Pathophysiology-Based Management of Secondary Injuries and Insults in TBI

de Macedo Filho, Leonardo; Figueredo, Luisa F.; Villegas-Gomez, Gustavo Adolfo; Arthur, Matthew; Pedraza-Ciro, Maria Camila; Martins, Henrique; Kanawati Neto, Joaquim; Hawryluk, Gregory J.; Amorim, Robson Luís Oliveira

doi:10.3390/biomedicines12030520

Cited by 4 publications

(2 citation statements)

References 131 publications

(213 reference statements)

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“…Altogether, the present findings highlight the potential of blood-brain barrier-derived biomarkers to also assess and monitor the clinical course of traumatic brain injuries in humans. Specifically, we here addressed the diffuse secondary disease progression of acceleration/deceleration injuries that is particularly difficult to capture [58]. Currently, blood-based biomarkers reflecting neuronal (i.e., ubiquitin carboxy-terminal hydrolase L1, UCH-L1) or astrocyte (i.e., glial fibrillary acidic protein, GFAP) have emerged, mostly differentiating more severe forms of TBI, but not (mild) concussion [59].…”

Section: Discussionmentioning

confidence: 99%

Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice

Blaschke,

Rautenberg,

Endepols

et al. 2024

IJMS

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Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood–brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.

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Section: Discussionmentioning

confidence: 99%

Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice

Blaschke,

Rautenberg,

Endepols

et al. 2024

IJMS

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“…The pathophysiology of TBI has traditionally been divided into a primary injury and a secondary injury. The primary injury is caused by external direct mechanical insult, acceleration or deceleration forces, or penetrating objects causing focal and/or diffuse brain injury, including contusions, hemorrhages, and axonal injury ( de Macedo et al, 2024 ). Following primary injury to the brain, activation of a highly complex cascade of secondary events evolves simultaneously and interact to aggravate the primary brain injury ( Ng and Lee, 2019 ).…”

Section: The Pathophysiology Of Traumatic Brain Injurymentioning

confidence: 99%

Water channels in the brain and spinal cord—overview of the role of aquaporins in traumatic brain injury and traumatic spinal cord injury

Overgaard Wichmann,

Hedegaard Højsager,

Hasager Damkier

2024

Front. Cell. Neurosci.

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Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field.

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How to Define and Meet Blood Pressure Targets After Traumatic Brain Injury: A Narrative Review

Kartal,

Robba,

Helmy

et al. 2024

Neurocrit Care

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Background Traumatic brain injury (TBI) poses a significant challenge to healthcare providers, necessitating meticulous management of hemodynamic parameters to optimize patient outcomes. This article delves into the critical task of defining and meeting continuous arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) targets in the context of severe TBI in neurocritical care settings. Methods We narratively reviewed existing literature, clinical guidelines, and emerging technologies to propose a comprehensive approach that integrates real-time monitoring, individualized cerebral perfusion target setting, and dynamic interventions. Results Our findings emphasize the need for personalized hemodynamic management, considering the heterogeneity of patients with TBI and the evolving nature of their condition. We describe the latest advancements in monitoring technologies, such as autoregulation-guided ABP/CPP treatment, which enable a more nuanced understanding of cerebral perfusion dynamics. By incorporating these tools into a proactive monitoring strategy, clinicians can tailor interventions to optimize ABP/CPP and mitigate secondary brain injury. Discussion Challenges in this field include the lack of standardized protocols for interpreting multimodal neuromonitoring data, potential variability in clinical decision-making, understanding the role of cardiac output, and the need for specialized expertise and customized software to have individualized ABP/CPP targets regularly available. The patient outcome benefit of monitoring-guided ABP/CPP target definitions still needs to be proven in patients with TBI. Conclusions We recommend that the TBI community take proactive steps to translate the potential benefits of personalized ABP/CPP targets, which have been implemented in certain centers, into a standardized and clinically validated reality through randomized controlled trials.

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Pathophysiology-Based Management of Secondary Injuries and Insults in TBI

Cited by 4 publications

References 131 publications

Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice

Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice

Water channels in the brain and spinal cord—overview of the role of aquaporins in traumatic brain injury and traumatic spinal cord injury

How to Define and Meet Blood Pressure Targets After Traumatic Brain Injury: A Narrative Review

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