BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats.
Although regeneration of injured axons is inhibited within the adult CNS, moderate recovery can be found in patients and animals with incomplete spinal cord injury (SCI). This can be partly attributed to sprouting of spared and injured axons, rostral and caudal to the lesion, respectively. Recently, it has been reported that following a thoracic SCI such sprouting can result in indirect reconnections of the lesioned axons to caudal targets via propriospinal interneurons (PrI). Here, we attempted to further promote this spontaneous repair mechanism by applying the neurotrophic factor BDNF (brain-derived neurotrophic factor), in the vicinity of the cell bodies of lesioned corticospinal neurons or NT-3, intrathecally to the cervical spinal cord. We performed a dorsal over-hemisection at the thoracic spinal cord sparing only the left ventrolateral quadrant. This type of lesion did not promote sprouting of injured corticospinal axons or re-routing via commissural PrI. Also, in rats that received NT-3 at the cervical enlargement, no increase in sprouting was found. However, animals receiving BDNF at the cell bodies of lesioned corticospinal neurons showed a significant increase in collateral sprouting and in the number of contacts with PrI. This was not observed when BDNF was administered to unlesioned animals. Although no statistical difference in the horizontal ladder walking was found between the groups, the increase in collateral sprouting and in the number of contacts correlated with the functional recovery. Hence, cell body treatment can promote plasticity of the injured CNS and may be a valuable treatment approach in conjunction with local regeneration promoting strategies.
Vavrek
R
R
University of Alberta, Faculty of Rehabilitation Medicine, Edmonton, Alberta, Canada.
Girgis
J
J
Tetzlaff
W
W
Hiebert
G W
GW
Fouad
K
K
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D002574:Cervical Vertebrae / Q000473:pathology; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013904:Thoracic Vertebrae / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor