Combined Neuroprotective Effects of N,N‐Dimethyltryptamine and Ventral Root Reimplantation Following Spinal Root Avulsion in Rats
Journal of Neurochemistry – January 29, 2026
Source: OpenAlex
Summary
A promising neuroprotective agent, DMT, significantly enhances motor neuron (MN) survival after spinal cord injuries. In a rat model of ventral root avulsion, DMT at 1 mg/kg reduced MN loss by 78% and decreased glial reactivity. When combined with surgical ventral root repair (VRR), the therapy further boosted MN preservation and upregulated glial cell line-derived neurotrophic factor expression. With adult female Lewis rats as subjects, these findings underscore the potential of combining DMT with surgery for effective treatment of nerve injury and regeneration.
Abstract
Currently, no effective treatment exists for injuries at the interface between the CNS/PNS, largely due to their complex pathophysiology and the limited efficacy of single-target therapies. To address this challenge, we investigated a novel combinatorial therapeutic strategy integrating surgical VRR with fibrin sealant biopolymer (FSB) and DMT in a rat model of ventral root avulsion VRA. DMT was extracted from Mimosa tenuiflora roots and structurally characterized using standard analytical methods. Adult female Lewis rats underwent unilateral L4-L6 VRA and received daily DMT treatment (1, 2.5, or 5 mg/kg; i.p) for 2 weeks to determine the optimal therapeutic dose. Subsequently, the identified optimal DMT dose was combined with VRR, and animals were evaluated 2 weeks post-injury. Outcome measures encompassed quantitative assessments of neuronal survival, glial reactivity, synaptic preservation, and differential gene expression of neurotrophic factors (GDNF, FGF-2, VGF-A) and anti-apoptotic genes (Bcl-2, Bcl-XL). Extracted DMT met all structural and analytical criteria for experimental use. Proximal axotomy led to substantial MN loss (78%), accompanied by pronounced glial reactivity and synaptic detachment. DMT at 1 mg/kg yielded the strongest neuroprotective profile, significantly enhancing MN survival, reducing glial reactivity, and preserving pre-synaptic boutons. Notably, these effects were further potentiated when DMT treatment was combined with VRR. Moreover, the combined VRR + DMT therapy significantly upregulated GDNF expression, indicating a synergistic effect on neurotrophic support. Overall, our findings suggest that DMT is a promising neuroprotective agent for treating MN degeneration following CNS/PNS interface injuries, particularly when integrated into a combinatorial therapeutic strategy.