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Review
. 2024 Feb 17;25(4):2372.
doi: 10.3390/ijms25042372.

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets

Serena Silvestro  1 , Ivana Raffaele  1 , Angelo Quartarone  1 , Emanuela Mazzon  1
Affiliations
Review

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets

Serena Silvestro et al. Int J Mol Sci. .

Abstract

A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life and functionality. They cause two types of damage to the brain: primary and secondary. Secondary damage is particularly critical as it involves complex processes unfolding after the initial injury. These processes can lead to cell damage and death in the brain. Understanding how these processes damage the brain is crucial for finding new treatments. This review examines a wide range of literature from 2021 to 2023, focusing on biomarkers and molecular mechanisms in TBIs to pinpoint therapeutic advancements. Baseline levels of biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) in TBI, have demonstrated prognostic value for cognitive outcomes, laying the groundwork for personalized treatment strategies. In terms of pharmacological progress, the most promising approaches currently target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce a TBI's impact and aid in neurological rehabilitation. Future research is poised to refine these therapeutic approaches, potentially revolutionizing TBI treatment.

Keywords: molecular mechanisms; neuroprotection; physiological responses; regenerative medicine; rehabilitation; traumatic brain injury.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
In this image, the main types of TBI biomarkers are represented, highlighting the molecular processes in which they are involved, such as neuronal damage, glial damage, axonal damage, and inflammation. Specifically, NSE, SBP, UCH-L1, and EPB41 are biomarkers linked to neuronal cell body lesions. S100-B and GFAP are injury biomarkers of astroglial cells. Post-TBI astrogliosis and neuroinflammation can cause an increase in the production of interleukins and cytokines (IL-6, IL-10, and TNF-α), which can therefore be considered TBI biomarkers. NFL, Tau protein, Brain-derived Tau, MBP, and SBDP are axonal injury biomarkers. Beta-synuclein and SNCA are blood biomarkers of synaptic damage. The image was created using the image bank of Servier Medical Art (available online: http://smart.servier.com/; accessed on 30 December 2023) licensed under a Creative Commons Attribution 3.0 Unported License (available online: https://creativecommons.org/licenses/by/3.0/; accessed on 30 December 2023). Aβ: amyloid beta; EPAB41: erythrocyte membrane protein band 4.1; EVs: extracellular vesicles; GFAP: glial fibrillary acidic protein; IL-10: interleukin-10; IL-6: interleukin-6; NF-L: neurofilament light chain polypeptide; NSE: neuron-specific enolase; S100B: sport-related concussion calcium-binding protein B; SBDP: spectrin breakdown product; SNCA: alpha-synuclein; TBI: traumatic brain injury; TNF-α: tumor necrosis factor-alpha; UCH-L1: ubiquitin C-terminal hydrolase-L1; and VEGF: vascular endothelial growth factor.
Figure 2
Figure 2
Pathological changes associated with TBIs begin with a direct physical injury, known as a primary injury, which disrupts the BBB, damages axons, and activates glial cells. Subsequently, DAMPs released from injured cells can overactivate immune cells, leading to an increased production of pro-inflammatory factors that amplify the inflammatory response, thereby worsening the injury. Additionally, iron accumulation exacerbates oxidative stress and facilitates ferroptosis. At the same time, the excessive neuronal release of glutamate post-TBI lead to hyper stimulate glutamate receptors, increasing the influx of calcium and resulting in excitotoxicity. These interconnected processes significantly contribute to the secondary injury phase, potentially contributing to the cellular death in the brain and to neurological impairments. This image was created using the image bank of Servier Medical Art (Available online: http://smart.servier.com/; accessed on 30 December 2023) licensed under a Creative Commons Attribution 3.0 Unported License (available online: https://creativecommons.org/licenses/by/3.0/, accessed on 30 December 2023). BBB: blood–brain barrier; Ca2+: calcium; DAMP: damage-associated molecular pattern; HMGB1: High Mobility Group Box 1; IL-1β: interleukin-1 beta; IL-6: interleukin-6; iNOS: Inducible Nitric Oxide Synthase; NF-κB: nuclear factor-kappa B; NLRP3: NLR family pyrin domain containing 3; RNS: Reactive Nitrogen Species; ROS: reactive oxygen species; TBI: traumatic brain injury; and TNF-α: tumor necrosis factor-alpha.
Figure 3
Figure 3
Regenerative medicine. MSCs secrete biologically active molecules that can influence various molecular pathways. These treatments support the survival and proliferation of regional cells by secreting chemokines and growth factors. A significant aspect of their function is the reduction in edema and inflammation caused by injury, enhancing the secretion of anti-inflammatory cytokines while simultaneously reducing the secretion of pro-inflammatory cytokines. These multifaceted approaches highlight their significant impact in facilitating recovery from TBI, highlighting their ability to support tissue repair, mitigate inflammation, and promote neural regeneration. The image was created using the image bank of Servier Medical Art (available online: http://smart.servier.com/; accessed on 30 December 2023) licensed under a Creative Commons Attribution 3.0 Unported License (available online: https://creativecommons.org/licenses/by/3.0/; accessed on 15 December 2023). BBB: blood–brain barrier; MSCs: mesenchymal stem cells; ROS: reactive oxygen species; and TBI: traumatic brain injury.
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References

    1. McKee A.C., Daneshvar D.H. The neuropathology of traumatic brain injury. Handb. Clin. Neurol. 2015;127:45–66. - PMC - PubMed
    1. Wang K., Cui D., Gao L. Traumatic brain injury: A review of characteristics, molecular basis and management. Front. Biosci. Landmark. 2016;21:890–899. - PubMed
    1. Morrow S.E., Pearson M. Management Strategies for Severe Closed Head Injuries in Children. Elsevier; Amsterdam, The Netherlands: 2010. pp. 279–285. Seminars in Pediatric Surgery. - PubMed
    1. Mioni G., Grondin S., Stablum F. Temporal dysfunction in traumatic brain injury patients: Primary or secondary impairment? Front. Hum. Neurosci. 2014;8:269. doi: 10.3389/fnhum.2014.00269. - DOI - PMC - PubMed
    1. Abdul-Muneer P., Chandra N., Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol. Neurobiol. 2015;51:966–979. doi: 10.1007/s12035-014-8752-3. - DOI - PMC - PubMed

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