Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury

Laboratory investigation

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Object

A glial scar is thought to be responsible for halting neuroregeneration following spinal cord injury (SCI). However, little quantitative evidence has been provided to show the relationship of a glial scar and axonal regrowth after injury.

Methods

In this study performed in rats and dogs, a traumatic SCI model was made using a weight-drop injury device, and tissue sections were stained with H & E for immunohistochemical analysis. The function and behavior of model animals were tested using electrophysiological recording and the Basso-Beattie-Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord after SCI in dogs was observed using MR imaging.

Results

The morphological results showed that the formation of an astroglial scar was defined at 4 weeks after SCI. While regenerative axons reached the vicinity of the lesion site, the glial scar blocked the extension of regrown axons. In agreement with these findings, the electrophysiological, behavioral, and in vivo MR imaging tests showed that functional recovery reached a plateau at 4 weeks after SCI. The thickness of the glial scars in the injured rat spinal cords was also measured. The mean thickness of the glial scar rostral and caudal to the lesion cavity was 107.00 ± 20.12 μm; laterally it was 69.92 ± 15.12 μm.

Conclusions

These results provide comprehensive evidence indicating that the formation of a glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals a critical time window of postinjury recovery and a detailed spatial orientation of glial scar, which would provide an important basis for the development of therapeutic strategy for glial scar ablation.

Abbreviations used in this paper: ABC = avidin-biotin peroxidase complex; BBB = Basso-Beattie-Bresnahan; BDA = biotin dextran amine; DAB = 3, 3′-diaminobenzidine; GFAP = glial fibrillary acidic protein; MEP = motor evoked potential; NF-200 = neurofilament-200; PBS = phosphate-buffered saline; SCI = spinal cord injury; SSEP = somatosensory evoked potential.
Article Information

Contributor Notes

Address correspondence to: Hua Feng, M.D., Ph.D., Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. email: fenghua8888@yahoo.com.cn.* Drs. Hu and Zhou contributed equally to this work.

© AANS, except where prohibited by US copyright law.

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