Combined Neuroprotective Effects of N,N‐Dimethyltryptamine and Ventral Root Reimplantation Following Spinal Root Avulsion in Rats
Paola Andrea Caro Aponte, Edison Huertas Montoya, Ítalo Odone Mazali, Alessandra Sussulini, Benedito Barraviera, Rui Seabra Ferreira, Luciana Politti Cartarozzi, Alexandre Leite Rodrigues de Oliveira
Journal of Neurochemistry January 29, 2026 DOI: 10.1111/jnc.70364 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult female Lewis rats |
| Interventions | DMT Ventral root reimplantation Fibrin sealant biopolymer |
| Dose | 1, 2.5, or 5 mg/kg i.p. daily for 2 weeks; optimal dose identified as 1 mg/kg |
| Duration | 2-week treatment, 2-week post-injury evaluation |
| Measures | neuronal survival, glial reactivity, synaptic preservation, gene expression of GDNF, FGF-2, VGF-A, Bcl-2, Bcl-XL |
| Topics | 5-MeO-DMT DMT |
| Keywords | Neuroprotection Axotomy Neurotrophic factors Neurotrophin Avulsion Anesthesia Pharmacology Therapeutic effect Pathophysiology Downregulation and upregulation Brain-derived neurotrophic factor Axon Spinal cord Surgery |
| Key findings | DMT at 1 mg/kg combined with surgical root reimplantation and fibrin sealant biopolymer significantly enhanced motor neuron survival, reduced glial reactivity, and upregulated GDNF expression after ventral root avulsion. |
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.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |
Citations in the library
Cites 15
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
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- The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization. Frontiers in Pharmacology March 2, 2016
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One 2014
and 10 more in the library