Microglia-mediated neuroinflammation constitutes a pivotal secondary injury mechanism after traumatic brain injury (TBI). Recent studies have unveiled the role of Nr1d1 in neuroinflammation and glial activation in the Central Nervous System (CNS) injury, found the activation of Nr1d1 appears to prevent inflammation and apoptosis cell death. However, the role of Nr1d1 in the regulation of M1/M2 polarization and neuroinflammatory responses in TBI remains unclear. The purpose of this study is to investigate the effects of Nr1d1 on neuroinflammatory responses in the acute phase of TBI. SR9009 (100 mg/kg) was administered by intraperitoneal injection to activate Nr1d1. Neurological impairments were assessed using the modified neurological severity score (mNSS). Molecular levels were evaluated through Western Blotting and quantitative real-time polymerase chain reaction. Measurement of the water content of brain tissue was used to assess cerebral edema, and the damaged area of brain tissue was evaluated by Hematoxylin-Eosin (H&E) staining. The functional behavioral assessment was used to evaluate the cognitive impairments and emotional change. Our study, for the first time, demonstrates that the circadian rhythm of Nr1d1 is disrupted during the acute phase of TBI. We also found Nr1d1 prevented nerve dysfunction and contributed to the recovery of neurological impairment, promoted the transformation of microglia phenotype, and reduced the damage to neurons, synaptic structures, and the neuroinflammation. These findings unveiled that Nr1d1 may represent a promising therapeutic target for the successful treatment of TBI and for improving neurological deficits during the acute phase of TBI.
Li et al. (Wed,) studied this question.