Introduction: This study investigated the specific mechanism of N-methyl-D-aspartate (NMDA) receptor-mediated spinal cord ischemia-reperfusion by comparing the protective effects of the voltage-gated Ca2+ channel blocker nimodipine and the NMDA receptor blocker K-1024 on the spinal cord.
Material and methods: In this study, 42 SD rats were divided randomly into four groups: non-blocking (n = 6), normal saline (n = 12), K-1024 (n = 12) and nimodipine (n = 12). The rats in three groups (saline, K-1024, nimodipine) received an intraperitoneal injection 30 minutes before ischemia. In these three groups, 6 out of 12 rats were selected randomly to have their thoracic aorta blocked with a balloon to induce spinal cord ischemia for 10 minutes. Then, the spinal cord tissues were collected. The remaining six rats were evaluated for nerve function at 1, 2, 4 and 8 hours after reperfusion. The lumbar spinal cord was removed for histological examination. The release of neurotransmitter amino acids was observed by high-pressure liquid chromatography, and the protein expression level of neuronal nitric oxide synthase (nNOS) in the spinal cord was determined by immunohistochemistry.
Results: All the animals in the normal saline group and five in the nimodipine group were paralysed after ischemia. Compared with the normal saline and nimodipine groups, the rats in the K-1024 group had more normal motor neurons and better behavioural scores. In addition, the histopathology of the rats in the K-1024 group was significantly better than in the normal saline and nimodipine groups. After 10 minutes of ischemia, there was no significant difference in glutamate concentration in each group. The protein expression level of nNOS in the K-1024 group was significantly downregulated compared with the saline and nimodipine groups. At 8 hours after reperfusion, the protein expression level of nNOS in the K-1024 group was significantly upregulated compared with the normal saline group.
Conclusions: The specific mechanism of the NMDA receptor blocker K-1024 in protection against spinal cord ischemia-reperfusion injury is related closely to the inhibition of NMDA receptors and the downregulation of the protein expression level of nNOS.
Keywords: K-1024; N-methyl-D-aspartate (NMDA) receptors; glutamate; neuronal nitric oxide synthase; spinal cord ischemia–reperfusion.