N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.
Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection.
Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
Qiang
Q
Zhang
Department of Neurology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Yang
Y
Shao
Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
Changsong
C
Zhao
Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
Juan
J
Cai
Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
Sheng
S
Sun
MK-801; apoptosis; fetal spinal cord; graft; spinal cord injury