Original Articles
Vol. 5 No. 2 (2026)
Neurovascular protective effects of nutritional interventions in ischemic brain injury
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 10 April 2026
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Background: Cerebral ischemia/reperfusion (I/R) injury is marked by oxidative stress, inflammation, and neuronal loss. Natural antioxidants such as fish oil and Nigella sativa oil have shown potential neuroprotective properties. This study evaluated the individual and combined effects of these oils in a mouse model of cerebral ischemia.
Methods: Forty mice were randomly assigned to five groups: sham, I/R, Nigella sativa oil, fish oil, and combined treatment. Cerebral ischemia was induced by 17 min bilateral common carotid artery occlusion followed by reperfusion. Treatments were administered orally. Motor coordination and cognitive function were assessed using behavioral tests, while neuronal damage was evaluated histologically. Oxidative stress markers (MDA, GSH, SOD) and the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) were measured in brain tissue.
Results: All treated groups showed significant improvements in motor and cognitive performance compared with the I/R group. Treatments reduced MDA and TNF-α levels and increased GSH and SOD activity. Histopathological analysis revealed attenuated hippocampal neuronal damage, with the combination therapy showing the greatest protection.
Conclusions: Combined fish oil and Nigella sativa oil therapy provides enhanced neuroprotection against cerebral I/R injury and may represent a supportive strategy for reducing ischemic brain damage.
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Citations
1. Zainuddin AA, Kadir RR, Kuswanto H, et al. The major risk factor of stroke across Indonesia: a nationwide geospatial analysis of universal health coverage program. Arch Public Health 2025;83:169. DOI: https://doi.org/10.1186/s13690-025-01613-4
2. Diji PK, Zhicheng Y. The management of stroke and associated factors. J Acute Dis 2020;9:106-14.
3. Kuriakose D, Xiao Z. Pathophysiology and treatment of stroke: present status and future perspectives. Int J Mol Sci 2020;21:7609. DOI: https://doi.org/10.3390/ijms21207609
4. Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization global stroke fact sheet 2022. Int J Stroke 2022;17:18-29. DOI: https://doi.org/10.1177/17474930211065917
5. Lisha J, Saravanana J, Santilna KS, et al. Neuroprotective activity of farnesol against bilateral common carotid artery occlusion induced cerebral ischemia/reperfusion injury in mice. Lat Am J Pharm 2019;38:572-8.
6. Bersano A, Gatti L. Pathophysiology and treatment of stroke: present status and future perspectives. Int J Mol Sci 2023;24:14848. DOI: https://doi.org/10.3390/ijms241914848
7. Patel D, Wairkar S. Biotechnology-based therapeutics for management of cerebral stroke. Eur J Pharmacol 2021;913:174638. DOI: https://doi.org/10.1016/j.ejphar.2021.174638
8. Liguz-Lecznar M, Kossut M. Influence of inflammation on stroke pathogenesis and its implications for therapy. J Neuroinflammation 2013;10:1-3. DOI: https://doi.org/10.1155/2013/258582
9. Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol 2017;133:245-61. DOI: https://doi.org/10.1007/s00401-017-1667-0
10. Wang L, Zhang T, Li W, et al. The model of bilateral common carotid artery occlusion induced cerebral ischemia. J Vis Exp 2021;168:e62368.
11. Khaliq A, Hafeez-ur-Rehman M, Abbas F, et al. Omega-3 fatty acids, lecithin, sterols, vitamins and lipid oxidation of olein and super olein fractions of fish oil produced by winterization. Food Sci Nutr 2025;13:e4754. DOI: https://doi.org/10.1002/fsn3.4754
12. Oppedisano F, Macrì R, Gliozzi M, et al. The anti-inflammatory and antioxidant properties of n-3 PUFAs: their role in cardiovascular protection. Biomedicines 2020;8:306. DOI: https://doi.org/10.3390/biomedicines8090306
13. Zirpoli H, Bernis ME, Sabir H, et al. Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury. Biomed Pharmacother 2024;175:116749. DOI: https://doi.org/10.1016/j.biopha.2024.116749
14. Soleimannejad K, Rahmani A, Hatefi M, et al. Effects of Nigella sativa extract on markers of cerebral angiogenesis after global ischemia of brain in rats. J Stroke Cerebrovasc Dis 2017;26:1514-20. DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.02.040
15. Mihaylova A, Doncheva N, Vlasheva M, et al. Investigation of the immunomodulatory and neuroprotective properties of Nigella sativa oil in experimental systemic and neuroinflammation. Int J Mol Sci 2025;26:2235. DOI: https://doi.org/10.3390/ijms26052235
16. Al-Okbi SY, Mohamed DA, Hamed TE, et al. Hepatic regeneration and reno-protection by fish oil, Nigella sativa oil and combined fish oil/Nigella sativa volatiles in CCL4 treated rats. J Oleo Sci 2018;67:345-53. DOI: https://doi.org/10.5650/jos.ess17204
17. Kakae M, Kawashita A, Onogi H, et al. Bilateral common carotid artery stenosis in mice: a model of chronic cerebral hypoperfusion-induced vascular cognitive impairment. Bio Protoc 2024;14:e5022. DOI: https://doi.org/10.21769/BioProtoc.5022
18. Washida K, Ihara M, Nishio K, et al. Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor gamma activation in mice with chronic cerebral hypoperfusion. Stroke 2010;41:1798-806. DOI: https://doi.org/10.1161/STROKEAHA.110.583948
19. Sawers A, Hafner B. Validation of the narrowing beam walking test in lower limb prosthesis users. Arch Phys Med Rehabil 2018;99:1491-8. DOI: https://doi.org/10.1016/j.apmr.2018.03.012
20. Moghaddam AH, Pour YS, Sangdehi SR, et al. Evaluation of hesperetin-loaded on multiple wall carbon nanotubes on cerebral ischemia/reperfusion injury in rats. Biomed Pharmacother 2021;138:111467. DOI: https://doi.org/10.1016/j.biopha.2021.111467
21. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8. DOI: https://doi.org/10.1016/0003-2697(79)90738-3
22. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979;582:67-78. DOI: https://doi.org/10.1016/0304-4165(79)90289-7
23. Marklund SL. Extracellular superoxide dismutase and other superoxide dismutase isoenzymes in tissues from nine mammalian species. Biochem J 1984;222:649-55. DOI: https://doi.org/10.1042/bj2220649
24. Sharma D, Verma S, Vaidya S, et al. Recent updates on GLP-1 agonists: current advancements and challenges. Biomed Pharmacother 2018;108:952-62. DOI: https://doi.org/10.1016/j.biopha.2018.08.088
25. Sharma N, Nehru B. Characterization of the lipopolysaccharide-induced model of Parkinson’s disease: role of oxidative stress and neuroinflammation. Neurochem Int 2015;87:92-105. DOI: https://doi.org/10.1016/j.neuint.2015.06.004
26. Shi X, Bai H, Wang J, et al. Behavioral assessment of sensory, motor, emotion, and cognition in rodent models of intracerebral hemorrhage. Front Neurol 2021;12:667511. DOI: https://doi.org/10.3389/fneur.2021.667511
27. Gureev AP, Sadovnikova IS, Chernyshova EV, et al. Beta-hydroxybutyrate mitigates sensorimotor and cognitive impairments in a photothrombosis-induced ischemic stroke in mice. Int J Mol Sci 2024;25:5710. DOI: https://doi.org/10.3390/ijms25115710
28. Govori V, Budinčević H, Morović S, et al. Updated perspectives on lifestyle interventions as secondary stroke prevention measures: a narrative review. Medicina 2024;60:504. DOI: https://doi.org/10.3390/medicina60030504
29. Mahboub HH, Elsheshtawy HM, Sheraiba NI, et al. Dietary black cumin improved hemato-biochemical, oxidative stress, gene expression, and immunological response of Nile tilapia infected by Burkholderia cepacia. Aquac Rep 2022;22:100943. DOI: https://doi.org/10.1016/j.aqrep.2021.100943
30. Yousefi M, Adineh H, Reverter M, et al. Protective effects of black seed diet supplementation in common carp against immune depression, oxidative stress and metabolism dysfunction induced by glyphosate. Fish Shellfish Immunol 2021;109:12-9. DOI: https://doi.org/10.1016/j.fsi.2020.11.032
31. Galeone A, Grano M, Brunetti G. Tumor necrosis factor family members and myocardial ischemia-reperfusion injury: state of the art and therapeutic implications. Int J Mol Sci 2023;24:4606. DOI: https://doi.org/10.3390/ijms24054606
32. Mi R, Cheng H, Chen R, et al. Effects and mechanisms of long-acting GLP-1 receptor agonist semaglutide on microglia phenotypic transformation and neuroinflammation after cerebral ischemia/reperfusion in rats. Brain Circ 2024;10:354-65. DOI: https://doi.org/10.4103/bc.bc_38_24
33. Einenkel AM, Salameh A. Selective vulnerability of hippocampal CA1 and CA3 pyramidal cells: pathomechanisms and implications. J Neurosci Res 2024;102:e25276. DOI: https://doi.org/10.1002/jnr.25276
34. Sadeghi E, Imenshahidi M, Hosseinzadeh H. Molecular mechanisms and signaling pathways of black cumin and thymoquinone: a review. Mol Biol Rep 2023;50:5439-54. DOI: https://doi.org/10.1007/s11033-023-08363-y
35. Fernandes LC, Costa IM, Freire MA, et al. Essential oils in experimental models of neuropsychiatric disorders: a systematic review. Curr Neuropharmacol 2021;19:1738-59. DOI: https://doi.org/10.2174/1570159X19666210421091734
Ethics Approval
The study protocol was approved by the Institutional Animal Ethics Committee of Raj Kumar Goel Institute of Technology (Pharmacy) with approval no. RKGIT/IAEC/2024/08.CRediT authorship contribution
GM conceptualized the study, supervised the investigation, reviewed, and edited the manuscript. PM conducted the experimental work, data analysis, and drafted the manuscript. SS performed statistical analyses, histological examination, and contributed to the manuscript writing. RT critically reviewed and edited the manuscript. MS arranged all the necessary resources, supervised the investigation, and reviewed the manuscript. All the authors reviewed and approved the final version of the manuscript.
Data Availability Statement
All data generated or analyzed during this study are included in this published article.
How to Cite
1.
Mehta G, Mishra P, Sharma S, Tripathi R, Sachdeva M. Neurovascular protective effects of nutritional interventions in ischemic brain injury. Bleeding Thromb Vasc Biol [Internet]. 2026 Apr. 10 [cited 2026 May 6];5(2). Available from: https://www.btvb.org/btvb/article/view/436
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