Circulating insulin-like growth factor I and functional recovery from spinal cord injury under enriched housing conditions.
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.
Koopmans
Guido C
GC
Department of Psychiatry and Neuropsychology, Section Cellular Neuroscience, Division Neuroscience, European Graduate School of Neuroscience EURON, University of Maastricht, The Netherlands. g.koopmans@np.unimaas.nl
Brans
Maike
M
Gómez-Pinilla
Fernando
F
Duis
Simone
S
Gispen
Willem Hendrick
WH
Torres-Aleman
Ignazio
I
Joosten
Elbert A J
EA
Hamers
Frank P T
FP
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006799:Housing, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000276:immunology; D008124:Locomotion / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D020127:Recovery of Function / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016708:Synaptophysin; D007334:Insulin-Like Growth Factor I