Repetitive intrathecal VEGF(165) treatment has limited therapeutic effects after spinal cord injury in the rat.
Neuropathic pain and motor deficits are detrimental consequences of injury to the spinal cord. In experimental settings, numerous neuroprotective agents are being explored for their therapeutic benefits. Vascular endothelial growth factor (VEGF) is an interesting candidate molecule in this respect since it is not only associated with angiogenesis, but also with neuroprotection and neurite growth. Other investigators have reported improved motor outcomes following intraparenchymal VEGF treatment. Here we demonstrate the therapeutic effects of daily intrathecal treatment of the contused thoracic rat spinal cord with the 165-isoform of VEGF during the first week after injury. We show that VEGF treatment resulted in a statistically significant attenuation of mechanical, but not thermal, hypersensitivity of the hindpaws, while motor deficits remained unaffected. Tissue sparing was also unchanged by VEGF treatment. Microglial responses at the lumbar spinal cord, which have been linked with spinal cord injury-induced hypersensitivity, were found to be unaffected by VEGF treatment. We conclude that repetitive intrathecal VEGF delivery has limited therapeutic effects on spinal cord injury outcome.
van Neerven
Sabien
S
Department of Anesthesiology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Joosten
Elbert A J
EA
Brook
Gary A
GA
Lambert
Charles A
CA
Mey
Jörg
J
Weis
Joachim
J
Marcus
Marco A
MA
Steinbusch
Harry W
HW
van Kleef
Maarten
M
Patijn
Jaap
J
Deumens
Ronald
R
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007278:Injections, Spinal; D009043:Motor Activity / Q000502:physiology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use*
D005904:Glial Fibrillary Acidic Protein; D042461:Vascular Endothelial Growth Factor A