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A combination of tumor necrosis factor-α and neuronal nitric oxide synthase antibodies applied topically over the traumatized spinal cord enhances neuroprotection and functional recovery in the rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2010 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1199, 175-185 p.Article in journal (Refereed) Published
Abstract [en]

The possibility that neutralization of nitric oxide synthase and tumor necrosis factor alpha (TNF-alpha) in the cord using their antiserum will induce neuroprotection and improve functional outcome following spinal cord injury (SCI) was examined in a rat model. The SCI was induced in rats by a unilateral incision of the right dorsal horn at the T10-11 segments under equithesin anesthesia. TNF-alpha and/or neuronal nitric oxide synthase (nNOS) antibodies were applied over the traumatized spinal cord at 10-90 minutes after injury and functional recovery and cord pathophysiology were examined at five hours. Topical application of TNF-alpha antiserum at 10 min followed by NOS antiserum at 20 min after SCI significantly improved functional recovery and attenuated blood-spinal cord barrier (BSCB) disturbances, edema formation, and cord pathology. These neuroprotective effects were also seen when the NOS antiserum was applied 10 min after injury followed by TNF-alpha antiserum at 30 min after trauma. However, when TNF-alpha antiserum was applied 1 h after injury and NOS antiserum was given either before or after TNF-alpha antiserum, no neuroprotective effects were observed. Interestingly, neuronal injury was tightly correlated with nNOS expression in the cord in antibody treated groups. These novel observations suggest that early blockade of TNF-alpha and nNOS expression within 20-30 min after SCI is beneficial in nature. This indicates that TNF-alpha. and nitric oxide play synergistic roles in the pathophysiology of SCI and combined antibodies therapy has added neuroprotective values in spinal trauma.

Place, publisher, year, edition, pages
2010. Vol. 1199, 175-185 p.
Keyword [en]
spinal cord injury, nitric oxide synthase, tumor necrosis factor alpha, functional outcome, spinal cord pathology, motor disturbances
National Category
Anesthesiology and Intensive Care
URN: urn:nbn:se:uu:diva-136483DOI: 10.1111/j.1749-6632.2009.05327.xISI: 000282838900020OAI: oai:DiVA.org:uu-136483DiVA: diva2:377556
Available from: 2010-12-14 Created: 2010-12-13 Last updated: 2012-03-15Bibliographically approved

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Sharma, Hari Shanker
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