The TSPO Ligand 2-Cl-MGV-1 Regulates Neurogenesis and Promotes Neural Recovery Following Traumatic Brain Injury

We evaluated the effects of the TSPO ligand 2-Cl-MGV-1 on neurogenesis in a murine model with traumatic brain injury (TBI). Mice treated with 7.5 mg/kg of 2-Cl-MGV-1 for 60 days post-TBI showed reduced neuroinflammation and neurodegeneration in the cortex and hippocampus, as indicated by decreased TSPO expression. Notably, 2-Cl-MGV-1 modulated neurogenesis in a niche-specific manner. In the subventricular zone (SVZ), it enhanced neurogenic activity by increasing the expression of neural stem (Nestin) and progenitor (NeuroD1) cell markers, and by redirecting migration of neuroblasts from their canonical path to the olfactory bulb toward the injured cortex. This shift suggests an adaptive reparative response that facilitates brain recovery. In contrast, hippocampal neurogenesis was not enhanced; expression of Nestin, NeuroD1, and β-III-Tubulin in the dentate gyrus was reduced by 2-Cl-MGV-1. Nonetheless, hippocampal neuroprotection was observed, likely due to anti-inflammatory and anti-neurodegenerative effects of the treatment. These results reveal a niche-specific modulation of neurogenesis by 2-Cl-MGV-1, promoting regenerative activity by the ventricular neurogenesis while pre-serving hippocampal integrity through non-neurogenic mechanisms. Altogether, our findings support the therapeutic potential of 2-Cl-MGV-1 to improve brain recovery after TBI by reducing chronic responses post-injury and enhancing endogenous repair mecha-nisms in a neurogenic niche-specific manner.