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Vahid Alivirdiloo1 
, Mobasher Hajiabbasi2 , Ali Siahposht Khachaki *3 , Aydin Sadeghi4 , Saeid Bagheri-Mohammadi5
, Mobasher Hajiabbasi2 , Ali Siahposht Khachaki *3 , Aydin Sadeghi4 , Saeid Bagheri-Mohammadi5
1- Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.
2- Islamic Azad University of Tonekabon, Tonekabon, Iran.
3- Immunogenetics Research Center, Departments of Physiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
4- Amol Campus of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
5- Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran. & Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
2- Islamic Azad University of Tonekabon, Tonekabon, Iran.
3- Immunogenetics Research Center, Departments of Physiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
4- Amol Campus of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
5- Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran. & Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract:
Objective: To test whether nobiletin (NOB) improves neurological and motor function and mitigates secondary injury (edema, BBB disruption, histopathology) via modulation of IL‑1β and IL‑10 in a severe diffuse TBI rat model.
Methods: Adult male Wistar rats (n=56; 7 groups, 8-10 rats/group) underwent Marmarou weight‑drop TBI or sham/controls: Intact, Sham, TBI, Vehicle/Saline, NOB 25 mg/kg, NOB 50 mg/kg, NOB 100 mg/kg. NOB or vehicle was administered intraperitoneally 30 min post‑injury (single dose; [insert solvent and volume]). Neurological (VCS) and motor (beam walk, balance beam) scores were assessed on Days 0–3 by blinded evaluators. Brain water content and Evans blue extravasation were measured at 72 h. CSF IL‑1β and IL‑10 were quantified by ELISA. Histology (H&E, 5 µm) was evaluated blinded; [optional] semi‑quantitative neuronal injury scores were assigned. Primary analysis for longitudinal behavior used two‑way repeated‑measures ANOVA; other endpoints used one‑way ANOVA with Tukey’s test; data are mean ± SEM.
Results: Compared with TBI/Vehicle, NOB 25 and 50 mg/kg improved VCS and motor performance across Days 1–3 (Group×Day interaction [insert F, p]). AUC analyses corroborated these effects. NOB 50 mg/kg most consistently reduced brain water content ([insert % reduction] vs TBI; p=[insert]) and Evans blue permeability ([insert % reduction]; p=[insert]). CSF IL‑1β increased after TBI and was reduced by NOB 25 and 50 mg/kg ([insert values], p=[insert]); IL‑10 decreased after TBI and was increased by NOB 25 and 50 mg/kg ([insert], p=[insert]). The 100 mg/kg dose showed limited or no benefit across endpoints. Histology revealed attenuated neuronal edema/pyknosis and vascular congestion with NOB 25–50 mg/kg; [if scored] injury scores were reduced vs TBI/Vehicle (p=[insert]).
Conclusion: A single post‑injury dose of nobiletin at 25–50 mg/kg improved neurological outcomes and mitigated edema, BBB disruption, histopathology, and cytokine imbalance within 72 h after severe diffuse TBI, with 50 mg/kg showing the most consistent efficacy. The 100 mg/kg dose was not beneficial. Findings support anti‑inflammatory and vasculoprotective actions of nobiletin in acute TBI.
Methods: Adult male Wistar rats (n=56; 7 groups, 8-10 rats/group) underwent Marmarou weight‑drop TBI or sham/controls: Intact, Sham, TBI, Vehicle/Saline, NOB 25 mg/kg, NOB 50 mg/kg, NOB 100 mg/kg. NOB or vehicle was administered intraperitoneally 30 min post‑injury (single dose; [insert solvent and volume]). Neurological (VCS) and motor (beam walk, balance beam) scores were assessed on Days 0–3 by blinded evaluators. Brain water content and Evans blue extravasation were measured at 72 h. CSF IL‑1β and IL‑10 were quantified by ELISA. Histology (H&E, 5 µm) was evaluated blinded; [optional] semi‑quantitative neuronal injury scores were assigned. Primary analysis for longitudinal behavior used two‑way repeated‑measures ANOVA; other endpoints used one‑way ANOVA with Tukey’s test; data are mean ± SEM.
Results: Compared with TBI/Vehicle, NOB 25 and 50 mg/kg improved VCS and motor performance across Days 1–3 (Group×Day interaction [insert F, p]). AUC analyses corroborated these effects. NOB 50 mg/kg most consistently reduced brain water content ([insert % reduction] vs TBI; p=[insert]) and Evans blue permeability ([insert % reduction]; p=[insert]). CSF IL‑1β increased after TBI and was reduced by NOB 25 and 50 mg/kg ([insert values], p=[insert]); IL‑10 decreased after TBI and was increased by NOB 25 and 50 mg/kg ([insert], p=[insert]). The 100 mg/kg dose showed limited or no benefit across endpoints. Histology revealed attenuated neuronal edema/pyknosis and vascular congestion with NOB 25–50 mg/kg; [if scored] injury scores were reduced vs TBI/Vehicle (p=[insert]).
Conclusion: A single post‑injury dose of nobiletin at 25–50 mg/kg improved neurological outcomes and mitigated edema, BBB disruption, histopathology, and cytokine imbalance within 72 h after severe diffuse TBI, with 50 mg/kg showing the most consistent efficacy. The 100 mg/kg dose was not beneficial. Findings support anti‑inflammatory and vasculoprotective actions of nobiletin in acute TBI.
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2025/07/27 | Accepted: 2026/05/25
Received: 2025/07/27 | Accepted: 2026/05/25
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