Year: 2026
Type: article
Study design: Study Protocol
Abstract: Traumatic brain injury (TBI) remains a major global health concern with millions of people affected every year. The most critical long-term consequences of its presence are neuroinflammation and neurodegeneration, which are conditions that have been associated with protein aggregation, such as the accumulation of beta-amyloid plaques and tau tangles. Our proposal is intended to contribute to the knowledge of how TBI results in increased levels of Interleukin-6 (IL-6) in the brain and its function in neuroinflammation and protein aggregation, both of which are critical in neurodegenerative diseases. However, most existing studies examine IL-6 as a peripheral biomarker, and focus on its early prognostic value after TBI, without resolving how its context-dependent actions translate into chronic neurodegeneration and protein aggregation in vivo. In particular, the IL-6-TNF-α crosstalk that shapes long-term microglial activation, tau and amyloid pathology, and brain structural remodeling remains poorly defined in mechanistic and animal models. Tumor necrosis factor-alpha (TNF-α) is a central upstream cytokine in the neuroinflammatory cascade and closely interacts with IL-6 signalling, which has been shown to influence microglial activation and excitotoxic damage. This study proposes to use genetically engineered tumor necrosis factor-alpha (TNF-α) male mice to model TBI, with three-dimensional immunohistochemistry (3D IHC) to analyze post-injury changes. Neuroinflammatory markers, protein aggregates and structural changes in the brain will be evaluated as well as cytokines in the blood and cerebrospinal fluid (CSF). The expected outcome of this study is to identify molecular signatures of neurodegeneration, which may open new avenues for diagnosis and treatment of TBI patients. The findings will also be highly useful in understanding the long-term effects of TBI and its role in the onset of chronic diseases such as Alzheimer’s and Parkinson’s disease.
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7219984406