Collagen containing neurotrophin-3 (NT-3) attracts regrowing injured corticospinal axons in the adult rat spinal cord and promotes partial functional recovery.
During development, neurotrophic factors play an important role in the guidance and outgrowth of axons. Our working hypothesis is that neurotrophic factors involved in the development of axons of a particular CNS tract are among the most promising candidates for stimulating and directing the regrowth of fibers of this tract in the lesioned adult animal. The neurotrophin NT-3 is known to be involved in the target selection of outgrowing corticospinal tract (CST) fibers. We studied the capacity of locally applied NT-3 to stimulate and direct the regrowth of axons of the CST in the lesioned adult rat spinal cord. We also studied the effect of NT-3 application on the functional recovery of rats after spinal cord injury, using the gridwalk test. NT-3 was applied at the site of the lesion dissolved into rat tail collagen type I. Four weeks after spinal cord injury and collagen implantation, significantly more CST fibers had regrown into the collagen matrix containing NT-3 (22 +/- 6%, mean +/- SEM) than into the control collagen matrix without NT-3 (7 +/- 2%). No CST fibers grew into areas caudal to the collagen implant. Despite the absence of regrowth of corticospinal axons into host tissue caudal to the lesion area, functional recovery was observed in rats with NT-3 containing collagen implants.
Houweling
D A
DA
Department of Neurology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, 3508 GA, The Netherlands.
Lankhorst
A J
AJ
Gispen
W H
WH
Bär
P R
PR
Joosten
E A
EA
D000818:Animals; D001369:Axons / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D020933:Neurotrophin 3; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D003094:Collagen