Effects of piracetam on chronic epilepsy in childhood rats and quantitative effects on content of acetylcholine and activity of cholinacetyltranslase in hippocampus in learning-memory complex animal model

Shaodan ZHANG; Ming YU; Lin PEI; Haibin LI

ABSTRACT

BACKGROUND:

Cholinergic system projected in brain and hippocampal structure is relevant with learning and memory. Piracetam acts on protecting and repairing cerebral neural cell, resisting cerebral functional injury due to physical and chemical factors and improving learning-memory capacity.

OBJECTIVE:

Chronic epilepsy in childhood animal and learning-memory complex animal model were self-prepared to observe the changes in content of acetylcholine and activity of cholinacetyltranslase in cerebral hippocampus and the intervention of piracetam.

DESIGN:

Randomized control experiment and non-blind evaluation were designed.

SETTING:

Department of Pediatrics of Second Hospital of Hebei Medical University and Institute of Traditional Chinese Medicine of Hebei Medical UniversityMATERIALS The experiment was performed in Hebei Medical University and College of Life Sciences of Hebei Normal University from July to December 2004, in which, 50 Wistar childhood rats of clean grade and either sex were employed.

METHODS:

Coriamyrthin injection was administrated muscularly to duplicated chronic epileptic grand mal model in rats. Muscular injection was repeated once every three days. During modeling, those with general paroxysmal convulsion with posterior extremities standing or falling with standing or general stiffness-paroxysmal attack continuously for 3 times, the injection was changed to be once every 14 days. Ten rats were selected to be in normal control without modeling. The rest 40 rats after 3 months of modeling were randomized into 4 groups, named piracetam of 2.4 g/'L group (Group A), piracetam of 4.8 g/L group (Group B), dilantin 6 g/L +piracetam 4.8 g/L group (Group C) and model group (Group D), 10 rats in each. In each group, gastric infusion was performed continuously in 3 months after modeling, once per day, 10 mL/kg. In Group A and Group B,piracetam mixed solution of 2.4 g/L and 4.8 g/L was administrated for infusion respectively. In Group C, dilantin 6 g/L and piracetam 4.8 g/L were infused. In group D and the control group, normal saline 10 mL/kg was administrated. Relevant index determination was done 1 month after medication. Morris water maze test was performed to discover platform time and searching distance of epileptic rats, continuously for 3 days, twice per day. After test, the rats were sacrificed to collect brains to determine the content of acetylcholine in bilateral hippocampus. The activities of cholinacetyltranslase and acetylcholinesterase were determined with radioimmunity method.of acetylcholine in bilateral hippocampus and the activities of cholinacetyltranslase and acetylcholinesterase of rats in each group.ing platform time of rats in every group the corresponding average searching time in Group D was increased compared with the control group [(63±11) s, (40±8) s; (61±9) s, (38±7) s; (57±8) s, (36±9) s; (55±11) s,(33±10) s; (52±7) s, (30±9) s; (49±9) s, (27±6) s, P ＜ 0.01]. In Group C and Group B, the searching time of 6 tests was decreased of various degrees compared with Group D [(44±9) s, (45±9) s;(43±9) s, (42±8) s; (42±7) s,(42±7) s; (40±9) s, (39±9) s; (38±7) s, (35±9) s; (35±6) s, (34±8) s,t=2.352-4.029, P ＜ 0.05-0.01]. In every medication group, the average searching time was decreased gradually by the increased frequency of erage searching distance in Group D was remarkably increased compared with the control [(793±74) cm, (420±81) cm;(763±89) cm, (418±57) cm;(690±67) cm, (382±69) cm; (623±81) cm, (356±71) cm;(592±98) cm,(330±69) cm;(550±54) cm,(301±97) cm,P＜ 0.01]. In Group C and Group B, the average searching distance of 6 tests was decreased of various degrees compared with Group D [(586±91) cm, (510±89) cm;(566±70) cm,(497 ±76) cm; (521 ±84) cm, (455 ±56) cm; (480 ±74) cm, (421 ±63) cm;(437±51) cm, (396±79) cm;(392±79) cm, (385±48) cm, t=2.364-4.230, P ＜ 0.05-0.01]. In every medication group, the average searching distance tent of acetylcholine in brain hippocampus and the activities of cholinacetyltranslase and acetylcholinesterase of rats in each group those in Group D were all remarkably reduced compared with the control [(2.2±0.7) nmol/g,(3.8±0.9) nmol/g;(503.3±103.3) pkat/g, (778.3±125.0) pkat/g;(190.0±51.7) μkat/g, (368.3±86.7) μkat/g, P ＜ 0.01]. In mixed group and Group B, the content of acetylcholine and activity of acetylcholinesterase were remarkably higher than the Group D [(2.7±0.6) nmol/g, (2.9±0.6) nmol/g;(256.7±58.3) μ kat/g, (306.7±88.3) μkat/g, t=3.445-4.148, P ＜ 0.01]. In Group B, the activity of cholinacetyltranslase [(668.3±118.3) kat/g] was remarkably higher than those in the Group D(P ＜ 0.01). Every index in group A was basically same as model group.

CONCLUSION:

Grand mal of chronic epileptic rat model is characterized as declined capacity of spatial learning and memory and associated with decreased content of acetylcholine and the activities of cholinacetyltranslase and acetylcholinesterase in brain hippocampus, explaining the successful complex model of learning and memory disturbance. Piracetam 4.8 g/L may increase content of acetylcholine and the activities of cholinacetyltranslase and acetylcholinesterase in brain hippocampus and improve learning-memory capacity, but its effect at 2.4 g/L was not remarkable.