Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.
Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. Female Sprague-Dawley rats (n = 55) sustained a 10-g weight-drop injury to the lower thoracic spinal cord (T10) from a height of 12.5 mm using the NYU impactor. A micro-infusion system (Alzet minipump) was used to continuously deliver drugs or vehicle directly into the epicenter of the contused spinal cord starting 1 or three h postinjury. At the end of 7 days, animals were perfused and the cords removed for histopathological analysis. Longitudinal serial sections were cut on a freezing microtome and stained with cresyl violet. Areas of central necrosis, partial preservation, and total zone of tissue injury were identified and traced by an independent reviewer using a computer based imaging system. The mean total zone of injury in five animals receiving vehicle infusion was 18.04+/-4.20 mm3. The mean zone of partial preservation in these animals was 16.46+/-3.32 mm. Basic fibroblast growth factor reduced the total zone of injury by 33% [p<0.01, least significant difference (LSD) of Fisher] in five animals and the zone of partial preservation by 32% (p<0.01, LSD of Fisher) when compared to controls. There were trends toward reduction in total zone of injury and zone of partial preservation in rats treated with IL-4, CNTF, and NGF versus vehicle; however, none of these reached statistical significance. No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.
Lee
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TT
Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami School of Medicine, Florida, USA. TLee@Mednet.med.miami.edu
Green
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BA
Dietrich
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WD
Yezierski
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RP
D000818:Animals; D020934:Ciliary Neurotrophic Factor; D003288:Contusions; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007263:Infusions, Parenteral; D007378:Interleukins / Q000008:administration & dosage / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D020934:Ciliary Neurotrophic Factor; D007378:Interleukins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2