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Restoration of Intracortical and Thalamocortical Circuits After Transplantation of Bone Marrow Mesenchymal Stem Cells Into the Ischemic Brain of Mice *

Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides a promising regenerative medicine for stroke. Whether BMSC therapy could repair ischemia-damaged neuronal circuits and recover electrophysiological activity has largely been unknown. To address this issue, BMSCs were implanted into the ischemic barrel cortex of adult mice 1 and 7 days after focal barrel cortex stroke. Two days after the first transplantation (3 days after stroke), the infarct volume determined by TTC staining was significantly smaller in BMSC-treated compared to vehicle-treated stroke mice. The behavioral corner test showed better long-term recovery of sensorimotor function in BMSC-treated mice. Six weeks poststroke, thalamocortical slices were prepared and neuronal circuit activity in the peri-infarct region of the barrel cortex was determined by extracellular recordings of evoked field potentials. In BMSC-transplanted brain slices, the ischemia-disrupted intracortical activity from layer 4 to layer 2/3 was noticeably recovered, and the thalamocortical circuit connection was also partially restored. In contrast, much less and slower recovery was seen in control animals of barrel cortex stroke. Immunohistochemical staining disclosed that the density of neurons, axons, and blood vessels in the peri-infarct region was significantly higher in BMSC-treated mice, accompanied with enhanced local blood flow recovery. Western blotting showed that BMSC treatment increased the expression of stromal cell-derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) in the peri-infarct region. Moreover, the expression of the axonal growth associated protein-43 (GAP-43) was markedly increased, whereas the axonal growth inhibiting proteins ROCK II and NG2 were suppressed in the BMSC-treated brains. BMSC transplantation also promoted directional migration and survival of doublecortin (DCX)-positive neuroblasts in the peri-infarct region. The present investigation thus provides novel evidence that BMSC transplantation has the potential to repair the ischemia-damaged neural networks and restore lost neuronal connections. The recovered circuit activity likely contributes to the improved sensorimotor function after focal ischemic stroke and BMSC transplantation.

* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 11-03-2017
Authors: Song, Mingke; Mohamad, Osama; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping
Source: Cell Transplantation, Volume 22, Number 11