• Jenniffer Licero Campbell, Miguel Serrano-Illàn, Magda Descorbeth, Kathia Cordero, Johnny D Figueroa, and Marino De León.
• Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.
• J. Neurotrauma. 2022 Aug 1; 39 (15-16): 109911121099-1112.

AbstractThe 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 quantitative polymerase chain reaction data shows a robust induction of FABP4 messenger RNA (mRNA; >100 fold) in rats subjected to a T9-T10 contusion injury compared with control. Western blot experiments reveal significant upregulation of FABP4 protein at the injury epicenter, and immunofluorescence analysis identifies that this upregulation occurs in CD11b+ MϕMG. Further, upregulation of FABP4 gene expression correlates with peroxisome proliferator-activated receptor γ (PPARγ) downregulation, inactivation of Iκβα, and the activation of the NF-κB pathway. Analysis of locomotor recovery using the Basso-Beattie-Bresnahan's locomotor scale and the CatWalk gait analysis system shows that injured rats treated with FABP4 inhibitor BMS309403 have significant improvements in locomotion compared with 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 days post-injury. These findings show that FABP4 may significantly exacerbate locomotor and sensory impairments during SCI by modulating macrophage/microglial activity.

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