Delayed Granulocyte Colony-stimulating Factor Treatment Promotes Functional Recovery in Rats with Severe Contusive Spinal Cord Injury

Study Design: We used a severe contusive spinal cord injury (SCI) model and electrophysiologic, motor functional, immunohistochemical, and electron microscopic examinations to analyze the neuroprotective effects of delayed granulocyte colony-stimulating factor (G-CSF) treatment.

Objective: To determine the neuroprotective effects of delayed G-CSF treatment using multimodality evaluations after severe contusive SCI in rats.

Summary Of Background Data: Despite some reports that G-CSF treatment in the acute stage of different central nervous system injury models was neuroprotective, it has not been determined whether delayed G-CSF treatment can promote neural recovery in severe contusive SCI.

Methods: Rats with severe contusive SCI were divided into 2 groups: G-CSF group rats were given serial subcutaneous injections of G-CSF, and control group rats (controls) were given only saline injections on postcontusion days 9 to 13. Using the Basso-Beattie-Bresnahan scale and cortical somatosensory evoked potentials, we recorded functional evaluations weekly. The spinal cords were harvested for protein and immunohistochemical analysis, and for electron microscopy examination.

Results: The preserved spinal cord area was larger in G-CSF group rats than in control group rats. Both sensory and motor functions improved after G-CSF treatment. Detachment and disruption of the myelin sheets in the myelinated axons were significantly decreased, and axons sprouted and regenerated. There were fewer microglia and macrophages in the G-CSF group than in the control group. The levels of brain-derived neurotrophic factor were comparable between the 2 groups.

Conclusion: Delayed G-CSF treatment at the subacute stage of severe contusive SCI promoted spinal cord preservation and improved functional outcomes. The mechanism of G-CSF's protection may be related in part to attenuating the infiltration of microglia and macrophages.