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Neuroprotective effects of tramadol on cerebral injuries caused by hind limb ischaemia/reperfusion in rats

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Abstract

Skeletal muscle ischaemia–reperfusion-induced acute remote injury is mediated by activated neutrophils and formation of free radicals. Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischaemia. Tramadol hydrochloride is an effective analgesic used for severe acute and chronic pain conditions. The present study was designed to investigate the potential protective effects of tramadol hydrochloride on cerebral oxidative stress and damage as well as lipid peroxidation, brain oedema and histological changes induced by hind limb ischaemia and reperfusion injury in rats. Thirty-six male Wistar rats were randomly allocated into two experimental groups: ischaemia–reperfusion (group I) and ischaemia–reperfusion + tramadol hydrochloride (group II). Hind limb ischaemia was induced by clamping the femoral artery. After 2-h ischaemia, the clamp from the femoral vessels was removed and the animal underwent 24-h reperfusion. Tramadol hydrochloride was given intravenously at a dose of 20 mg/kg, immediately before reperfusion. After reperfusion, animals were euthanized and the cerebral structure, lipid peroxidation and brain oedema in the cerebral tissue were assessed. Histopathological assessment of cerebral injury was split into four grades. The extent of lipid peroxidation was measured by estimating the amount of malondialdehyde. Brain oedema was calculated as the percentage water content of the brain. Brain oxidative stress and damage were significantly attenuated by treatment with tramadol hydrochloride. Compared with the ischaemia–reperfusion group, histological changes in brain tissues (p < 0.006), lipid peroxidation (p < 0.004) and brain oedema (P < 0.002) were significantly decreased in the ischaemia reperfusion plus tramadol hydrochloride group. These findings suggest that tramadol hydrochloride is neuroprotective and alleviates cerebral injuries induced by hind limb ischaemia–reperfusion in rats.

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Correspondence to Mohammad Ashrafzadeh Takhtfooladi.

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Takhtfooladi, M.A., Jahanshahi, A., Sotoudeh, A. et al. Neuroprotective effects of tramadol on cerebral injuries caused by hind limb ischaemia/reperfusion in rats. Comp Clin Pathol 23, 1141–1146 (2014). https://doi.org/10.1007/s00580-013-1753-1

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