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 [J].
BIEGON, A ;
JOSEPH, AB .
NEUROLOGICAL RESEARCH, 1995, 17 (04) :275-280
[3]   COGNITIVE IMPAIRMENT FOLLOWING CLOSED HEAD-INJURY [J].
CAPRUSO, DX ;
LEVIN, HS .
NEUROLOGIC CLINICS, 1992, 10 (04) :879-893
[4]   An experimental model of closed head injury in mice: Pathophysiology, histopathology, and cognitive deficits [J].
Chen, Y ;
Constantini, S ;
Trembovler, V ;
Weinstock, M ;
Shohami, E .
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 [J].
Chen, Y ;
Shohami, E ;
Constantini, S ;
Weinstock, M .
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 [J].
Gorman, LK ;
Fu, K ;
Hovda, DA ;
Murray, M ;
Traystman, RJ .
JOURNAL OF NEUROTRAUMA, 1996, 13 (08) :457-463
[9]   Working memory deficits following traumatic brain injury in the rat [J].
Hamm, RJ ;
Temple, MD ;
Pike, BR ;
ODell, DM ;
Buck, DL ;
Lyeth, BG .
JOURNAL OF NEUROTRAUMA, 1996, 13 (06) :317-323
[10]   PHARMACOKINETIC ASPECTS OF L-DEPRENYL (SELEGILINE) AND ITS METABOLITES [J].
HEINONEN, EH ;
ANTTILA, MI ;
LAMMINTAUSTA, RAS .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1994, 56 (06) :742-749