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Compromised blood-brain barrier in traumatic brain injury model of Danio rerio: A unique window to demonstrate restoration of behavioral, cellular, and neurochemical deficits by limonin
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DOI：10.22038/ijbms.2026.90876.19603.png)
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Abstract
En 中文
Objective(s): Traumatic Brain Injury (TBI) poses a significant risk factor for various neurological complications, ranging from acute manifestations in severe cases to insidious onset in mild instances, often leading to fatal outcomes with elusive aetiologies until post-mortem examination. Limonin, a secondary metabolite renowned for mitigating metabolic syndrome risk factors, notably cardiovascular complications and fatty liver disease, demonstrates promising neuroprotective properties in vitro. This study aimed to elucidate the in vivo neuromodulatory effects of limonin using an adult zebrafish model. Materials and Methods: The compound was evaluated for toxicity to zebrafish using the comet assay and phenotypic assessment. Through a series of assays encompassing behavioral, histological, and biochemical analyses, rescue from cell death was observed in adjacent regions despite the native regenerative background of a wild-type zebrafish. A novel brain cell suspension from adult zebrafish was also employed to discover rescue against necrotic cell death cues. Results: Lipid peroxidation-induced neuroinflammation and 2-fold reduction of free radicals, compared with TBI controls, were observed with 300 & micro;M Limonin treatment. The cell viability assay performed, indicated at least 5-fold reduction in the cell damage due to brain injury. Histopathological sectioning and staining showed reduction in inflammatory cell infiltration and demyelination demonstrating the anti-inflammatory and neuroprotective properties of limonin. We also demonstrated behavioral changes associated with TBI that can be alleviated by limonin treatment. Conclusion: These findings underscore the potential of limonin as a potent neuromodulator and warrant further preclinical investigations to mitigate TBI-associated neurological deficits.
Keywords:
Limonin
Microglial cell
Phytochemicals
Traumatic brain injury
Zebrafish
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