PLX5622 did not alter anxiety-like behaviour and showed limited microglial depletion efficacy in a spinal cord injury model in female rats

We previously reported that inflammation, when coupled with motor training following spinal cord injury (SCI) in female rats, promotes neuroplasticity as evidenced by enhanced performance in the trained task. However, this beneficial effect was accompanied by exacerbated anxiety-like behaviours, which are also a recognized consequence of SCI itself. Given that microglia are central mediators of the inflammatory response, their pharmacological ablation may help to clarify their specific role in enhanced motor recovery and their contribution to anxiety exacerbation. To this end, we first aimed to determine the efficacy and impact of the microglia-depleting compound PLX5622 in rats after SCI, as its effects in this traumatic injury model remain poorly characterized. The present study investigated how a four-week PLX5622 diet, started one week post-cervical SCI, influences anxiety-related behaviours, microglial depletion in the central nervous system (CNS), and SCI lesion pathology in adult female Lewis rats. Following the PLX5622 diet, no impact on anxiety-like behaviour was observed. The treatment achieved partial microglial depletion in all CNS regions examined, though to a lesser extent than reported in mice; no microglia morphological changes were detected in the brain or spinal cord. As expected due to delayed treatment, SCI lesion sizes were comparable across groups, but PLX5622-treated rats exhibited a less compact and thinner astrocytic scar at the lesion core. Importantly, our data revealed that PLX5622 also reduces resident macrophage populations in the liver, highlighting that its effects extend beyond the CNS. The limited impact of PLX5622 in our rat model of SCI, together with its lack of microglia specificity, raises concerns about its suitability for isolating microglial contributions to neuroplasticity, particularly regarding anxiety-like behaviour and post-injury motor recovery.