Cannabinoids inhibit neurodegeneration in models of multiple sclerosis

被引:269
作者
Pryce, G
Ahmed, Z
Hankey, DJR
Jackson, SJ
Croxford, JL
Pocock, JM
Ledent, C
Petzold, A
Thompson, AJ
Giovannoni, G
Cuzner, ML
Baker, D
机构
[1] UCL, Inst Neurol, Dept Neuroinflammat, London WC1N 1PJ, England
[2] Free Univ Brussels, Inst Rech Interdisciplinaire Biol Humaine & Mol, Brussels, Belgium
[3] UCL, Inst Neurol, Neurorehabil Grp, London, England
关键词
cannabinoids; excitotoxicity; experimental allergic encephalomyelitis; multiple sclerosis; neuroprotection;
D O I
10.1093/brain/awg224
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB(1) tolerate inflammatory and excito toxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB(1) agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.
引用
收藏
页码:2191 / 2202
页数:12
相关论文
共 71 条
[1]   Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis [J].
Achiron, A ;
Miron, S ;
Lavie, V ;
Margalit, R ;
Biegon, A .
JOURNAL OF NEUROIMMUNOLOGY, 2000, 102 (01) :26-31
[2]   A role for caspase-1 and-3 in the pathology of experimental allergic encephalomyelitis -: Inflammation versus degeneration [J].
Ahmed, Z ;
Doward, AI ;
Pryce, G ;
Taylor, DL ;
Pocock, JM ;
Leonard, JP ;
Baker, D ;
Cuzner, ML .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 161 (05) :1577-1586
[3]  
Arévalo-Martin A, 2003, J NEUROSCI, V23, P2511
[4]   Endocannabinoids control spasticity in a multiple sclerosis model [J].
Baker, D ;
Pryce, G ;
Croxford, JL ;
Brown, P ;
Pertwee, RG ;
Makriyannis, A ;
Khanolkar, A ;
Layward, L ;
Fezza, F ;
Bisogno, T ;
Di Marzo, V .
FASEB JOURNAL, 2001, 15 (02) :300-302
[5]   INDUCTION OF CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN BIOZZI MICE [J].
BAKER, D ;
ONEILL, JK ;
GSCHMEISSNER, SE ;
WILCOX, CE ;
BUTTER, C ;
TURK, JL .
JOURNAL OF NEUROIMMUNOLOGY, 1990, 28 (03) :261-270
[6]   Cannabinoids control spasticity and tremor in a multiple sclerosis model [J].
Baker, D ;
Pryce, G ;
Croxford, JL ;
Brown, P ;
Pertwee, RG ;
Huffman, JW ;
Layward, L .
NATURE, 2000, 404 (6773) :84-87
[7]   THE LONGSTANDING MS LESION - A QUANTITATIVE MRI AND ELECTRON-MICROSCOPIC STUDY [J].
BARNES, D ;
MUNRO, PMG ;
YOUL, BD ;
PRINEAS, JW ;
MCDONALD, WI .
BRAIN, 1991, 114 :1271-1280
[8]  
Bjartmar C, 2000, ANN NEUROL, V48, P893, DOI 10.1002/1531-8249(200012)48:6<893::AID-ANA10>3.3.CO
[9]  
2-2
[10]   Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis [J].
Black, JA ;
Dib-Hajj, S ;
Baker, D ;
Newcombe, J ;
Cuzner, ML ;
Waxman, SG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (21) :11598-11602