Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse

被引:135
作者
Huang, W [1 ]
Chen, Y [1 ]
Shohami, E [1 ]
Weinstock, M [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pharmacol, IL-91120 Jerusalem, Israel
关键词
brain oedema; cholinergic mediation; monoamine oxidase-B inhibition; motor function; neuroprotection; spatial memory;
D O I
10.1016/S0014-2999(98)00929-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The potential neuroprotective effects of rasagiline, N-propareyl-1 R-aminoindan, a selective monoamine oxidase-B inhibitor and its inactive enantiomer TVP1022, N-propargyl-1 S-aminoindan were assessed against the sequelae of closed head injury in the mouse, injury was induced in the left hemisphere under ether anaesthesia. Rasagiline (0.2 and 1 mg/kg) or TVP1022 (1 and 2 mg/kg) injected 5 min after injury accelerated the recovery of motor function and spatial memory and reduced the cerebral oedema by about 40-50%, (P < 0.01). The neuroprotective effects on motor function and spatial memory, but not on cerebral oedema, were prevented by scopolamine (0.3 mg/kg). Daily injection of rasagiline (1 mg/kg) from day 3 after injury accelerated the recovery of spatial memory but not motor function. Conclusions: Early administration of rasagiline or TVP1022 can reduce the immediate sequelae of brain injury. The mechanism of action does not appear to involve monoamine oxidase-B inhibition but could be mediated by the maintenance of cholinergic transmission in brain neurons. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:127 / 135
页数:9
相关论文
共 34 条
  • [1] ANSARI KS, 1993, J NEUROSCI, V13, P4042
  • [2] DEVELOPMENT OF HU-211 AS A NEUROPROTECTANT FOR ISCHEMIC BRAIN-DAMAGE
    BIEGON, A
    JOSEPH, AB
    [J]. NEUROLOGICAL RESEARCH, 1995, 17 (04) : 275 - 280
  • [3] COGNITIVE IMPAIRMENT FOLLOWING CLOSED HEAD-INJURY
    CAPRUSO, DX
    LEVIN, HS
    [J]. NEUROLOGIC CLINICS, 1992, 10 (04) : 879 - 893
  • [4] An experimental model of closed head injury in mice: Pathophysiology, histopathology, and cognitive deficits
    Chen, Y
    Constantini, S
    Trembovler, V
    Weinstock, M
    Shohami, E
    [J]. JOURNAL OF NEUROTRAUMA, 1996, 13 (10) : 557 - 568
  • [5] Rivastigmine, a brain-selective acetylcholinesterase inhibitor, ameliorates cognitive and motor deficits induced by closed-head injury in the mouse
    Chen, Y
    Shohami, E
    Constantini, S
    Weinstock, M
    [J]. JOURNAL OF NEUROTRAUMA, 1998, 15 (04) : 231 - 237
  • [6] Finberg JPM, 1998, NEUROREPORT, V9, P703
  • [7] FINBERG JPM, 1998, IN PRESS PARKINSONS
  • [8] Effects of traumatic brain injury on the cholinergic system in the rat
    Gorman, LK
    Fu, K
    Hovda, DA
    Murray, M
    Traystman, RJ
    [J]. JOURNAL OF NEUROTRAUMA, 1996, 13 (08) : 457 - 463
  • [9] Working memory deficits following traumatic brain injury in the rat
    Hamm, RJ
    Temple, MD
    Pike, BR
    ODell, DM
    Buck, DL
    Lyeth, BG
    [J]. JOURNAL OF NEUROTRAUMA, 1996, 13 (06) : 317 - 323
  • [10] PHARMACOKINETIC ASPECTS OF L-DEPRENYL (SELEGILINE) AND ITS METABOLITES
    HEINONEN, EH
    ANTTILA, MI
    LAMMINTAUSTA, RAS
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 56 (06) : 742 - 749