Differential Disruption of Blood–Brain Barrier in Severe Traumatic Brain Injury

Saw, Melanie M.; Chamberlain, Jenny; Barr, Michelle; Morgan, Matt; Burnett, John R.; Ho, Kwok M.

doi:10.1007/s12028-013-9933-z

Cited by 42 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with observations in animal models, evidence of acute BBB permeability following severe TBI in humans is provided by reports of elevations in CSF to serum albumin quotient (50)(51)(52)(53) and in serum S100² levels (50-53) after injury. Of note, such evidence of acute BBB disruption following TBI might predict a population of patients with poor longterm outcome (52).…”

Section: Page 4 Of 22supporting

confidence: 65%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Page 4 Of 22supporting

confidence: 65%

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

View full text Add to dashboard Cite

show abstract

“…15,16 In this study, we defined BBB disruption as a total CSF protein concentration to total plasma protein concentration ratio greater than 0.007, which correlates well with the traditional biochemical marker of BBB disruption (CSF-plasma albumin quotient [correlation coefficient 0.97]). 34 Because the BBB can be disrupted across a continuum of severity, we also assessed the prognostic significance of BBB disruption by analyzing the ratio of the total CSF protein concentrations to total plasma protein concentrations as a continuous variable. When more than 1 sample of CSF was obtained from the same patient, we analyzed the first sample collected after TBI.…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of blood-brain barrier disruption in patients with severe nonpenetrating traumatic brain injury requiring decompressive craniectomy

Honeybul

Yip

et al. 2014

JNS

Self Cite

View full text Add to dashboard Cite

Object The authors assessed the risk factors and outcomes associated with blood-brain barrier (BBB) disruption in patients with severe, nonpenetrating, traumatic brain injury (TBI) requiring decompressive craniectomy. Methods At 2 major neurotrauma centers in Western Australia, a retrospective cohort study was conducted among 97 adult neurotrauma patients who required an external ventricular drain (EVD) and decompressive craniectomy during 2004–2012. Glasgow Outcome Scale scores were used to assess neurological outcomes. Logistic regression was used to identify factors associated with BBB disruption, defined by a ratio of total CSF protein concentrations to total plasma protein concentration > 0.007 in the earliest CSF specimen collected after TBI. Results Of the 252 patients who required decompressive craniectomy, 97 (39%) required an EVD to control intracranial pressure, and biochemical evidence of BBB disruption was observed in 43 (44%). Presence of disruption was associated with more severe TBI (median predicted risk for unfavorable outcome 75% vs 63%, respectively; p = 0.001) and with worse outcomes at 6, 12, and 18 months than was absence of BBB disruption (72% vs 37% unfavorable outcomes, respectively; p = 0.015). The only risk factor significantly associated with increased risk for BBB disruption was presence of nonevacuated intracerebral hematoma (> 1 cm diameter) (OR 3.03, 95% CI 1.23–7.50; p = 0.016). Although BBB disruption was associated with more severe TBI and worse long-term outcomes, when combined with the prognostic information contained in the Corticosteroid Randomization after Significant Head Injury (CRASH) prognostic model, it did not seem to add significant prognostic value (area under the receiver operating characteristic curve 0.855 vs 0.864, respectively; p = 0.453). Conclusions Biochemical evidence of BBB disruption after severe nonpenetrating TBI was common, especially among patients with large intracerebral hematomas. Disruption of the BBB was associated with more severe TBI and worse long-term outcomes, but when combined with the prognostic information contained in the CRASH prognostic model, this information did not add significant prognostic value.

show abstract

“…Effectiveness of osmotic therapy depends on an intact blood-brain barrier. In a small study, more than one-third of patients treated with hypertonic saline had an impairment of passive blood brain barrier function, a higher ICP, and a trend toward increased mortality [67]. Continuous application of half-molar sodium lactate after TBI for 48 h reduced episodes of increased ICP and reduced fluid and chloride load [68,69].…”

Section: Traumatic Brain Injurymentioning

confidence: 99%