Preconditioned MSCs Alleviate Cerebral Ischemia-Reperfusion Injury in Rats by Improving the Neurological Function and the Inhibition of Apoptosis

Abstract

Mesenchymal stem cells (MSCs) have great application prospects in the treatment of ischemic injury. However, their long-time cultivation before transplantation and poor survival after transplantation greatly limit the therapeutic effect and applications. This study aimed to investigate whether MSCs under the ischemic microenvironment could improve their survival and better alleviate cerebral ischemic injury. Firstly, we used ischemic brain tissue to culture MSCs and evaluated the functional changes of MSCs. Then a middle cerebral artery occlusion (MCAO) model was induced in rats, and the pretreated MSCs were injected via the tail vein. The adhesive removal test, rotarod test, modified neurological severity score, and pathological analyses were applied to assess the rats’ neurological function. Then the expression of neuron and apoptosis related markers was detected. The results indicated that ischemic brain tissue pretreated MSCs promoted the proliferation and the release of the growth factors of MSCs. Meanwhile, in MCAO model rats, transplantation of pretreated MSCs enhanced the neurogenesis, attenuated behavioral changes, reduced infarct size, and inhibited apoptosis. The expression of B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), NF-L, and NeuN were increased, while BCL2-Associated X (Bax) and Caspase-3 decreased. Our results suggest that MSCs pretreatment with stroke brain tissue could be an effective strategy in treating cerebral ischemic injury.

Keywords

• mesenchymal stem cells
• neurological function
• ischemia and reperfusion
• ischemic microenvironment
• apoptosis