Basic fibroblast growth factor increases long-term survival of spinal motor neurons and improves respiratory function after experimental spinal cord injury.
Acute focal injection of basic fibroblast growth factor (FGF2) protects ventral horn (VH) neurons from death after experimental contusive spinal cord injury (SCI) at T8. Because these neurons innervate respiratory muscles, we hypothesized that respiratory deficits resulting from SCI would be attenuated by FGF2 treatment. To test this hypothesis we used a head-out plethysmograph system to evaluate respiratory parameters in conscious rats before and at 24 hr and 7, 28, and 35 d after SCI. Two groups of rats (n = 8 per group) received either FGF2 (3 microg) beginning 5 min after injury or vehicle (VEH) solution alone. We found significantly increased respiratory rate and decreased tidal volume at 24 hr and 7 d after SCI in the VEH-treated group. Ventilatory response to breathing 5 or 7% CO(2) was also significantly reduced. Recovery took place over time. Respiration remained normal in the FGF2-treated group. At 35 d after injury, histological analyses were used to compare long-term neuron survival. FGF2 treatment doubled the survival of VH neurons adjacent to the injury site. Because the number of surviving VH neurons rostral to the injury epicenter was significantly correlated to the ventilatory response to CO(2), it is likely that the absence of respiratory deficits in FGF2-treated rats was caused by its neuroprotective effect. Our results demonstrate that FGF2 treatment prevents the respiratory deficits produced by thoracic SCI. Because FGF2 also reduced the loss of preganglionic sympathetic motoneurons after injury, this neurotrophic factor may have broad therapeutic potential for SCI.
Teng
Y D
YD
Department of Cell Biology, School of Medicine, Georgetown University, Washington, DC 20007, USA.
Mocchetti
I
I
Taveira-DaSilva
A M
AM
Gillis
R A
RA
Wrathall
J R
JR
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000032:analysis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006614:Hindlimb; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects
D016222:Fibroblast Growth Factor 2; D002795:Choline O-Acetyltransferase