Traumatic spinal cord injury refers to the direct or indirect external force on the spinal cord, resulting in damage to the structure and function of the spinal cord. The elderly are prone to falls, which increases the probability of spinal cord injury, which will lead to permanent deficits in sensory and motor functions. Currently, there is no clinical curative treatment. There are also literatures showing that spinal cord injury is characterized by acute mechanical injury, which leads to blood vessel rupture, and the growth of new blood vessels is a nutrient that promotes the repair of spinal cord injury. However, whether aging has an impact on angiogenesis after spinal cord injury is unclear.

Recently, a study by Xiangya Hospital of Central South University in China found that metformin can accelerate the growth of blood vessels in aged mice with spinal cord injury, and promote the recovery of nerve function and tissue repair. The findings were published in Neural Regeneration Research.

Metformin has been used since the 1960s to treat type 2 diabetes and metabolic syndrome. Recently, more and more studies have shown that metformin has beneficial effects on cancer and polycystic ovary syndrome, and it has also been reported that metformin has a protective effect on the heart. However, it remains unclear whether metformin accelerates blood vessel growth and thereby restores neurological function in aged mice with spinal cord injury.

In this study, in order to explore the differences between young and old mice, the researchers selected 2-month-old and 18-month-old mice as experimental subjects, induced the mice to become spinal cord injury model mice, and then induced the spinal cord injury model mice Aged mice were intraperitoneally injected with metformin, and the control group was supplemented with PBS (phosphate buffered saline). Neurological evaluations such as motor function and sensory function were performed by the Basso Mouse Scale (BMS) and the von Frey filament test.

The results showed that there was no significant difference in BMS scores between healthy young mice and aged mice, but compared with young mice after spinal cord injury, aged mice with spinal cord injury had significantly lower BMS scores and a better response to pain. High withdrawal threshold (insensitivity to pain). This suggests that aging delays functional recovery in mice with spinal cord injuries.

The researchers also found that older spinal cord-injured mice had a larger area of diseased tissue and less healthy spinal cord tissue around the injury site compared with younger spinal cord-injured mice. Footprint analysis revealed that aged spinal cord-injured mice exhibited severely impaired strides and paws. These findings suggest that aged mice have worse spinal cord pathology and more impaired neurological function than young mice with spinal cord injury.

Subsequently, the researchers found that after 56 days after spinal cord injury, the spinal cord vascular parameters of aged mice were significantly lower than those of young mice. This suggests that impaired neurological recovery in aged SCI mice is associated with impaired vascular regeneration.

Aging reduces number of blood vessels in mice with spinal cord injury

To assess the effect of metformin on neurological recovery and tissue repair after spinal cord injury in aged mice, the researchers assessed the recovery of hindlimb motor function. The results showed that aged mice supplemented with metformin had higher BMS scores and significantly improved motor function relative to controls. Furthermore, aged mice with spinal cord injury supplemented with metformin had lower withdrawal thresholds to pain than controls. This suggests that metformin promotes sensory recovery in aged mice with damaged spinal cords. At the same time, the researchers found that compared with the control group, the area of damaged tissue in the metformin group was significantly reduced, and the area of normal spinal cord tissue in the injured site was significantly increased. Footprint analysis revealed that metformin caused older mice with spinal cord damage to take longer strides and less paw rotation than controls. These results suggest that metformin is neuroprotective and can significantly improve tissue repair and neurological recovery in aged mice after spinal cord injury.

Metformin promotes neurological recovery and tissue repair after spinal cord injury in aged mice

The researchers found that metformin can significantly increase the ratio of CD31 (platelet-endothelial cell adhesion molecule) positive cells in the injury site of aged mice after spinal cord injury. This suggests that metformin promotes blood vessel regeneration in aged mice with spinal cord injury.

The researchers speculate that "the neuroprotective effect of metformin after spinal cord injury in aged mice may be due to its promotion of angiogenesis." a new treatment method.

references：

1. Zhao, Jin-Yun1,2,3,4; Sheng, Xiao-Long1,2,3,4; Li, Cheng-Jun1,2,3,4; Qin, Tian1,2,3,4; He, Run-Dong1,2,3,4; Dai, Guo-Yu1,2,3,4; Cao, Yong1,2,3,4; Lu, Hong-Bin2,3,4,5; Duan, Chun-Yue1,2,3,4,*; Hu, Jian-Zhong1,2,3,4,*. Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway. Neural Regeneration Research 18(7):p 1553-1562, July 2023. | DOI: 10.4103/1673-5374.360245.