The glymphatic system’s role in traumatic brain injury-related neurodegeneration

Peters, Matthew E.

doi:10.1038/s41380-023-02070-7

Cited by 16 publications

(4 citation statements)

References 120 publications

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Section: Introductionmentioning

confidence: 66%

“…Notably, experimental TBI has been shown to cause a 60% reduction in glymphatic flow, which persists for over a month 22 . Additional evidence from animal studies also supports the idea that glymphatic dysfunction contributes to subsequent neurodegeneration and cognitive decline 17,23 . Imaging the glymphatic system directly in humans poses significant challenges due to the necessity of intrathecally injecting gadolinium (Gd)-based contrast agents as CSF tracers to track their passage through the glymphatic system 24,25 .…”

Section: Introductionmentioning

confidence: 68%

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Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging

Zhuo,

Raghavan,

Jiang

et al. 2024

Preprint

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AbstractsTraumatic brain injury (TBI) even in the mild form may result in long-lasting post- concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM- ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post- concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

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Section: Introductionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 68%

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging

Zhuo,

Raghavan,

Jiang

et al. 2024

Preprint

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“…The emerging studies linking TBI, glymphatic disruption, sleep and risk of neurodegenerative disorders support a complex dynamic association between specific trauma induced physiological perturbation and chronic neuropathological changes. Hence the glymphatic system integrity and functioning post-injury would likely serve as a robust biomarker of TBI severity and a predictive marker for potential neurodegenerative sequelae (Peters and Lyketsos, 2023).…”

Section: Glymphatic System Disruptionmentioning

confidence: 99%

An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms

Fesharaki-Zadeh,

Datta

2024

Front. Cell. Neurosci.

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BackgroundTraumatic brain injury (TBI) is a major cause of morbidity and mortality, affecting millions annually worldwide. Although the majority of TBI patients return to premorbid baseline, a subset of patient can develop persistent and often debilitating neurocognitive and behavioral changes. The etiology of TBI within the clinical setting is inherently heterogenous, ranging from sport related injuries, fall related injuries and motor vehicle accidents in the civilian setting, to blast injuries in the military setting.ObjectiveAnimal models of TBI, offer the distinct advantage of controlling for injury modality, duration and severity. Furthermore, preclinical models of TBI have provided the necessary temporal opportunity to study the chronic neuropathological sequelae of TBI, including neurodegenerative sequelae such as tauopathy and neuroinflammation within the finite experimental timeline. Despite the high prevalence of TBI, there are currently no disease modifying regimen for TBI, and the current clinical treatments remain largely symptom based. The preclinical models have provided the necessary biological substrate to examine the disease modifying effect of various pharmacological agents and have imperative translational value.MethodsThe current review will include a comprehensive survey of well-established preclinical models, including classic preclinical models including weight drop, blast injury, fluid percussion injury, controlled cortical impact injury, as well as more novel injury models including closed-head impact model of engineered rotational acceleration (CHIMERA) models and closed-head projectile concussive impact model (PCI). In addition to rodent preclinical models, the review will include an overview of other species including large animal models and Drosophila.ResultsThere are major neuropathological perturbations post TBI captured in various preclinical models, which include neuroinflammation, calcium dysregulation, tauopathy, mitochondrial dysfunction and oxidative stress, axonopathy, as well as glymphatic system disruption.ConclusionThe preclinical models of TBI continue to offer valuable translational insight, as well as essential neurobiological basis to examine specific disease modifying therapeutic regimen.

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“…Additionally, the glymphatic system is compromised post-TBI. This disruption might facilitate protein buildup, paving the way for neurodegeneration [ 130 ].…”

Section: Potential Role Of Astrocytes In Sleep Disorders Comorbiditiesmentioning

confidence: 99%

Exploring Astrocyte-Mediated Mechanisms in Sleep Disorders and Comorbidity

Li,

Que,

Wang

et al. 2023

Biomedicines

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Astrocytes, the most abundant cells in the brain, are integral to sleep regulation. In the context of a healthy neural environment, these glial cells exert a profound influence on the sleep-wake cycle, modulating both rapid eye movement (REM) and non-REM sleep phases. However, emerging literature underscores perturbations in astrocytic function as potential etiological factors in sleep disorders, either as protopathy or comorbidity. As known, sleep disorders significantly increase the risk of neurodegenerative, cardiovascular, metabolic, or psychiatric diseases. Meanwhile, sleep disorders are commonly screened as comorbidities in various neurodegenerative diseases, epilepsy, and others. Building on existing research that examines the role of astrocytes in sleep disorders, this review aims to elucidate the potential mechanisms by which astrocytes influence sleep regulation and contribute to sleep disorders in the varied settings of brain diseases. The review emphasizes the significance of astrocyte-mediated mechanisms in sleep disorders and their associated comorbidities, highlighting the need for further research.

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The glymphatic system’s role in traumatic brain injury-related neurodegeneration

Cited by 16 publications

References 120 publications

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging

An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms

Exploring Astrocyte-Mediated Mechanisms in Sleep Disorders and Comorbidity

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