LAUSR

The inflammatory response associated with traumatic spinal cord injury (SCI) contributes to locomotor and sensory impairments. Pro-inflammatory (M1) macrophages/microglia (MφMG) are the major cellular players in this response as they promote chronic inflammation resulting in injury expansion and tissue damage. Fatty Acid-Binding Protein 4 (FABP4) promotes M1 MφMG differentiation; however, it is unknown if FABP4 also plays a role in the etiology of SCI. The present study investigates whether FABP4's gene expression influences functional recovery following SCI. Analysis of qPCR data shows a robust induction of FABP4 mRNA (>100 fold) in rats subjected to a T9-T10 contusion injury compared to control. Western blot experiments reveal significant upregulation of FABP4 protein at the injury epicenter, and immunofluorescence analysis identifies this upregulation occurs in CD11b+ MφMG. Furthermore, upregulation of FABP4 gene expression correlates with PPARγ downregulation, inactivation of Iκβα, and the activation of the NF-κB pathway. Analysis of locomotor recovery using the Basso-Beattie-Bresnahan's (BBB) locomotor scale and the CatWalk gait analysis system shows that injured rats treated with FABP4 inhibitor BMS309403 have significant improvements in locomotion compared to vehicle controls. Additionally, inhibitor-treated rats exhibit enhanced autonomic bladder reflex recovery. Immunofluorescence experiments also show the administration of the FABP4 inhibitor increases the number of CD163+ and Liver Arginase+ M2 MφMG within the epicenter and penumbra of the injured spinal cord 28 dpi. These findings show that FABP4 may significantly exacerbate locomotor and sensory impairments during SCI by modulating macrophage/microglial activity.