[Effects of lidocaine on brain damage induced by transient global cerebral ischemia in mice of different apolipoprotein E genotypes].
OBJECTIVE
To evaluate the effects of lidocaine on changes of neuropathological outcome as well as the learning and memory abilities induced by transient global cerebral ischemia in mice of different apolipoprotein E genotypes.


METHODS
Transient global ischemia was induced by bilateral common carotid arteries occlusion (BCCAO) for a period of 17 minutes. Healthy male C57BL/6J wild-type mice (C57 mice) and apolipoprotein E knockout mice (apoE mice) were randomly divided into six groups: C57 control group (n = 15, undergoing sham operation, neither BCCAO was performed nor pharmacologic intervention was given), C57 ischemia group (n = 21, BCCAO for 17 minutes was performed and normal saline was given intraperitoneally), C57 lidocaine group (n = 22, BCCAO for 17 minutes was performed and lidocaine was given intraperitoneally), apoE control group (n = 15, undergoing the same procedure as that of the C57 control group), apoE ischemia group (n = 19, undergoing the same procedure as that of the C57 ischemia group), apoE lidocaine group (n = 16, undergoing the same procedure as that of the C57 lidocaine group). The mice were allowed to recover for 7 days. Twenty-eight mice were randomly selected from these 6 groups for neuropathological studies on the 7 th postoperative day. The percentage of ischemic neurons in the CA1 region of hippocampus was calculated. Morris water maze tasks were performed for the rest mice from the 8 th postoperative day. Mice were tested four times daily for 5 consecutive days. The latency period was recorded and the percentage of effective search strategies were calculated.


RESULTS
(1) The percentage of ischemic neurons in the CA1 region of hippocampus was 0.3% +/- 0.1% in the C57 control group, 19.3% +/- 4.5% in the C57 ischemia group, 36.9% +/- 2.5% in the C57 lidocaine group, 0.6% +/- 0.3% in the apoE control group, 65.5% +/- 2.2% in the apoE ischemia group, and 39.4% +/- 6.5% in the apoE lidocaine group, significantly higher in the ischemia and lidocaine groups than in the corresponding control groups (all P < 0.01), significantly higher in the C57 lidocaine and apoE ischemia groups than in the C57 ischemia group (both P < 0.01), however, significantly lower in the apoE lidocaine group than in the apoE ischemia group (both P < 0.01). (2) The latency period decreased significantly along with the test days in all groups except in the apoE ischemia group (P < 0.05 or 0.01), significantly longer in the ischemia and lidocaine groups than in the corresponding control groups (P < 0.05 or 0.01), significantly longer in the C57 lidocaine group than in the C57 ischemia group on the 3 rd day of test [73.1 (22.1-120.1) s vs. 40.2 (28.4-91.1) s], and in the apoE ischemia group than in the C57 ischemia group on the 3 rd and 4 th days of test [88.2 (41.0-120.1) s vs. 40.2 (28.4-91.1) s, and 78.2 (32.9-120.1) s vs. 46.3 (11.6-81.9) s] (P < 0.05 or 0.01), and, however, significantly shorter in the apoE lidocaine group than in the C57 lidocaine group on the 3rd day of test [39.0 (15.5-103.5) s vs. 73.1 (22.1-120.1) s], and in the apoE lidocaine group than in the apoE ischemia group from the 3 rd to the 5 th days of test [39.0 (15.5-103.5) s vs. 88.2 (41.0-120.1) s, 24.9 (11.8-68.0) s vs. 78.2 (32.9-120.1) s, and 29.1 (6.6-57.2) s vs. 66.3 (14.2-97.0) s respectively] (P < 0.05 or 0.01). (3) The percentage of effective search strategy increased significantly along with the test day in all groups except in the C57 lidocaine and apoE ischemia groups (P < 0.05 or 0.01), significantly lower in the ischemia and lidocaine groups than in the corresponding control groups (P < 0.05 or 0.01), significantly lower in the C57 lidocaine group than in the C57 ischemia group on the 4 th and 5 th days of test [25 (0-50)% vs. 50 (25-75)% and 37.5 (0-75)% vs. 50 (50-100)%], and in the apoE ischemia group than in the C57 ischemia group from the 3 rd to the 5th days of test [25 (0-25)% vs. 50 (25-75)%, 25 (0-25)% vs. 50 (25-75)%, and 25 (0-50)% vs. 50 (50-100)% respectively] (P < 0.05 or 0.01), and, however, significantly higher in the apoE lidocaine group than in the C57 lidocaine group [50 (0-75)% vs. 25 (0-50)% and 50 (25-100)% vs. 37.5 (0-75)%], and in the apoE lidocaine group than in apoE ischemia group [50 (0-75)% vs. 25 (0-25)% and 50 (25-100)% vs. 25 (0-50)%] on the 4 th and 5 th days of test (all P < 0.05).


CONCLUSIONS
Transient global cerebral ischemia causes significant brain damage, which is more severe in the apoE mice than in the C57 mice. Lidocaine significantly worsens the ischemic brain damage in the C57 mice, and, however, significantly alleviates the ischemic cerebral result in the apoE mice.
Song
Ping-ping
PP
Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China.
Wang
Dong-xin
DX
Wang
Pei-yu
PY
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation
D000779:Anesthetics, Local; D001057:Apolipoproteins E; D008012:Lidocaine