Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51. An experimental study using light and electron microscopy in the rat.
The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290/51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10-T11 segment under equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290/51 (50 mg/kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antioxidant compound H-290/51 attenuates cellularstress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using post-injury treatment with H-290/51 is needed to explore its therapeutic potentials in clinical settings.
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Division of Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Uppsala, Sweden. Sharma@surgsci.uu.se
H S
HS
Sharma
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Gordh
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Wiklund
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Mohanty
P O
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Sjöquist
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity / Q000187:drug effects; D019581:Neuropil / Q000187:drug effects / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D000975:Antioxidants; C088233:H290-51; D006360:Heat-Shock Proteins; D007211:Indoles