Archives of Trauma Research (Jun 2024)
MicroRNA biomarkers for predicting neurological outcomes in traumatic brain injury patients
Abstract
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, characterized by a complex cascade of pathophysiological events that can result in diverse clinical outcomes ranging from mild cognitive impairments to severe disability. The pathophysiology of TBI involves a complex interplay of cellular and molecular events that contribute to secondary brain injury and neurodegeneration. Predicting neurological outcomes in TBI patients is crucial for guiding treatment decisions and enhancing patient care. Traditional methods of assessing TBI severity and prognosis have limitations in accurately predicting long-term outcomes. In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for evaluating TBI severity and prognosis. MicroRNAs are small non-coding RNA molecules that regulate gene expression and have been implicated in various physiological and pathological processes, including neurodevelopment, neuronal function, and neurodegeneration. Several studies have identified specific miRNAs as potential biomarkers for assessing TBI severity and predicting patient outcomes. MiR-21, miR-155, miR-146a, and miR-124 are among the most studied miRNAs in the context of TBI biomarkers. Elevated levels of these miRNAs in blood, cerebrospinal fluid, and brain tissue have been associated with TBI severity, neuroinflammation, and poor neurological outcomes. Understanding the role of miRNAs in TBI pathophysiology can provide valuable insights into the mechanisms underlying neuroinflammation and neurodegeneration. Furthermore, miRNA signatures have shown promise in distinguishing between different TBI phenotypes, such as mild, moderate, and severe TBI, and predicting long-term cognitive deficits and functional impairments in TBI survivors. This suggests that miRNAs could serve as valuable tools for improving TBI patient care and outcomes.[1,2] Role of miRNAs in TBI PathophysiologyMicroRNAs play a crucial role in modulating neuroinflammatory responses and neurodegenerative processes in traumatic brain injury. Dysregulated expression of specific miRNAs contributes to secondary brain injury, neuronal apoptosis, neuroinflammation, blood-brain barrier disruption, neurodegeneration, and cognitive impairments following TBI.[2]Neuroinflammation is a hallmark feature of TBI, characterized by the activation of microglia, astrocytes, and peripheral immune cells in response to brain injury. Dysregulated expression of specific miRNAs has been implicated in modulating neuroinflammatory responses following TBI. For example, miR-155 has been shown to promote microglial activation and pro-inflammatory cytokine production, exacerbating neuroinflammation and neuronal damage. In contrast, miR-146a acts as a negative regulator of inflammatory signaling pathways, attenuating neuroinflammatory responses and promoting neuroprotection in TBI models. The dynamic interplay between miRNAs and inflammatory mediators in the injured brain highlights the intricate regulatory mechanisms underlying neuroinflammation in TBI.[3]Neuronal cell death and neurodegeneration are other common pathological features of TBI, contributing to long-term cognitive impairments and functional deficits. Dysregulated expression of miRNAs has been associated with apoptotic cell death, synaptic dysfunction, and axonal injury in TBI. MiR-21, for instance, has been shown to promote neuronal apoptosis and glial scar formation following brain injury, exacerbating neurodegenerative processes. In contrast, miR-124 plays a neuroprotective role by regulating neuronal differentiation, synaptic plasticity, and axonal regeneration in response to TBI. The complex interplay between miRNAs and neurodegenerative pathways underscores their potential as therapeutic targets for mitigating neuronal damage and promoting recovery after TBI.[3]Targeting dysregulated miRNAs represents a promising therapeutic strategy for modulating neuroinflammation and neurodegeneration in TBI. MiRNA-based interventions, such as antagomirs or mimics, offer potential avenues for restoring miRNA homeostasis and promoting neuroprotective effects in the injured brain. Future research efforts should focus on identifying specific miRNA targets involved in TBI pathophysiology, elucidating their functional roles in neuroinflammation and neurodegeneration, and exploring innovative therapeutic approaches for TBI management. Collaborative initiatives between researchers, clinicians, and pharmaceutical companies are essential for translating miRNA research into clinical applications and improving outcomes for TBI patients.[4] MiRNA Biomarkers for Predicting Neurological RecoveryThe utilization of miRNA biomarkers in clinical practice holds the potential to revolutionize prognostication and treatment decision-making in TBI. By pinpointing specific miRNA signatures linked to neurological outcomes, clinicians can categorize patients based on their likelihood of developing complications, cognitive impairments, or disability post-TBI. Numerous studies have documented distinct expression patterns of miRNAs in TBI patients with varying levels of cognitive impairment, functional disability, and neurobehavioral deficits. MiR-21, miR-146a, and miR-132 have emerged as promising biomarkers for forecasting neurological recovery and functional outcomes in TBI. The integration of miRNA profiles with clinical evaluations and neuroimaging data has the potential to enhance the precision of outcome predictions and facilitate personalized treatment approaches for TBI patients. Further research is imperative to validate miRNA signatures, establish standardized protocols for miRNA profiling, and implement predictive models that amalgamate clinical, imaging, and molecular data to enhance prognostication and treatment strategies for TBI patients. Future research endeavors should prioritize the validation of miRNA biomarkers in extensive prospective cohorts, elucidate their mechanistic roles in TBI pathophysiology, and incorporate them into multidimensional prognostic models for tailored patient care. Collaborative initiatives involving researchers, clinicians, and industry partners are paramount for translating miRNA research into clinical applications and enhancing outcomes for TBI patients.[5,6] Challenges and Opportunities for Advancing MiRNA Biomarker in TBIDespite the growing interest in miRNA biomarkers for TBI, several challenges need to be addressed before their clinical implementation. Standardization of sample collection and processing protocols, validation of miRNA signatures in large patient cohorts, and integration of miRNA data with other clinical variables are critical steps towards translating miRNA research into clinical practice. Additionally, the lack of standardized protocols for miRNA profiling and validation poses obstacles to comparing results across different studies. The heterogeneity of TBI phenotypes and patient populations further complicates the identification of robust miRNA signatures predictive of neurological outcomes.[4,5] Despite the challenges, there are promising opportunities for advancing miRNA biomarker research in TBI. Technological advancements in high-throughput sequencing and bioinformatics tools enable comprehensive profiling of miRNA expression patterns in TBI patients. Collaborative efforts among researchers, clinicians, and industry partners can facilitate the validation of miRNA biomarkers in large multicenter cohorts, enhancing their clinical utility. Integrating miRNA profiles with other omics data, neuroimaging findings, and clinical assessments holds potential for developing multidimensional prognostic models for personalized TBI management.[6] ConclusionFuture research directions should focus on standardizing methodologies for miRNA biomarker discovery, validation, and implementation in TBI clinical practice. Large-scale prospective studies are needed to validate miRNA signatures associated with specific TBI outcomes and refine predictive models for patient stratification. Incorporating miRNA biomarkers into existing prognostic tools and treatment algorithms may improve risk assessment, therapeutic decision-making, and long-term outcomes for TBI patients. Collaborative initiatives aimed at translating miRNA research findings into actionable clinical insights are essential for realizing the full potential of miRNA biomarkers in TBI management.
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