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

Document Type : Original Article

Authors

Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Chennai-600116, Tamil Nadu, India

10.22038/ijbms.2026.90876.19603

Abstract

Background: 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. The cascade of TBI and its secondary complications exacerbates neuronal damage, culminating in cellular demise. Pathophysiological mechanisms encompass mitochondrial dysfunction, heightened free radical activity, neuroinflammation-mediated myelin degradation, and neuronal necrosis, further compounded by metabolic dysregulation stemming from DNA damage or mutation induced by protein aggregation. Microenvironmental constituents and signalling pathways intricately contribute to the progression of neurological sequelae following TBI, frequently characterized by edema and blood-brain barrier disruption, facilitating blood infiltration into the surrounding tissues. Limonin, a secondary metabolite renowned for its mitigation of metabolic syndrome risk factors, notably cardiovascular complications and fatty liver disease, demonstrates promising neuroprotective properties in-vitro.
Results: This study aimed to elucidate the in-vivo neuromodulatory effects of limonin using an adult Zebrafish model. Limonin treatment exhibited a remarkable reduction in anxiety levels. Through a series of assays encompassing behaviour, histological, and biochemical analyses, adjacent rescue from cell death despite a native regenerative background of a wildtype Zebrafish was seen. Lipid peroxidation induced neuroinflammation and timely resolution in comparison with TBI control were observed with 300 µM Limonin treatment. A novel brain cell suspension from Adult Zebrafish was also employed to discover rescue against necrotic cell death cues.
Conclusion: These findings underscore the potential of limonin as a potent neuromodulator, warranting further preclinical investigations in mitigating TBI-associated neurological deficits.

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References

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Iranian Journal of Basic Medical Sciences
Volume 29, Issue 3
March 2026
Pages 468-481

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