Neuroprotection and immunomodulation after treatment with NeuroBoost and NeuroHeal following ventral root crush in mice.

Pharmacological immunomodulation can prevent neuronal loss and reactive gliosis after injuries to spinal nerve roots. NeuroBoost (NB) and NeuroHeal (NH) were used to compare their effects on neuronal survival, glial and immune response, and functional recovery after root injury in mice. Our data showed that the NB combination presented a significant difference in the survival of motoneurons after injury compared to the vehicle group (0.71 ± 0.07 vs. 0.60 ± 0.01, p = 0.04, ratio ipsi/contralateral), decreased astrogliosis and microglia reactivity (astrogliosis: 7 dpi: VE vs. NB 4.4 ± 1.06 vs. 3.08 ± 0.39, p = 0.007; 28 dpi: VE vs. NB 5.02 ± 1.06 vs. 1.82 ± 0.53, p = 0.0003; microglial reactivity: 28 dpi: VE vs. NB 3.95 ± 0.88 vs. 2.63 ± 0.37, p = 0.02; integrated density of pixels - ratio ipsi/contralateral). A shift to a non-reactive profile was observed and functionally, the NB combination brought gains in gait recovery. In relation to treatment with NH, we observed that the combination showed a significant difference in neuronal survival at 7 days of treatment (0.76 ± 0.05 vs. 0.62 ± 0.10, p = 0.04) compared to the vehicle group. Also, a decrease in astrogliosis (7 dpi: VE vs. NH 4.4 ± 1.06 vs. 3.04 ± 0.83, p = 0.031; 28 dpi: VE vs. NH 5.02 ± 1.06 vs. 2.27 ± 0.45, p = 0.0007), and an increase in the M1 macrophages was observed after 14 days of treatment (VE: 45.26 vs. NH: 71.23 ± 18.36, p = 0.01). The functional recovery results were similar to the NB combination. Overall, both combinations showed significant benefits after root injury in mice, pointing to the possibility of clinical translation.