Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase the expression of IGF‑1 after cardiac arrest in rats

Abstract

The present study aimed to investigate the beneficial effects and underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on global ischemic hypoxic brain injury. Cells collected from the femurs and tibias of male Sprague Dawley rats were used to generate BMSCs following three culture passages. A rate model of cardiac arrest (CA) was induced by asphyxia. One hour following return of spontaneous circulation (ROSC), BMSCs were transplanted through injection into the tail vein. Neurological status was assessed using modified neurological severity score (mNSS) tests 1, 3 and 7 days following ROSC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining were used to detect insulin-like growth factor 1 (IGF-1) expression in the hippocampus. Furthermore, double-fluorescent labeling of green fluorescent protein (GFP) and IGF-1 was used to detect the IGF-1 expression in transplanted BMSCs. Serum levels of protein S100-B were examined using ELISA. GFP-labeled BMSCs were observed in the hippocampus at 1, 3 and 7 days post transplantation through fluorescent microscopy. BMSC transplantation resulted in reduced protein S100-B levels. The mNSS of the BMSC-treatment group was significantly reduced compared with that of the CA group. The RT-qPCR analysis and immunohistochemistry results demonstrated that BMSC treatment significantly increased IGF-1 expression in the hippocampus. In addition, the double-fluorescent labeling results demonstrated that transplanted BMSCs expressed IGF-1 in the hippocampus. The results of the present study suggest that BMSC treatment promotes the recovery of cerebral function following CA in rats possibly through the secretion of IGF-1.

Intracerebroventricular Administration of hNSCs Improves Neurological Recovery after Cardiac Arrest in Rats

“…This early timing is consistent with a stroke model, in which rats receiving a hippocampal hNSC injection 24 h after middle cerebral artery occlusion (MCAO) showed an improvement in the foot-fault and adhesive removal tests administered 72 h later [32]. Stem cell therapy for global cerebral ischemia models involving 5-6 min of cardiac arrest, which leads to a mild brain injury, has been demonstrated beneficial at 3 days with adipose-derived stem cells [33] or bone marrow stem cells [34]. Intraventricular implantation of mesenchymal stem cells was reported to increase neurogenesis in the SVZ and the DG [35].…”

Optimizing Stem Cell Therapy after Ischemic Brain Injury

“…Compared with ischemic stroke, brain injury induced secondary to cardiac arrest has different conditions related to stem cell treatment (Table 2). 10,[16][17][18]51,[123][124][125][126][127] To date, BM-and AD-MSCs are the most commonly used stem cells in this pathology, and the cells are typically administered 1 to 2 hours after the return of spontaneous circulation. After 1 hour of brain ischemia, the subdural transplantation of iPSCs (1.0×10 6 ) is found to improve recovery in stroke rats.…”

“…Available preclinical studies indicate that IV doses ranging from 1×10 6 to 5×10 6 cells provide substantial behavioral gains in post-cardiac arrest rodents. 10,[16][17][18]51,[123][124][125] According to the allometric scaling approach from animals to humans recommended by the Food and Drug Administration, the equivalent MSC dose in humans is about 1.6×10 6 MSCs/kg. 9 The hMSC donor age is another critical factor affecting functional and structural outcomes in stroke affecting functional and structural outcomes in stroke.…”

“…Exogenous stem cell transplantation can improve the outcomes of patients with stroke [8][9][10][11][12][13][14][15] and hypoxic-ischemic brain injury induced by cardiac arrest. [16][17][18] Stem cell therapeutic benefits are not limited to their ability to replace diseased cells and tissues, but also extend to the provision of a supportive neurogenesis microenvironment over an extended period of time 19 through bioactive neurotrophic factor secretion, 20 mitochondrial transfer, 8,21 and exosome release. 7,[22][23][24][25] Transplanted stem cells can also be used as delivery vectors for agents such as chemotherapeutics, pro-drugs, and cytokines that can mediate inflammatory responses.…”

Bone marrow stromal cells improved functional recovery in spinal cord injury rats partly via the Toll‑like receptor‑4/nuclear factor‑κB signaling pathway

“…Recently, transplantation of bone marrow stromal cells (BMSCs) has emerged as a novel treatment for SCI (5)(6)(7). BMSCs are a population of heterogeneous mesenchymal cells located in the bone marrow that possess unlimited proliferative capacity and multidifferentiation properties (8,9). Furthermore, it has been reported that BMSCs have an important role in the immunomodulation of innate and adaptive immune processes in vitro and in vivo (10,11).…”