Combination of olfactory ensheathing cells with local versus systemic cAMP treatment after a cervical rubrospinal tract injury.
The failure of CNS axons to regenerate following traumatic injury is due in part to a growth-inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery after spinal cord injury. However, in our previous experiments, OEC transplants failed to promote regeneration of rubrospinal axons through and beyond the site of a dorsolateral funiculus crush in rats. Rubrospinal neurons undergo massive cell atrophy and limited expression of regeneration-associated genes after axotomy. Using the same injury model, we tested the hypothesis that treatment of the red nucleus with cAMP, known to stimulate the intrinsic growth response in other neurons, will promote rubrospinal regeneration in combination with OEC transplants. In addition, we assessed a systemic increase of cAMP using the phosphodiesterase inhibitor rolipram. OECs prevented cavity formation, attenuated astrocytic hypertrophy and the retraction of the axotomized rubrospinal axons, and tended to reduce the overall lesion size. OEC transplantation lowered the thresholds for thermal sensitivity of both forepaws. None of our treatments, alone or in combination, promoted rubrospinal regeneration through the lesion site. However, the systemic elevation of cAMP with rolipram resulted in greater numbers of OECs and axonal density within the graft and improved motor performance in a cylinder test in conjunction with enhanced rubrospinal branching and attenuated astrocytic hypertrophy.
Bretzner
Frederic
F
ICORD-International Collaboration On Repair Discoveries, Blusson Spinal Cord Centre, Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
Plemel
Jason R
JR
Liu
Jie
J
Richter
Miranda
M
Roskams
A Jane
AJ
Tetzlaff
Wolfram
W
D000818:Animals; D001369:Axons / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods*; D000242:Cyclic AMP / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D009068:Movement / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010812:Physical Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D020889:Rolipram / Q000627:therapeutic use; D012583:Schwann Cells / Q000637:transplantation*; D012684:Sensory Thresholds / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013223:Statistics as Topic
D005904:Glial Fibrillary Acidic Protein; D010726:Phosphodiesterase Inhibitors; D049452:Green Fluorescent Proteins; D000242:Cyclic AMP; D020889:Rolipram