Neuroprotective effect of bone marrow mesenchymal stem cell transplantation on collagenase type Ⅶ induced cerebral hemorrhage rat model

Abstract

Objective To investigate the neuroprotective effect of bone marrow mesenchymal stem cell (BMMSC) transplantation on collagenase-induced intracerebral hemorrhage (ICH) adult sprague-Dawley (SD) rat model. Methods The collagenase-induced ICH models were constructed by injection of collagenase type Ⅶ into the striatum on the right side stereotaxically. Forty-five healthy male SD rats were selected and then randomly divided into 3 groups of fifteen each, control group, ICH rat model group (model group), BMMSC transplanted ICH group (transplantation group). In transplantation group, BMMSC were transplanted into the perilesional sites 2 h after ICH injury. Modified Neurological Severity Score (mNSS), brain-derived neurotrophic factor (BDNF) immunohistochemical expression, and TUNEL test (cell apoptosis) were assessed at the 1, 3, 7, 14 and 28 d after model-made/transplanted treatment of BMMSC. Results The mNSS score (P = 0.000) and apoptotic cell number (P = 0.000) of rats in different treatment groups at each observation time point showed statistically significant differences. Compared with the control group and the model group, the mNSS score of the transplantation group was lower 28 d after treatment (P < 0.05), showing a decreasing timeliness. The mNSS scores 7, 14 and 28 d after treatment was lower than that 1and 3 d after treatment (P < 0.05). On 1, 3, 7, 14 and 28 d after transplantation, the number of apoptotic cells in the model group and the transplantation group increased (P < 0.05) and reached the peak on 7 d after treatment (all P < 0.05). The number of apoptotic cells on 14 and 28 d was reduced but still higher than that on 1 and 3 d (all P < 0.05). In the transplantation group the expression of BDNF protein was significantly increased, and very few GFP + GFAP and GFP + NeuN positive cells were found in the brain tissue. These results indicated that the transplanted BMMSC had survived in the host brain tissue and with neuronal and glial differentiation. Conclusions Rat ICH model induced by collagenase type Ⅶ is stable for experimental study. The transplanted BMMSC can significantly provide better neuroprotection by increasing BDNF expression and reduce apoptosis. DOI:10.3969/j.issn.1672-6731.2019.09.007

Keywords

• cerebral hemorrhage
• bone marrow cells
• stem cell transplantation
• brain-derived neurotrophic factor
• apoptosis
• cells,cultured
• disease models,animal