Stem cell factor and granulocyte colony-stimulating factor enhance neural repair in the chronic phase of severe traumatic brain injury

The long-term impact of severe traumatic brain injury on cognitive and motor functions has emerged as a pressing public health issue across the United States. Currently, no therapy exists to enhance recovery in the chronic phase of severe traumatic brain injury. This study aims to determine the efficacy of a combined treatment of stem cell factor and granulocyte colony-stimulating factor in improving recovery during the chronic stage of traumatic brain injury. Mice at young adult age were subjected to severe traumatic brain injury in the right hemisphere, followed by subcutaneous administration of the two growth factors for seven days, beginning six months post-injury. Behavioral assessments were conducted at four weeks post-treatment. Two weeks before euthanasia, biotinylated dextran amines were injected into the contralateral somatosensory motor cortex. We observed that the treatment during the chronic phase of severe traumatic brain injury reduced persistent impairments in locomotor and somatosensory-motor function. Additionally, this intervention led to improvements in spatial learning ability, which was significantly impaired following severe traumatic brain injury. Neurostructural assessments showed that the intervention reversed traumatic brain injury-induced damage to dendrites and axons in the affected cortical and hippocampal regions. Moreover, the treatment increased pre-synaptic puncta on the ipsilesional cortical side and promoted the crossing of biotinylated dextran amines-traced corticospinal tract fibers into the denervated cervical spinal cord. These data suggest that stem cell factor + granulocyte colony-stimulating factor may serve as an effective strategy to promote brain repair in chronic severe traumatic brain injury.