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

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.

Deletion of the Autism-Associated Protein SHANK3 Abolishes Structural Synaptic Plasticity after Brain Trauma

“…For example, a mild controlled cortical impact induced an increase in filopodia spines [ 38 ], and a moderate impact caused a decrease in filopodia and no alterations in the number of stubby spines [ 26 ]. With a more severe controlled cortical impact, mushroom and stubby spines diminished, and the filopodia number remained unchanged [ 39 ]. Hence, our results show that Shank3 deficiency abrogates the effects of mTBI observed in WT animals.…”

Chemically Functionalized Single-Walled Carbon Nanotubes Prevent the Reduction in Plasmalemmal Glutamate Transporter EAAT1 Expression in, and Increase the Release of Selected Cytokines from, Stretch-Injured Astrocytes in Vitro

“…It has also been suggested that G-CSF can enhance neurological function by promoting the sprouting of the corticospinal tract into the denervated side of the cervical spinal cord. Additionally, G-CSF may mitigate microglia degeneration and restore a proper balance in synaptic pruning within the hippocampus, leading to improved neurological outcomes [65]. Similarly, studies have shown that GM-CSF may also have significant protective properties in the chronic consequences of experimental TBI [66,67].…”