Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation
Background: Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, and psychological impairments, triggering oxidative stress, neuroinflammation, and neurodegeneration. This study examined the neuroprotective effects of azithromycin...
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2025-01-01
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| author | Mohannad A. Almikhlafi Nehad A. Abdallah Aakash Kumar Tarun Sharma Zuber Khan Haifa A. Fadil Sultan Althagfan Ahmed K. B. Aljohani Sara A. Almadani Samar F. Miski Tahani Saeedi Rayan S. Alharbi Abdulrahman M. Al-Harthe Mohammed H. Alsubhi Hanaa Wanas Ahmed Aldhafiri Sidharth Mehan Hossein M. Elbadawy |
| author_facet | Mohannad A. Almikhlafi Nehad A. Abdallah Aakash Kumar Tarun Sharma Zuber Khan Haifa A. Fadil Sultan Althagfan Ahmed K. B. Aljohani Sara A. Almadani Samar F. Miski Tahani Saeedi Rayan S. Alharbi Abdulrahman M. Al-Harthe Mohammed H. Alsubhi Hanaa Wanas Ahmed Aldhafiri Sidharth Mehan Hossein M. Elbadawy |
| author_sort | Mohannad A. Almikhlafi |
| collection | DOAJ |
| description | Background: Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, and psychological impairments, triggering oxidative stress, neuroinflammation, and neurodegeneration. This study examined the neuroprotective effects of azithromycin (AZI) in TBI. Methods: TBI was induced in rats using the weight-drop method. Subsequently, rats received a daily intraperitoneal (I.P.) dose of AZI (150 mg/kg) for 28 days. Behavioral tests (Morris water maze, rotarod, and open field tests) were performed to assess cognitive and motor functions. Neurochemical analyses included oxidative stress markers (GSH, SOD, MDA, catalase), inflammatory cytokines (TNF-α, IL-1β), apoptotic markers (caspase-3, Bax, Bcl-2), mitochondrial complexes (complex I, II, III, IV, and V), and the transforming growth factor- beta (TGF-β) as a neurofilament marker. Histological evaluations focused on neuronal integrity in the cortex, hippocampus, and striatum. Results: Treatment with AZI significantly facilitated motor and cognitive function recovery in TBI-affected rats. At the molecular level, AZI effectively reduced oxidative stress markers, ameliorated neuroinflammation by decreasing TNF-α, IL-1β, and neuronal apoptosis, and differentially modulated mitochondrial complexes. Histological assessments revealed enhanced neuronal integrity and fewer pathological changes in AZI-treated rats compared to untreated TBI controls. Conclusions: AZI was shown to interfere with several pathways involved in TBI’s pathophysiology. While preclinical results are promising, further studies are necessary to establish the long-term safety and efficacy of AZI in a clinical setting. This research supports the potential re-purposing of AZI as a novel treatment strategy for TBI and related neurodegenerative disorders. |
| format | Article |
| id | doaj-art-8a11734dc8e840309bd0fd3aac08a67c |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-8a11734dc8e840309bd0fd3aac08a67c2025-01-24T13:45:27ZengMDPI AGPharmaceuticals1424-82472025-01-0118111510.3390/ph18010115Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory ModulationMohannad A. Almikhlafi0Nehad A. Abdallah1Aakash Kumar2Tarun Sharma3Zuber Khan4Haifa A. Fadil5Sultan Althagfan6Ahmed K. B. Aljohani7Sara A. Almadani8Samar F. Miski9Tahani Saeedi10Rayan S. Alharbi11Abdulrahman M. Al-Harthe12Mohammed H. Alsubhi13Hanaa Wanas14Ahmed Aldhafiri15Sidharth Mehan16Hossein M. Elbadawy17Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, Punjab, IndiaDepartment of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, Punjab, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 41477, Saudi ArabiaBackground: Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, and psychological impairments, triggering oxidative stress, neuroinflammation, and neurodegeneration. This study examined the neuroprotective effects of azithromycin (AZI) in TBI. Methods: TBI was induced in rats using the weight-drop method. Subsequently, rats received a daily intraperitoneal (I.P.) dose of AZI (150 mg/kg) for 28 days. Behavioral tests (Morris water maze, rotarod, and open field tests) were performed to assess cognitive and motor functions. Neurochemical analyses included oxidative stress markers (GSH, SOD, MDA, catalase), inflammatory cytokines (TNF-α, IL-1β), apoptotic markers (caspase-3, Bax, Bcl-2), mitochondrial complexes (complex I, II, III, IV, and V), and the transforming growth factor- beta (TGF-β) as a neurofilament marker. Histological evaluations focused on neuronal integrity in the cortex, hippocampus, and striatum. Results: Treatment with AZI significantly facilitated motor and cognitive function recovery in TBI-affected rats. At the molecular level, AZI effectively reduced oxidative stress markers, ameliorated neuroinflammation by decreasing TNF-α, IL-1β, and neuronal apoptosis, and differentially modulated mitochondrial complexes. Histological assessments revealed enhanced neuronal integrity and fewer pathological changes in AZI-treated rats compared to untreated TBI controls. Conclusions: AZI was shown to interfere with several pathways involved in TBI’s pathophysiology. While preclinical results are promising, further studies are necessary to establish the long-term safety and efficacy of AZI in a clinical setting. This research supports the potential re-purposing of AZI as a novel treatment strategy for TBI and related neurodegenerative disorders.https://www.mdpi.com/1424-8247/18/1/115azithromycintraumatic brain injuryneuroprotection |
| spellingShingle | Mohannad A. Almikhlafi Nehad A. Abdallah Aakash Kumar Tarun Sharma Zuber Khan Haifa A. Fadil Sultan Althagfan Ahmed K. B. Aljohani Sara A. Almadani Samar F. Miski Tahani Saeedi Rayan S. Alharbi Abdulrahman M. Al-Harthe Mohammed H. Alsubhi Hanaa Wanas Ahmed Aldhafiri Sidharth Mehan Hossein M. Elbadawy Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation Pharmaceuticals azithromycin traumatic brain injury neuroprotection |
| title | Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation |
| title_full | Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation |
| title_fullStr | Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation |
| title_full_unstemmed | Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation |
| title_short | Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation |
| title_sort | exploring azithromycin s neuroprotective role in traumatic brain injury insights into cognitive and motor recovery and neuroinflammatory modulation |
| topic | azithromycin traumatic brain injury neuroprotection |
| url | https://www.mdpi.com/1424-8247/18/1/115 |
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