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Original Article
Online Published: 10 Sep 2026
 


Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats

Shatha S. Shaker, Shahad N. Khabbaz, Al-yakthan A. Salih, Anas Y. Al-hayawi, Reham Alwash, Rasha I. Almoussawi.


Abstract
Despite proven influence of inflammatory bowel disease (IBD) on the gut-brain axis leading to sickness behaviours such as anorexia, fatigue, the change in the neurometabolic system in the hypothalamus has not been studied closely. The aim of this study is to observe the changes in the hypothalamus. Materials and Methods: Forty-eight male Sprague-Dawley rats were randomly allocated to two groups (n = 8 per group per time point): vehicle control and TNBS-induced colitis, and assessed at Day 3 (acute), Day 7 (peak), and Day 14 (resolution). Hypothalamic tissue was analysed by Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy, RNA sequencing, and Iba-1/c-Fos immunofluorescence; Disease Activity Index, histopathology, and ELISA for TNF-α, IL-1β, and IL-6 quantified colonic inflammation. Data were analysed by two-way ANOVA with Tukey post hoc test and Spearman rank correlation, with significance set at P < 0.05. Results: TNBS-treated rats exhibited peak weight loss (-12.8%) and colon shortening (9.5 ± 0.7 cm vs 16.4 ± 0.5 cm in controls) at Day 7. Hypothalamic glutamate and GABA were significantly reduced at peak inflammation (both P < 0.001), while the kynurenine/tryptophan ratio tripled and correlated closely with colonic TNF-α/IL-1β levels (r(16) = 0.88, P < 0.001). Microglia adopted an activated morphology in the arcuate and paraventricular nuclei at peak disease, and locomotor suppression persisted to Day 14 despite partial intestinal recovery. Conclusion: There is a temporal connection between peripheral intestinal inflammation and neurological-neuroimmunological alterations in the hypothalamus in TNBS-induced colitis. The presented pathways representation for further investigation for possible mechanism rather than established cause of the phenomenon.

Key words: Brain-Gut Axis; GABA; Hypothalamus; Metabolomics; Microglia; TNBS Colitis


 
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How to Cite this Article
Pubmed Style

Shaker SS, Khabbaz SN, Salih AA, Al-hayawi AY, Alwash R, Almoussawi RI. Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. AJVS. Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684

Web Style

Shaker SS, Khabbaz SN, Salih AA, Al-hayawi AY, Alwash R, Almoussawi RI. Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. https://www.alexjvs.com/?mno=325684 [Access: September 10, 2026]. doi:10.5455/ajvs.325684

AMA (American Medical Association) Style

Shaker SS, Khabbaz SN, Salih AA, Al-hayawi AY, Alwash R, Almoussawi RI. Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. AJVS. Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684


Vancouver/ICMJE Style

Shaker SS, Khabbaz SN, Salih AA, Al-hayawi AY, Alwash R, Almoussawi RI. Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. AJVS, [cited September 10, 2026]; Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684


Harvard Style

Shaker, S. S., Khabbaz, . S. N., Salih, . A. A., Al-hayawi, . A. Y., Alwash, . R. & Almoussawi, . R. I. (0) Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. AJVS, Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684


Turabian Style

Shaker, Shatha S., Shahad N. Khabbaz, Al-yakthan A. Salih, Anas Y. Al-hayawi, Reham Alwash, and Rasha I. Almoussawi. 0. Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. Alexandria Journal of Veterinary Sciences, Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684


Chicago Style

Shaker, Shatha S., Shahad N. Khabbaz, Al-yakthan A. Salih, Anas Y. Al-hayawi, Reham Alwash, and Rasha I. Almoussawi. "Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats." Alexandria Journal of Veterinary Sciences Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684


MLA (The Modern Language Association) Style

Shaker, Shatha S., Shahad N. Khabbaz, Al-yakthan A. Salih, Anas Y. Al-hayawi, Reham Alwash, and Rasha I. Almoussawi. "Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats." Alexandria Journal of Veterinary Sciences Online First: 10 Sep, 2026. Web. 10 Sep 2026 doi:10.5455/ajvs.325684


APA (American Psychological Association) Style

Shaker, S. S., Khabbaz, . S. N., Salih, . A. A., Al-hayawi, . A. Y., Alwash, . R. & Almoussawi, . R. I. (0) Longitudinal Characterization of Hypothalamic Neurometabolic and Neuroinflammatory Responses to TNBS-Induced Colitis in Sprague-Dawley Rats. Alexandria Journal of Veterinary Sciences, Online First: 10 Sep, 2026. doi:10.5455/ajvs.325684




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    The Alexandria Journal of Veterinary Sciences (AJVS) Official Journal of Faculty of Veterinary Medicine, Alexandria University   ISSN: 1110-204 ... Read more.



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    Egypt.

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