The Role of CCL2 Chemoattractants in Lumber Myeloid Cell Trafficking and Locomotor Recovery Following Thoracic Spinal Cord Injury

Spinal cord injury (SCI) induces inflammation and damage across the cord that hinders neuronal plasticity and locomotor recovery. Previous studies of spinal cord response to injury show increased levels of chemoattractants (CCL2) and cell adhesion molecules (ICAM-1), chemotactic agents that induce the movement of specific cell types. Peripheral myeloid cells invade the lumbar region after thoracic SCI, rendering the lumbar microenvironment refractive to rehabilitation. We hypothesized that removal of CCL2 via genetic knockout (KO) will decrease myeloid cell infiltration into the lumbar spinal cord after SCI, to promote a more permissive microenvironment for rehabilitation interventions compared to typical, wild-type SCI (WT). We also hypothesized that downhill treadmill training 14-21 days post-injury would improve functional recovery in both KO and WT models. We used four groups with SCI at T9: CCL2KO exercised (n=8) or unexercised (n=8), and WT exercised (n=8) or unexercised (n=4). We quantified monocyte infiltration (IBA-1/p2ry12) and ICAM-1 expression via immunohistochemistry to identify co-regulatory features between chemoattractants and cell adhesion molecules in the trafficking of peripheral myeloid cells into the lumbar cord. Locomotion was assessed via Basso Mouse Scale (BMS) and 2D kinematics. Contrary to our hypothesis, the CCL2KO resulted in lower BMS scores than WT with and without training (untrained, p