Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis

Abstract

Background: Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.

Objective: To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.

Methods: We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.

Results: Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I² = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy.

Conclusion: Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

Keywords: Basso, Beattie, and Bresnahan scale score; granulocyte colony-stimulating factor; neurological function; optimal dosage; spinal cord injury.