ISSN: 2474-9214
Authors: Ahmad Reza Dehpour
Background: This study addresses gaps in understanding the impact of nicotine on neuroinflammation, specifically in the context of secondary spinal cord injury (SCI). Uncertainties persist regarding the cellular and molecular components influenced by nicotine and whether its effects during the chronic phase of SCI are receptor-mediated. The research systematically investigates these aspects, aiming to provide insights into the nuanced mechanisms underlying nicotine’s impact on neuroinflammation in SCI. Methods: Male rats underwent either a sham operation or spinal cord injury (SCI). The study employed four nicotine groups and two methyllycaconitine (MLA) groups as treatment cohorts. Subsequent to behavioral assessments including locomotion impairment and mechanical allodynia, the optimal nicotine dosage was selected for comprehensive cellular and molecular evaluations of neuroinflammation in chronic phase of secondary SCI. Results: The administration of nicotine at a pre-treatment dosage of 1mg/kg demonstrated a mitigating effect on neuroinflammation, evidenced by improvements at both cellular and molecular levels. This intervention led to enhanced spinal cord tissue integrity, decreased M1/M2 polarization, and modulation of pro-inflammatory markers (NF-κB, TNF-α, IL-1β, IL-6), coupled with an increase in anti-inflammatory cytokine IL-10. Notably, these effects were negated upon the α7- nAChR, underscoring the receptor-dependent nature of nicotine’s impact. Conclusion: Pre-treatment with nicotine improved behavioral impairment of SCI possibly through alleviating neuroinflammation by changing macrophage phenotyping and cytokine levels. These effects were mediated by α7 nAChR.
Keywords: (Apha-7) Nicotinic Acetylcholine Receptor (Α7 Nachr); Macrophage Polarization; Neuroinflammation; Nicotine; Spinal Cord Injury (SCI)
