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Peer-reviewedCC BY-NC 4.0Animal Models and Experimental Medicine

Neuroprotection after transient middle cerebral artery occlusion in male rats using kojic acid nanostructured lipid carriers: A behavioral, biochemical, and histological study on hippocampal CA1 region

12 affiliations
  1. 1Student Research Committee, School of Allied Medical Sciences Mazandaran University of Medical Sciences Sari Iran
  2. 2Non‐Communicable Diseases Institute, Mazandaran University of Medical Sciences Sari Iran
  3. 3Student Research Committee, School of Medicine Mazandaran University of Medical Sciences Sari Iran
  4. 4Department of Clinical Sciences, School of Veterinary Medicine Shiraz University Shiraz Iran
  5. 5Department of Basic Medical Sciences Khoy University of Medical Sciences Khoy Iran
  6. 6Student Research Committee Khoy University of Medical Sciences Khoy Iran
  7. 7Department of Pharmaceutics, School of Pharmacy Mazandaran University of Medical Sciences Sari Iran
  8. 8Immunogenetics Research Center Mazandaran University of Medical Sciences Sari Iran
  9. 9Psychiatry and Behavioral Sciences Research Center Addiction Institute, Mazandaran University of Medical Sciences Sari Iran
  10. 10Department of Neurology Mazandaran University of Medical Sciences Sari Iran
  11. 11Student Research Committee, School of Pharmacy Mazandaran University of Medical Sciences Sari Iran
  12. 12Department of Cardiology Shiraz University of Medical Sciences Shiraz Iran

Abstract

Background: Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA‐NLC) exerts protective effects against cerebral ischemia.

Methods: Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (n = 8 per group): intact, sham, MCAO, vehicle, three free‐KA solution groups (10, 20, and 40 mg/kg), and three KA‐NLC groups (1, 2, and 4 mg/kg). Functional outcomes were assessed using neurological scoring and Rota‐Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin‐10 [IL‐10], tumor necrosis factor‐α [TNF‐α]) were also evaluated.

Results: Treatment with low and medium doses of KA‐NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti‐inflammatory IL‐10 and a modulation of TNF‐α. Histological examination confirmed neuroprotection, with KA‐NLC preserving hippocampal CA1 neural integrity. The high dose of KA‐NLC and the low dose of free KA however were ineffective.

Conclusions: Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.

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BibTeX
@article{gheibi2026neuroprotection,
  title = {{Neuroprotection after transient middle cerebral artery occlusion in male rats using kojic acid nanostructured lipid carriers: A behavioral, biochemical, and histological study on hippocampal CA1 region}},
  author = {Mobina Gheibi and Erfan Ghadirzadeh and Javid Tebyani and Seyedeh Mohadeseh Moyaedi and Khadijeh Khezri and Majid Saeedi and Ali Siahposht‐Khachaki and Narges Karimi and Melika Pourhossein and Shiva Shadi and Sasan Shafiei and Atena Sharifi‐Razavi},
  journal = {Animal Models and Experimental Medicine},
  year = {2026},
  month = sep,
  doi = {10.1002/ame2.70285},
  url = {https://doi.org/10.1002/ame2.70285},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Neuroprotection after transient middle cerebral artery occlusion in male rats using kojic acid nanostructured lipid carriers: A behavioral, biochemical, and histological study on hippocampal CA1 region
AU  - Mobina Gheibi
AU  - Erfan Ghadirzadeh
AU  - Javid Tebyani
AU  - Seyedeh Mohadeseh Moyaedi
AU  - Khadijeh Khezri
AU  - Majid Saeedi
AU  - Ali Siahposht‐Khachaki
AU  - Narges Karimi
AU  - Melika Pourhossein
AU  - Shiva Shadi
AU  - Sasan Shafiei
AU  - Atena Sharifi‐Razavi
PY  - 2026
DA  - 2026/09/01
JO  - Animal Models and Experimental Medicine
DO  - 10.1002/ame2.70285
UR  - https://doi.org/10.1002/ame2.70285
AB  - Background: Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA‐NLC) exerts protective effects against cerebral ischemia.  Methods: Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (n = 8 per group): intact, sham, MCAO, vehicle, three free‐KA solution groups (10, 20, and 40 mg/kg), and three KA‐NLC groups (1, 2, and 4 mg/kg). Functional outcomes were assessed using neurological scoring and Rota‐Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin‐10 [IL‐10], tumor necrosis factor‐α [TNF‐α]) were also evaluated.  Results: Treatment with low and medium doses of KA‐NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti‐inflammatory IL‐10 and a modulation of TNF‐α. Histological examination confirmed neuroprotection, with KA‐NLC preserving hippocampal CA1 neural integrity. The high dose of KA‐NLC and the low dose of free KA however were ineffective.  Conclusions: Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.
SN  - 2096-5451
SN  - 2576-2095
ER  -