title: [Effect of lidocaine on the impairment of learning and memory function and central cholinergic system after transient global cerebral ischemia in mice].
abstract: OBJECTIVE
  To evaluate the effects of lidocaine on the impairments of learning and memorial function and central cholinergic system after 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 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 (sham operation, neither BCCAO was performed nor pharmacologic intervention was given), C57 ischemia group (BCCAO for 17 minutes was performed and normal saline was given intraperitoneally), C57 lidocaine group (BCCAO for 17 minutes was performed and lidocaine was given intraperitoneally), ApoE control group (the same procedure as that of C57 control group), ApoE ischemia group (the same procedure as that of C57 ischemia group), ApoE lidocaine group (the same procedure as that of C57 lidocaine group). The mice were allowed to recover for 7 days. Morris water maze test were performed from the 8th postoperative day. Mice were tested four times daily for 5 consecutive days. The latency periods were recorded and the percentages of effective search strategies were calculated. On the 12th postoperative day after Morris water maze test, mice were decapitated under anesthesia. The cerebral cortex and hippocampus were removed quickly. The activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) as well as the binding activity of muscarinic receptor (M receptor) were assayed.
  
  
  RESULTS
  (1) The latency periods were significantly longer in the ischemia groups than in the corresponding control groups (P<0.05 or 0.01). They were also significantly longer in C57 lidocaine group than in C57 ischemia group [on the 3rd day of test, (74.1+/-32.7)s vs (49.2+/-19.5)s] (P<0.05). However, they were significantly shorter in apoE lidocaine group than in apoE ischemia group [from the 3rd to the 5th days of test, (40.7+/-27.7)s vs (84.7+/-26.8)s, (31.2+/-19.2)s vs (72.1+/-33.0)s, and (28.0+/-22.1)s vs (60.8+/-26.9)s, respectively] (P<0.05 or 0.01). When compared between two strains, they were significantly longer in apoE ischemia group than in C57 ischemia group (P<0.05 or 0.01). However, they were significantly shorter in apoE lidocaine group than in C57 lidocaine group (P<0.01). (2) The percentages of effective search strategies were significantly lower in the ischemia groups than in the corresponding control groups (P<0.01). They were also significantly lower in C57 lidocaine group than in C57 ischemia group [from the 3rd to the 5th days of test, (18.2+/-11.7)% vs (41.7+/-17.7)%, (22.7+/-20.8)% vs (55.6+/-20.8)%, and (29.6+/-27.0)% vs (66.7+/-21.7)%, respectively] (P<0.01). However, they were significantly higher in apoE lidocaine group than in apoE ischemia group [from the 3rd to the 5th days of test, (41.7+/-25.8)% vs (15.6+/-12.9)%, 8.3+/-20.4)% vs (18.8+/-11.6)%, and (66.7+/-30.3)% vs (28.1+/-20.9)%, respectively] (P<0.01). When compared between two strains, they were significantly lower in apoE ischemia group than in C57 ischemia group (P<0.01). However, they were significantly higher in apoE lidocaine group than in C57 lidocaine group (P<0.01). (3) The parameters of central cholinergic system were significantly lower in the ischemia groups than in the corresponding control groups (P<0.05 or 0.01). They were also significantly lower in C57 lidocaine group than in C57 ischemia group [the activities of AChE of cerebral cortex and hippocampus, (0.44+/-0.09) U/mg protein vs (0.57+/-0.08) U/mg protein, and (0.73+/-0.21) U/mg protein vs (1.08+/-0.27) U/mg protein, respectively; the activities of ChAT of hippocampus, (80.60+/-6.55) pmol/mg protein/min vs (93.66+/-11.15) pmol/mg protein/min; and the binding activities of M receptor of cerebral cortex and hippocampus, (6.03+/-0.74) pmol/mg protein vs (7.49+/-0.48) pmol/mg protein, and (7.56+/-0.92) pmol/mg protein vs (10.65+/-3.35) pmol/mg protein, respectively] (P< 0.05 or 0.01). However, they were significantly higher in ApoE lidocaine group than in ApoE ischemia group [the activities of ChAT of cerebral cortex and hippocampus, (66.99+/-7.55) pmol/mg protein/min vs (46.23+/-4.96) pmol/mg protein/min, and (116.46+/-24.05) pmol/mg protein/min vs (92.08+/-16.33) pmol/mg protein/min, respectively] (P<0.05 or 0.01). When compared between two strains, they were significantly higher in ApoE lidocaine group than in C57 lidocaine group (P< 0.05 or 0.01).
  
  
  CONCLUSIONS
  Transient global cerebral ischemia caused significant brain damages in both strains of mice, which were represented by decline of learning and memorial function and damage of the central cholinergic system. Compared with the C57 mice, the ApoE mice had enhanced susceptibility to global cerebral ischemic injury as shown by more severe decline of the learning and memorial function. In the C57 mice, lidocaine significantly worsened the ischemic brain damage. In the ApoE mice, however, lidocaine significantly alleviated the ischemic cerebral results.
authors.affiliation: Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Song
authors.forename: Dong-xin
authors.initials: DX
authors.lastname: Wang
authors.forename: Pei-yu
authors.initials: PY
authors.lastname: Wang
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Zuo
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000523:psychology*; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D011976:Receptors, Muscarinic; D008012:Lidocaine; D000110:Acetylcholinesterase