Circulating insulin-like growth factor I and functional recovery from spinal cord injury under enriched housing conditions

被引:57
作者
Koopmans, GC [1 ]
Brans, M
Gómez-Pinilla, F
Duis, S
Gispen, WH
Torres-Aleman, I
Joosten, EAJ
Hamers, FPT
机构
[1] Univ Maastricht, European Grad Sch Neurosci EURON, Div Neurosci,Sect Cellular Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
[2] Univ Med Ctr Utrecht, Dept Pharmacol & Anat, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands
[3] Univ Calif Los Angeles, Brain Injury Res Ctr, Div Neurosurg, Dept Physiol Sci, Los Angeles, CA USA
[4] Brain Res Inst, Los Angeles, CA USA
[5] CSIC, Inst Cajal, Neuroendocrinol Lab, E-28002 Madrid, Spain
[6] Univ Limburg, Acad Hosp Maastricht, Dept Anesthesiol, Maastricht, Netherlands
关键词
central pattern generator; enriched environment; exercise; gait analysis; rat;
D O I
10.1111/j.1460-9568.2006.04627.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Voluntary locomotor training as induced by enriched housing of rats stimulates recovery of locomotion after spinal cord injury (SCI). Generally it is thought that spinal neural networks of motor- and interneurons located in the ventral and intermediate laminae within the lumbar intumescence of the spinal cord, also referred to as central pattern generators (CPGs), are the 'producers of locomotion' and play a pivotal role in the amelioration of locomotor deficits after SCI. It has been suggested that locomotor training provides locomotor-specific sensory feedback into the CPGs, which stimulates remodeling of central nervous system pathways, including motor systems. Several molecules have been proposed to potentiate this process but the underlying mechanisms are not yet known. To understand these mechanisms, we studied the role of insulin-like growth factor (IGF) I in functional recovery from SCI under normal and enriched environment (EE) housing conditions. In a first experiment, we discovered that subcutaneous administration of IGF-I resulted in better locomotor recovery following SCI. In a second experiment, detailed analysis of the observed functional recovery induced by EE revealed full recovery of hindlimb coordination and stability of gait. This EE-dependent functional recovery was attenuated by alterations in the pre-synaptic bouton density within the ventral gray matter of the lumbar intumescence or CPG area. Neutralization of circulating IGF-I significantly blocked the effectiveness of EE housing on functional recovery and diminished the EE-induced alterations in pre-synaptic bouton density within the CPG area. These results support the use of IGF-I as a possible therapeutic aid in early rehabilitation after SCI.
引用
收藏
页码:1035 / 1046
页数:12
相关论文
共 59 条
[1]  
AHMED S, 1995, J NEUROSCI, V15, P5765
[2]   Visualizing synapse formation in arborizing optic axons in vivo:: dynamics and modulation by BDNF [J].
Alsina, B ;
Vu, T ;
Cohen-Cory, S .
NATURE NEUROSCIENCE, 2001, 4 (11) :1093-1101
[3]   STRUCTURE AND PLASTICITY OF NEWLY FORMED ADULT SYNAPSES - A MORPHOMETRIC STUDY IN THE RAT HIPPOCAMPUS [J].
ANTHES, DL ;
LEBOUTILLIER, JC ;
PETIT, TL .
BRAIN RESEARCH, 1993, 626 (1-2) :50-62
[4]   RECOVERY OF LOCOMOTION AFTER CHRONIC SPINALIZATION IN THE ADULT CAT [J].
BARBEAU, H ;
ROSSIGNOL, S .
BRAIN RESEARCH, 1987, 412 (01) :84-95
[5]   The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats [J].
Bareyre, FM ;
Kerschensteiner, M ;
Raineteau, O ;
Mettenleiter, TC ;
Weinmann, O ;
Schwab, ME .
NATURE NEUROSCIENCE, 2004, 7 (03) :269-277
[6]   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
[7]   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
[8]  
BONDY CA, 1991, J NEUROSCI, V11, P3442
[9]   Contribution of cutaneous inputs from the hindpaw to the control of locomotion. I. Intact cats [J].
Bouyer, LJG ;
Rossignol, S .
JOURNAL OF NEUROPHYSIOLOGY, 2003, 90 (06) :3625-3639
[10]   Contribution of cutaneous inputs from the hindpaw to the control of locomotion. II. Spinal cats [J].
Bouyer, LJG ;
Rossignol, S .
JOURNAL OF NEUROPHYSIOLOGY, 2003, 90 (06) :3640-3653