SCF\u2009+\u2009G-CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus

Xuecheng Qiu,Lawrence Chin,Li-Ru Zhao,Suning Ping,Michele Kyle

doi:10.1186/s40478-021-01160-3

Abstract

Traumatic brain injury (TBI) is a major cause of long-term disability in young adults. An evidence-based treatment for TBI recovery, especially in the chronic phase, is not yet available. Using a severe TBI mouse model, we demonstrate that the neurorestorative efficacy of repeated treatments with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF + G-CSF) in the chronic phase is superior to SCF + G-CSF single treatment. SCF + G-CSF treatment initiated at 3 months post-TBI enhances contralesional corticospinal tract sprouting into the denervated side of the cervical spinal cord and re-balances the TBI-induced overgrown synapses in the hippocampus by enhancing microglial function of synaptic pruning. These neurorestorative changes are associated with SCF + G-CSF-improved somatosensory-motor function and spatial learning. In the chronic phase of TBI, severe TBI-caused microglial degeneration in the cortex and hippocampus is ameliorated by SCF + G-CSF treatment. These findings reveal the therapeutic potential and possible mechanism of SCF + G-CSF treatment in brain repair during the chronic phase of severe TBI.

Highlights

Traumatic brain injury (TBI) has become a public health crisis and a major cause of long-term disability and death among children and young adults in the United States [8, 71]
stem cell factor (SCF) + G‐CSF‐repeated treatments in the chronic phase of severe TBI improve neurological function To determine the neurorestorative efficacy of SCF + granulocyte colony-stimulat‐ ing factor (G-CSF) treatment in the chronic phase of severe TBI, spatial learning and memory were evaluated in a water maze test 3 weeks after the final repeated treatments (Fig. 1a)
TBI mice that received SCF + G-CSF-repeated treatments showed significant reductions in the latency to find the hidden platform as compared with TBI-vehicle controls on day 4 testing (Fig. 1b, p < 0.05). These findings suggest that SCF + G-CSF-repeated treatments in the chronic phase of severe TBI improve TBI-induced impairment of spatial learning and memory

Summary

Introduction

Traumatic brain injury (TBI) has become a public health crisis and a major cause of long-term disability and death among children and young adults in the United States [8, 71]. TBI has been recognized as a chronic medical condition [10, 45] which has long-term. Most permanent impairments have been found in severe TBI and some repeated mild TBI, even a single TBI can cause long-term neurodegeneration [10, 35]. Severe TBI increases the risk of developing depression, dementia, neurodegeneration, and even death during the chronic phase [24, 45]. Due to the improved medical and surgical management, the survival rate following severe TBI has dramatically increased [24].

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