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02 May 2016 : Animal Research  

Intrathecally Transplanting Mesenchymal Stem Cells (MSCs) Activates ERK1/2 in Spinal Cords of Ischemia-Reperfusion Injury Rats and Improves Nerve Function

Yonghong WangABCDEF, He LiuCDF, Hong MaAG

DOI: 10.12659/MSM.896503

Med Sci Monit 2016; 22:1472-1479

Abstract

BACKGROUND: We investigated whether an intrathecal transplantation of mesenchymal stem cells (MSCs) activates extracellular adjusting protein kinase1 and 2(ERK1/2) in the spinal cords of rats following an ischemia-reperfusion injury, resulting in improved spinal cord function and inhibition of apoptosis.

MATERIAL AND METHODS: We observed the relationship between the activation of ERK1/2 in the rat spinal cord and intrathecal transplantation of MSCs, as well as the effect of U0126, a MEK1/2 (upstream protein of ERK1/2) inhibitor, on a spinal cord ischemia-reperfusion injury model in rats using Basso Beattie Bresnahan (BBB) scoring, somatosensory evoked potentials (SSEPs), immunohistochemistry, and Western blot analysis.

RESULTS: After transplantation of MSCs, the lower limb motor function score increased, and the incubation period of SSEPs and amplitude were improved. Moreover, following transplantation of MSCs, Bcl2 expression increased, whereas Bax expression decreased after reperfusion. Transplantation of MSCs significantly enhanced pERK1/2 expression in the spinal cord, as well as pERK1/2 in immunoreactive cells located in the grey matter of the L4/5 levels of the spinal cord, following ischemia reperfusion injury in rats. The effective dose of U0126 required to inhibit pERK1/2 expression was 200 µg/kg. Bcl-2 decreased and the level of Bax expression increased in the spinal cord after ischemia reperfusion injury, and the protective effects of MSCs were attenuated.

CONCLUSIONS: Our findings suggest that intrathecal transplantation of MSCs activates ERK1/2 in the spinal cord following ischemia reperfusion injury, partially improves spinal cord function, and inhibits apoptosis in rats.

Keywords: Cell Count, Animals, Cells, Cultured, Enzyme Activation, Evoked Potentials, Somatosensory, Extracellular Signal-Regulated MAP Kinases - metabolism, Extremities - physiopathology, Injections, Spinal, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells - cytology, Motor Activity, Neurons - pathology, Phosphorylation, Rats, Sprague-Dawley, Reperfusion Injury - therapy, Spinal Cord - physiopathology, Spinal Cord Injuries - therapy

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750