Anti-chronic stress effect of bone marrow mesenchymal stem cell transplantation in rats with spinal cord injury

Abstract

Objective To investigate the anti-chronic stress effect of bone marrow mesenchymal stem cell (BMSCs) transplantation in rats with spinal cord injury. Methods Forty-eight adult SD rats were divided into control group, model group and treatment group according to the random number table, with 16 rats each. In model and treatment groups, lower thoracic (T10) spinal cord injury were constructed using the modified Allen's method. In control group, only laminectomy was performed. After 7 days, 100 μl Hank's buffer suspension containing 1.0×106 BMSCs was injected into the subarachnoid space of L4-5 intervertebral space of rats in control group and treatment group. While in model group, only the equal volume of Hank's buffer was used. Basso-Beattie-Bresnahan (BBB) scale was performed to evaluate hindlimb motor function in rats. At postoperative 14 and 28 days, blood samples were collected to measure adrenocorticotropic hormone (ACTH), norepinephrine (NE), epinephrine (E) and corticosterone (CORT) using the ELISA method; brains were harvested for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor proteins GluR1 and GluR2 immunohistochemical staining. Results After injury, BBB scores in model and treatment groups were similar, but both were lower than that in control group (P<0.05). After BMSCs transplantation, BBB score in treatment group [21 d: (9.85±0.82)points and 28 d: (11.23±0.68)points] improved continuously compared to model group [21 d: (8.42±0.39)points and 28 d: (8.84±0.25)points], but all were lower than that in control group [(21.00±0.00)points, P<0.05]. ACTH contents in model and treatment groups at 14 d [(104.80±6.16) and (98.50±4.07)pg/ml] and 28 d [(101.40±2.33) and (96.50±2.28)pg/ml] were higher than those in control group [(90.40±11.36) and (83.20±5.22)pg/ml] (P<0.05). CORT contents in model and treatment groups [(44.40±1.44) and (43.30±1.17)ng/ml] was lower than that in control group [(48.20±2.27)ng/ml] at 14 d, but were found to be elevated [(70.40±1.90) and (61.40±1.83)ng/ml] compared to control group [(46.40±1.49)ng/ml] at 28 d (P<0.05). Meanwhile, the CORT content in treatment group was lower than that in model group (P<0.05). Changes in NE and E contents among the groups were similar with ACTH. Immunohistochemical staining suggested the amounts of GluR1 and GluR2 positive cells in treatment group lowered compared to control group (P<0.05), but increased in model group compared to control group (P<0.05). Conclusion BMSCs transplantation can improve the hindlimb motor function, contribute to reducing the secretion of stress-related hormones ACTH, CORT, NE and E, and down-regulate the expression of AMPA receptor proteins GluR1 and GluR2 in rats with spinal cord injury, suggesting a potential role in anti-chronic stress. Key words: Spinal cord injuries; Mesenchymal stem cell transplantation; Stress