The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB
Khodir, S., El-Haroun, H., Shukry, A., H. Abd-Elhamid, T., Seddek, A., Samy, E., R. Mahmoud, A., Nabil, A., Ahmed, K. (2025). The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB. EKB Journal Management System, 45(1), 18-31. doi: 10.21608/besps.2024.324333.1179
Suzan A Khodir; Hala El-Haroun; Asmaa Mahmoud Shukry; Tarek H. Abd-Elhamid; Asmaa Abdellatef Seddek; Eman Samy; Amany R. Mahmoud; Amaal Nabil; Karima El-Sayed Ahmed. "The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB". EKB Journal Management System, 45, 1, 2025, 18-31. doi: 10.21608/besps.2024.324333.1179
Khodir, S., El-Haroun, H., Shukry, A., H. Abd-Elhamid, T., Seddek, A., Samy, E., R. Mahmoud, A., Nabil, A., Ahmed, K. (2025). 'The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB', EKB Journal Management System, 45(1), pp. 18-31. doi: 10.21608/besps.2024.324333.1179
Khodir, S., El-Haroun, H., Shukry, A., H. Abd-Elhamid, T., Seddek, A., Samy, E., R. Mahmoud, A., Nabil, A., Ahmed, K. The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB. EKB Journal Management System, 2025; 45(1): 18-31. doi: 10.21608/besps.2024.324333.1179

The Rho Kinase Inhibitor Fasudil Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging in Rats: Involvement of SIRT1, BDNF and NF-κB

Bulletin of Egyptian Society for Physiological Sciences
Volume 45, Issue 1, January 2025, Pages 18-31    PDF (1.01 M)
Document Type: Review Article
DOI: 10.21608/besps.2024.324333.1179
Authors
Suzan A Khodir1; Hala El-Haroun2; Asmaa Mahmoud Shukry3; Tarek H. Abd-Elhamid4; Asmaa Abdellatef Seddek5; Eman Samy6; Amany R. Mahmoud7; Amaal Nabil8; Karima El-Sayed Ahmed* 5
1Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
2Histology and Cell Biology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia
3Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Menoufia University
4Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
5Medical Physiology Department, Faculty of Medicine, Suez Canal University
6Neuropsychiatry Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia
7Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
8Medical Pharmacology Department, Faculty of medicine, Suez Canal University Ismailia, Egypt
Abstract
Abstract
Introduction: Cognitive deficits and aging were evoked by D-galactose (D-gal). Fasudil (Fsd) slows the start and progress of neurodegenerative illnesses.
Objective: to illustrate the neuroprotective effect of Fsd in D-gal induced cognitive deficits and the underling mechanisms involved
Material & methods: Thirty Wister albino male rats divided into control, D-gal, D-gal+Fsd groups. Rats were subjected to MWM, NOR and EPM tests then rats were sacrificed and MDA, catalase, TNF-α, IL-6 hippocampal gene expression of BDNF, SIRT1 and NF-kB were assessed. Histopathological and immunoreaction for caspase-3 and GFAP were done.
Results: D-gal revealed cognitive impairment, with substantial elevation of MDA, TNF-α, IL-6 and NF-kB gene expression and significant reduction of catalase, SIRT1 and BDNF gene expression of D-gal with upregulation of caspase-3 and GFAP immunoreaction in hippocampus. Fsd dramatically improved D-gal induced changes.
Conclusion: Fsd alleviated D-gal induced cognitive deficits by anti-oxidant, anti-inflammatory, anti-apoptotic mechanisms in addition to up-regulation of Sirt1 and BDNF gene expression and improving gliosis.
Keywords
SIRT1; BDNF; GFAP; D-galactose; Fasudil and NF-κB
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