Journal of Nutrition,Fasting and Health

Journal of Nutrition,Fasting and Health

The Effect of Aerobic Exercise on Some Angiogenic Markers in Brain Tissue in an Experimental Autoimmune Encephalomyelitis Model

Document Type : Research Paper

Authors
Mehran Abasnejad
Zaher Etemad
Kamal Azizbeigi
Khalid Mohammadzadeh Salamat
Department of Physical Education and Sport Sciences, Sa.C., Islamic Azad University, Sanandaj, Iran.
10.22038/jnfh.2026.93305.1614
Abstract
Introduction: Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, involves neuroinflammation and cerebrovascular dysfunction. However, the impact of exercise on cerebral angiogenic and vasoactive mediators remains unclear. Therefore, the present study aimed to investigate the effects of a five-week endurance training (ET) protocol on the gene expression levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in brain tissue in an experimental model of EAE. Methods: In this experimental study, fourteen female Sprague–Dawley rats with EAE (induced using complete Freund’s adjuvant) were randomly assigned to either the EAE (n=7) or EAE+ET (n=7) groups. To assess baseline differences, seven healthy rats were included as a healthy control group (HC). Endurance training started ten days after EAE induction. Rats underwent one week of treadmill familiarization (6 m/min,11% incline,5–25min/day), followed by five weeks of moderate-intensity running (11 m/min, 30 min/day, 5 sessions/week). Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test (P≤ 0.05). Results: The gene expression levels of VEGF and ET-1 were significantly higher in the EAE group compared to the HC group (P = 0.001). However, both VEGF and ET-1 expression were markedly reduced in the EAE+ET group relative to the EAE group (P ≤ 0.05). Conclusion: The findings suggest that endurance exercise may exert beneficial effects by attenuating inflammatory responses and angiogenic activity in brain tissue following EAE induction. Nonetheless, given the limited evidence on how exercise modulates VEGF and ET-1 expression in the brain under autoimmune conditions, further research is warranted.
Keywords
Exercise
VEGF
ET-1
Nervous System Autoimmune Disease
Experimental
Subjects
  1. Moghtaderi A, Shahidi-Pourakbari M, Izadi S, Khosravi A, Hashemzehi Z. Ongoing increase in incidence and prevalence of multiple sclerosis in south-eastern Iran: A three decade study. Mult Scler Relat Disord. 2023;71:104557.
  2. Calvillo-Robledo A, Ramírez-Farías C, Valdez-Urias F, Huerta-Carreón EP, Quintanar-Stephano A. Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment. Front Neurosci. 2023;17:1138627.
  3. J Karlik S, A Roscoe W, Patinote C, Contino-Pepin C. Targeting vascular changes in lesions in multiple sclerosis and experimental autoimmune encephalomyelitis. Cent Nerv Syst Agents Med Chem (Formerly Curr Med Chem Nerv Syst Agents). 2012;12(1):7–14.
  4. Girolamo F, Coppola C, Ribatti D, Trojano M. Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol Commun. 2014;2(1):84.
  5. Jin Y-H, Kang B, Kang HS, Koh C-S, Kim BS. Endothelin-1 contributes to the development of virus-induced demyelinating disease. J Neuroinflammation. 2020;17(1):307.
  6. Ghanbari P, Khajehzadeh S, Sayyed A, Raeisi D, Salehi O. The effect of high intensity interval training with beetroot (Beta vulgaris) juice supplementation on serotonin and dopamine receptors expression, anxiety and depression in middle-aged diabetic rats. Avicenna J Phytomedicine. 2022;12(6).
  7. Salehi O, Sheikholeslami-Vatani D, Hosseini SA. Positive effects of HIIT and vitamin E on cognitive function, angiogenesis and NRF2 antioxidant pathway in male rats with Alzheimer’s disease. Biogerontology. 2025;26(4):129.
  8. Einstein O, Katz A, Ben-Hur T. Physical exercise therapy for autoimmune neuroinflammation: Application of knowledge from animal models to patient care. Autoimmun Rev. 2022;21(4):103033.
  9. Sohrabi P, Parnow A, Jalili C. Treadmill aerobic training improve beam-walking test, up-regulate expression of main proteins of myelin and myelination in the hippocampus of cuprizone-fed mice. Neurosci Lett. 2023;792:136936.
  10. Goldberg Y, Segal S, Hamdi L, Nabat H, Fainstein N, Mediouni E, et al. High-intensity interval training attenuates development of autoimmune encephalomyelitis solely by systemic immunomodulation. Sci Rep. 2023;13(1):16513.
  11. Hamdi L, Nabat H, Goldberg Y, Fainstein N, Segal S, Mediouni E, et al. Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis. Ann Clin Transl Neurol. 2022;9(11):1792–806.
  12. Rezaee S, Kahrizi S, Nabavi SM, Hedayati M. VEGF and TNF-α Responses to Acute and Chronic Aerobic Exercise in the Patients with Multiple Sclerosis. Asian J Sports Med. 2020;11(3).
  13. Yaghoubi M, Kordi M, Gaeini A. The Effect of Forced and Voluntary Exercise before Induction of Experimental Autoimmune Encephalomyelitis on the Integrity of the Blood-Brain Barrier and Gene Expression of Some of Tight Junction Proteins. J Appl Exerc Physiol. 2020;16(32):87–101.
  14. Tajiri N, Yasuhara T, Shingo T, Kondo A, Yuan W, Kadota T, et al. Exercise exerts neuroprotective effects on Parkinson’s disease model of rats. Brain Res. 2010;1310:200–7.
  15. Bernardes D, Oliveira ALR de. Regular exercise modifies histopathological outcomes of pharmacological treatment in experimental autoimmune encephalomyelitis. Front Neurol. 2018;9:950.
  16. D’Orléans-Juste P, Ndunge OBA, Desbiens L, Tanowitz HB, Desruisseaux MS. Endothelins in inflammatory neurological diseases. Pharmacol Ther. 2019;194:145–60.
  17. Yin X-X, Zheng X-R, Peng W, Wu M-L, Mao X-Y. Vascular endothelial growth factor (VEGF) as a vital target for brain inflammation during the COVID-19 outbreak. ACS Chem Neurosci. 2020;11(12):1704–5.
  18. Włodarczyk L, Cichoń N, Karbownik MS, Saso L, Saluk J, Miller E. Circulating serum VEGF, IGF-1 and MMP-9 and expression of their genes as potential prognostic markers of recovery in post-stroke rehabilitation—a prospective observational study. Brain Sci. 2023;13(6):846.
  19. Ali M, Falkenhain K, Njiru BN, Murtaza-Ali M, Ruiz-Uribe NE, Haft-Javaherian M, et al. VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer’s mice. Brain. 2022;145(4):1449–63.
  20. Yu Q, Xia Z, Liong EC, Tipoe GL. Chronic aerobic exercise improves insulin sensitivity and modulates Nrf2 and NF‑κB/IκBα pathways in the skeletal muscle of rats fed with a high fat diet. Mol Med Rep. 2019;20(6):4963–72.
  21. Wenner MM, Welti LM, Dow CA, Greiner JJ, Stauffer BL, DeSouza CA. Aerobic exercise training reduces ET-1-mediated vasoconstriction and improves endothelium-dependent vasodilation in postmenopausal women. Am J Physiol Circ Physiol. 2023;324(6):H732–8.
Journal of Nutrition,Fasting and Health
Volume 14, Issue 3
Summer 2026
Pages 210-217

  • Receive Date 04 December 2025
  • Revise Date 28 February 2026
  • Accept Date 10 June 2026