Vascular permeability alterations to horseradish peroxidase in experimental brain injury

Povlishock, John T.; Becker, Donald P.; Sullivan, Humbert G.; Miller, J. D.

doi:10.1016/0006-8993(78)90404-3

“…As regards possible structural correlates of this acute BBB disruption, ultrastructural studies in animal models of TBI have identified a variety of alterations in vascular endothelia in the Page 14 of 22 acute phase following injury, including the formation of vacuoles, craters and microvilli (47,(57)(58)(59) some of which were later identified in human TBI (60,61). These very rapid changes in vascular structure and function have been attributed to a range of mechanisms such as direct perturbation of the vessels by mechanical forces, including the immediate disruption of vascular endothelial cells.…”

Section: Discussionmentioning

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

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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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“…Additional, secondary insults following injury might also be detrimental to normal endothelial integrity and function, including acute rises in arterial pressure or intravascular thrombus formation (45,56,57). Finally, active physiological changes have also been described in both animals and humans following TBI, including increased transendothelial vesicular transport with otherwise intact tight junctions (47,59,61,62) as well as alterations to other components of the BBB, such as early astrocyte disruption and swelling (45,58).…”

Section: Discussionmentioning

confidence: 99%

“…Following TBI, acute phase BBB disruption has been demonstrated in several animal models (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) though with conflicting data on the time-course of this disruption some studies suggesting BBB disruption is short lived, resolving within hours of injury (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47), while others suggest a more dynamic, biphasic course following injury, with early phase BBB disruption at 3-6 hours post injury followed by later, further BBB at 1-3 (38,48). In support of this 'late' BBB dysregulation after TBI is the observation of focal immunoglobulin G (IgG)…”

Section: Introductionmentioning

confidence: 99%

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

Hay

¹

,

Johnson

²

,

Young

³

et al. 2015

Journal of Neuropathology & Experimental Neurology

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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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“…Areas of BBB breakdown can be associated with contusion formation in both gray and white matter areas. Also, brainstem nuclei appear to be susceptible to head trauma, in terms of permeability abnormalities (Povlishock et al, 1978). In both cerebral ischemia and trauma, abnormalities in vascular permeability participate in the early pathogenesis of these insults (Povlishock and Dietrich, 1992).…”

Section: Figmentioning

confidence: 99%

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Bramlett

¹

,

Dietrich

²

2004

J Cereb Blood Flow Metab

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Summary: Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes. Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead to metabolic stress, ionic perturbations, and a complex cascade of biochemical and molecular events ultimately causing neuronal death. Similarities in the pathogenesis of these cerebral injuries may indicate that therapeutic strategies protective following ischemia may also be beneficial after trauma. This review summarizes and contrasts injury mechanisms after ischemia and trauma and discusses neuroprotective strategies that target both types of injuries.

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Vascular permeability alterations to horseradish peroxidase in experimental brain injury

Cited by 209 publications

References 31 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

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

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

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