Background
Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often
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.
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.