmed, but there are few reports on the effects of acute hypobaric hypoxia on learning and memory. We used the mouse model of learning and memory impairment (Aeronautical Military Medicine, 1997, 25(4): 20), using mouse jumping and avoiding darkness experiments to affect the learning and memory of mice with acute hypobaric hypoxia induced by diphenylhydantoin (DPH). The dysfunction was observed and the results are reported below.

1 Materials and methods

(1) Materials: 40 Kunming mice, half male and half female, weighing 20-24 g (supplied by Experimental Animal Center of Bethune Medical University), were free to eat under experimental conditions, and were tested after 3 days of adaptation to the environment. DPH (produced by Kaifeng Pharmaceutical Factory of Henan Province) is dissolved in distilled water and promoted by Tween-80 (Tween-80 is a commonly used solubilizer, chemically stable). The animal low-pressure chamber was manufactured by the Air Force Aviation Medical Research Institute. The mouse platform tester, the mouse darkness test automatic recorder, and the mouse self-activity recorder were manufactured by the Institute of Materia Medica, Chinese Academy of Sciences.

(2) Methods: 1 Animal grouping and administration: After weighing, the mice were randomly divided into 4 groups, 10 in each group, namely, normoxia group (no liftoff), hypoxia group (lift off), prevention group (first irrigation) Take DPH 40 mg·kg21, then lift off), the treatment group (first lifted off, then DPH 40 mg·kg21), the normoxic group and the hypoxic group were given the same amount of distilled water. 2 Acute hypobaric hypoxia test: After the DPH was administered to the mice in the prevention group, they were placed in the low-pressure chamber of the animal simultaneously with the other groups (except the control group), and increased to a height of 8 km at a speed of 30 m·s21. The temperature was lowered to the ground at a rate of 30 m·s21, and the treatment group was immediately administered with DPH, and the other groups of mice were given an equal amount of distilled water. The learning and memory function tests of mouse jumping and avoiding darkness were carried out 2 h after the experiment. 3 Mouse platform test: The mice were placed on a safety platform, and the bottom of the box was energized. The latency of the mouse from the stage and the escape to the stage was escaped (escapelatency, EL), and the mice were recorded within 5 minutes. The number of shocks is taken as the number of errors (mistake, M). The academic scores were evaluated according to EL and M. The acute hypobaric hypoxia experiment was performed 24 hours later, and then the platform experiment was repeated, with EL and M as the evaluation indexes of memory function. 4 mice avoid dark experiment: the mice were placed in the dark test instrument, the mice were injected into the dark room with electric shock EL and M, 24 hours after the acute hypobaric hypoxia experiment, and then repeat the dark test, record the shock EL and M were used to evaluate learning and memory functions in mice.

2 Results (1) The effect of the platform test and DPH on the learning and memory function of mice: Compared with the other groups, the mice in the prevention group had poor academic performance, and the expression was EL prolonged and M increased, but there was no statistical difference. After 24 h, the mice were tested for memory function by acute hypobaric hypoxia. The results showed that EL was significantly prolonged in the hypoxic group compared with the other groups (44. 50 ± 20.83) s (P < 0.05). M; increased (3. 30 ± 0. 95) s (P < 0.05), with statistical significance, indicating that acute hypobaric hypoxia can cause significant damage to memory function in mice. (2) Effects of avoiding darkness test and DPH on learning and memory function in mice: It can be seen from Table 1 that the memory ability of the mice in the prevention group and the treatment group was significantly improved compared with the hypoxic group mice, and the expression was M decreased and EL extended. It indicated that a certain dose of DPH had a certain preventive effect on memory impairment caused by acute hypobaric hypoxia; there was no significant difference between M and EL in the treatment group compared with the prevention group (P > 0.05).

3 Discussion Acute hypoxia is an important issue in aeromedical science. The physiological effects of hypoxia on the human body have been extensively studied. The decline of learning and memory is one of the main clinical manifestations of ischemia and hypoxic encephalopathy. DPH is experimental. Cerebral ischemia and hypoxia have protective effects. This experiment shows that the use of animal low-pressure chamber to simulate high-altitude flight can lead to acute hypobaric hypoxia in mice, and the EL to escape from electric shock is prolonged. The EL treatment is shortened and M is increased, which shows memory dysfunction. Prevention and treatment of DPH before and after acute hypobaric hypoxia can alleviate the impairment of memory function in mice. Tip: DPH has a certain preventive effect on memory dysfunction caused by acute hypobaric hypoxia. This may be related to DPH to improve Na+ enzyme activity in brain cell membrane under hypoxia, stabilize cell membrane, reduce brain edema, and increase intracerebral - 5HT, DA content. Wait a certain relationship. Whether DPH plays a role in promoting neurological recovery through other means remains to be further studied.

Key words: phenytoin, hypobaric hypoxia, learning and memory function