Tumor necrosis factor-a antagonist reduces apoptosis of neurons and oligodendroglia in acute spinal cord injury
Hideaki Nakajima Department of Orthopaedics and Rehabilitation Medicine
Faculty of Medical Sciences, University of Fukui
Eiheiji, Fukui 910-1193, Japan
Abstract:
Objectives:
To elucidate the contribution of etanercept to the pathological cascade in spinal cord injury and its possible suppression of neuronal and oligodendroglial apoptosis.
Methods:
Etanercept or saline (control) was administered by intraperitoneal injection 1 hour after thoracic spinal cord injury in rats. The expressions and localizations of TNF-α, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2) were examined by immunoblot and immunohistochemical analyses. HE and LFB staining, BBB scale, the number of TUNEL-positive cells, and the immunoreactivity to active caspase-3 and caspase-8 were examined.
Results:
Immunoblot and double immunofluorescence staining revealed suppression of TNF-α, TNFR1, and TNFR2 expression after administration of etanercept in the acute phase. LFB staining demonstrated potential myelination in the etanercept-treated group, together with an increased BBB locomotor score. Double immunofluorescence staining showed a significant decrease in TUNEL-positive neurons and oligodendroglia after etanercept administration. Immunoblot analysis demonstrated overexpression of activated caspase-3 and caspase-8 after spinal cord injury, which was markedly inhibited by etanercept.
Conclusion:
TNF-α antagonist, etanercept, could be clinically used to reduce spinal cord tissue damage following traumatic insult, possibly through inhibition of the TNF-α/TNFR pathway and TNF-α-induced apoptosis in neurons and oligodendroglia.
