Functional recovery after central infusion of α-melanocyte-stimulating hormone in rats with spinal cord contusion injury

被引:44
作者
Lankhorst, AJ
Duis, SEJ
ter Laak, MP
Joosten, EAJ
Hamers, FPT
Gispen, WH
机构
[1] Univ Utrecht, Rudolf Magnus Inst Neurosci, Dept Med Pharmacol, NL-3584 CG Utrecht, Netherlands
[2] Univ Utrecht Hosp, Res Lab Neurol, Utrecht, Netherlands
关键词
alpha MSH; functional recovery; intrathecal administration; melanocortins; motor evoked potentials; spinal cord injury; spontaneous recovery;
D O I
10.1089/neu.1999.16.323
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Melanocortins, peptides related to alpha-melanocortin-stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH), are known to improve axonal regeneration following peripheral nerve injury and stimulate neurite outgrowth from central nervous system (CNS) neurons both in vitro and in vivo. The neurite outgrowth promoting capacity of alpha MSH has prompted us to investigate the effects of intrathecal application of alpha MSH on functional and electrophysiological recovery in a well-characterized model of spinal cord contusion injury. Different doses of alpha MSH were applied via osmotic minipumps into the cisterna magna for 10 days, thereby delivering the peptide directly into the CNS, Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie, and Bresnahan locomotor rating scale, and the thoracolumbar height test, At the end of the study, electrophysiological analysis of rubrospinal motor evoked potentials as performed. Our data showed that application of 3.75 mu g/kg/h alpha MSH resulted in a marked functional recovery, accompanied by a decrease in the latency of the rMEP. This study demonstrates that intrathecal application of alpha MSH results in functional recovery after spinal cord contusion injury, These findings may initiate new treatment strategies and/or the use of melanocortins in human spinal cord injury.
引用
收藏
页码:323 / 331
页数:9
相关论文
共 42 条
[1]  
Azmitia EC, 1987, PROG BRAIN RES <D>, V72, P311
[2]   PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO MELANOCORTINS [J].
BANKS, WA ;
KASTIN, AJ .
PEPTIDES, 1995, 16 (06) :1157-1161
[3]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[4]   Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection [J].
Basso, DM ;
Beattie, MS ;
Bresnahan, JC .
EXPERIMENTAL NEUROLOGY, 1996, 139 (02) :244-256
[5]   [NLE4,D-PHE7]ALPHA-MSH IMPROVES FUNCTIONAL RECOVERY IN RATS SUBJECTED TO DIENCEPHALIC HEMISECTION [J].
BENELLI, A ;
ZANOLI, P ;
BOTTICELLI, A ;
BERTOLINI, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 150 (03) :211-219
[6]   STIMULATION BY ACTH4-10 OF NERVE-FIBER REGENERATION FOLLOWING SCIATIC-NERVE CRUSH [J].
BIJLSMA, WA ;
JENNEKENS, FGI ;
SCHOTMAN, P ;
GISPEN, WH .
MUSCLE & NERVE, 1983, 6 (02) :104-112
[7]   NEUROTROPHIC FACTORS AND REGENERATION IN THE PERIPHERAL NERVOUS-SYSTEM [J].
BIJLSMA, WA ;
JENNEKENS, FGI ;
SCHOTMAN, P ;
GISPEN, WH .
PSYCHONEUROENDOCRINOLOGY, 1984, 9 (03) :199-215
[8]   A RANDOMIZED, CONTROLLED TRIAL OF METHYLPREDNISOLONE OR NALOXONE IN THE TREATMENT OF ACUTE SPINAL-CORD INJURY - RESULTS OF THE 2ND NATIONAL ACUTE SPINAL-CORD INJURY STUDY [J].
BRACKEN, MB ;
SHEPARD, MJ ;
COLLINS, WF ;
HOLFORD, TR ;
YOUNG, W ;
BASKIN, DS ;
EISENBERG, HM ;
FLAMM, E ;
LEOSUMMERS, L ;
MAROON, J ;
MARSHALL, LF ;
PEROT, PL ;
PIEPMEIER, J ;
SONNTAG, VKH ;
WAGNER, FC ;
WILBERGER, JE ;
WINN, HR .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (20) :1405-1411
[9]   RECOVERY OF FUNCTION AFTER SPINAL-CORD INJURY - MECHANISMS UNDERLYING TRANSPLANT-MEDIATED RECOVERY OF FUNCTION DIFFER AFTER SPINAL-CORD INJURY IN NEWBORN AND ADULT-RATS [J].
BREGMAN, BS ;
KUNKELBAGDEN, E ;
REIER, PJ ;
DAI, HN ;
MCATEE, M ;
GAO, D .
EXPERIMENTAL NEUROLOGY, 1993, 123 (01) :3-16
[10]   Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76