Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Alejandro; Friedman, Alon; Shelef, Ilan

doi:10.1155/2011/765923

Cited by 174 publications

(146 citation statements)

References 41 publications

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“…Of note, such evidence of acute BBB disruption following TBI might predict a population of patients with poor longterm outcome (52). Furthermore, neuroimaging evidence of BBB disruption has been reported in patients following TBI, even after clinically mild or moderate injury; in some cases persisting for years at the site of focal injury (contusions) and with greater frequency in patients with post-traumatic epilepsy (54). Intriguingly, imaging evidence of BBB disruption has been observed in American football participants, independent of clinical evidence of TBI, possibly as a result of exposure to 'sub-concussive' head impacts(55).…”

Section: Page 4 Of 22mentioning

confidence: 99%

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

Hay¹,

Johnson²,

Young³

et al. 2015

J Neuropathol Exp Neurol

115

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Traumatic brain injury (TBI) is a risk factor for dementia, with studies describing a mixed neurodegenerative pathology in late survivors. However, the mechanisms driving this post-TBI neurodegeneration remain elusive. Increasingly, blood brain barrier (BBB) disruption is recognized in a range of neurological disorders, including dementias; although little is known of the consequences of TBI on the BBB. From the Glasgow TBI Archive autopsy cases of single, moderate or severe TBI (n=70) were selected to include a range of survivals from acute (10h to 13days) to long-term (1 to 47years) survival, together with age-matched, uninjured controls (n=21). Multiple brain regions were examined for fibrinogen (FBG) and immunoglobulin G (IgG) immunohistochemistry. Following TBI, 40% of patients dying in the acute phase and 47% of those surviving a year or more from injury showed multi-focal, abnormal, perivascular and parenchymal FBG and IgG immunostaining localized to grey matter, with preferential distribution towards the crests of gyri and deep neocortical layers. In contrast, where present, controls showed only limited, localized immunostaining. These preliminary data demonstrate evidence of widespread BBB disruption in a proportion of TBI patients emerging in the acute phase and, intriguingly, persisting in a high proportion of late survivors.

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Section: Page 4 Of 22mentioning

confidence: 99%

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

Hay¹,

Johnson²,

Young³

et al. 2015

J Neuropathol Exp Neurol

115

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“…Shlosberg and associates are of the view that because uncontrolled brain edema usually champions brain herniation which is the main causes of death in patients after TBI [35], early treatment with anti-HMGB1mAb might be a promising strategy for TBI and other complications such as post-traumatic epilepsy [49] and impairment in cognitive function [50]. Guo and colleagues have also indicated that TBI is a risk factor for Alzheimer disease [51].…”

Section: Therapeutic Potentials Hmgb1mentioning

confidence: 99%

High Mobility Group Box 1 and Traumatic Brain Injury

Richard¹,

Wu²,

Su³

et al. 2017

JBBS

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. We identify High Mobility Group Box 1 (HMGB1) as a novel causative factor in the development of cerebral oedema, mediating coagulation, preventing secondary brain damage as well as serving as a novel therapeutic target to limit secondary neurological injury after TBI. As a prototypical danger associated molecular patterns (DAMP), HMGB1 is released from necrotic neurons via a NR2B-mediated mechanism during TBI. The secretion of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response. HMGB1 is clinically associated with elevated intracranial pressure (ICP) in patients and functionally promoted cerebral edema after TBI. The detrimental effects of HMGB1 is mediated at least in part between activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel aquaporin-4 (AQP4). Anti-HMGB1mAb remarkably inhibited fluid percussion-induced brain edema by inhibiting HMGB1 translocation, protection of blood-brain barrier (BBB) integrity, suppression of inflammatory molecule expression and improvement of motor function. Our review demonstrates the pathological role of HMGB1 as well as the possible therapeutic valve of HMGB1 in patients with TBI.

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“…For the purposes of epilepsy surgery that may occur in the post-traumatic setting, EEG has been co-registered with fMRI for the purposes of improved localization of foci of seizure activity. EEG has also been used to examine TBI-related disruption of the blood-brain barrier (Korn et al, 2005;Tomkins et al, 2011).…”

Section: Other Techniquesmentioning

confidence: 99%

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

Hunter

Wilde

Tong

et al. 2012

Journal of Neurotrauma

114

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This article identifies emerging neuroimaging measures considered by the inter-agency Pediatric Traumatic Brain Injury (TBI) Neuroimaging Workgroup. This article attempts to address some of the potential uses of more advanced forms of imaging in TBI as well as highlight some of the current considerations and unresolved challenges of using them. We summarize emerging elements likely to gain more widespread use in the coming years, because of 1) their utility in diagnosis, prognosis, and understanding the natural course of degeneration or recovery following TBI, and potential for evaluating treatment strategies; 2) the ability of many centers to acquire these data with scanners and equipment that are readily available in existing clinical and research settings; and 3) advances in software that provide more automated, readily available, and cost-effective analysis methods for large scale data image analysis. These include multi-slice CT, volumetric MRI analysis, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), arterial spin tag labeling (ASL), functional MRI (fMRI), including resting state and connectivity MRI, MR spectroscopy (MRS), and hyperpolarization scanning. However, we also include brief introductions to other specialized forms of advanced imaging that currently do require specialized equipment, for example, single photon emission computed tomography (SPECT), positron emission tomography (PET), encephalography (EEG), and magnetoencephalography (MEG)/magnetic source imaging (MSI). Finally, we identify some of the challenges that users of the emerging imaging CDEs may wish to consider, including quality control, performing multi-site and longitudinal imaging studies, and MR scanning in infants and children.

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Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

Cited by 174 publications

References 41 publications

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans

High Mobility Group Box 1 and Traumatic Brain Injury

Emerging Imaging Tools for Use with Traumatic Brain Injury Research

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