Rapid Loss of Microvascular Integrin Expression during Focal Brain Ischemia Reflects Neuron Injury

Tagaya, Masayoshi; Haring, Hans‐Peter; Stuiver, Ingrid; Wagner, Simone; Abumiya, Takeo; Lucero, Jacinta; Lee, Pauline; Copeland, Brian R.; Seiffert, Dietmar; Zoppo, Gregory J. del

doi:10.1097/00004647-200107000-00009

Cited by 134 publications

(159 citation statements)

References 69 publications

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“…Microvessel adhesion receptor and basal lamina matrix expression can present as 'mini-cores' and 'mini-penumbras' within the early evolving core of neuron injury, after occlusion of a brain-supplying artery, in a characteristic time-dependent manner (Tagaya et al, 2001). Given that the microvasculature, which in capillaries consists of the endotheliumbasal lamina matrix-astrocyte end-feet complex, serves neurons (as part of a hypothetical 'neurovascular unit'), changes in microvessels and neurons must to be connected locally.…”

Section: Evolving Definitions Of the Penumbramentioning

confidence: 99%

Heterogeneity in the penumbra

Zoppo

Sharp

Heiss

et al. 2011

J Cereb Blood Flow Metab

146

120

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Original experimental studies in nonhuman primate models of focal ischemia showed flow-related changes in evoked potentials that suggested a circumferential zone of low regional cerebral blood flow with normal K + homeostasis, around a core of permanent injury in the striatum or the cortex. This became the basis for the definition of the ischemic penumbra. Imaging techniques of the time suggested a homogeneous core of injury, while positing a surrounding 'penumbral' region that could be salvaged. However, both molecular studies and observations of vascular integrity indicate a more complex and dynamic situation in the ischemic core that also changes with time. The microvascular, cellular, and molecular events in the acute setting are compatible with heterogeneity of the injury within the injury center, which at early time points can be described as multiple 'minicores' associated with multiple 'mini-penumbras'. These observations suggest the progression of injury from many small foci to a homogeneous defect over time after the onset of ischemia. Recent observations with updated imaging techniques and data processing support these dynamic changes within the core and the penumbra in humans following focal ischemia.

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Section: Evolving Definitions Of the Penumbramentioning

confidence: 99%

Heterogeneity in the penumbra

Zoppo

Sharp

Heiss

et al. 2011

J Cereb Blood Flow Metab

146

120

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“…Focal cerebral ischemia causes a significant and rapid decrease in microvessel-associated b 1 -integrin immunoreactivity in concert with increased barrier permeability (Haring et al, 1996;Tagaya et al, 1997Tagaya et al, , 2001. To test whether the blockade of b 1 -integrin function alters blood-brain barrier integrity in situ, the impact at 24 hours of Ha2/5 or isotype stereotaxically delivered antibodies into the striatum of mice on normal cerebral vascular impermeability (i.e., no IgG extravasation) was quantified.…”

Section: Effect Of B 1 -Integrin Blockade On Permeability Barrier Intmentioning

confidence: 99%

“…In adult brain, endothelial cells express b 1 -integrins in all microvessel diameter classes (Haring et al, 1996). And, b 1 -integrins interact with the ECM proteins laminin, collagen type IV, and perlecan, found in the basal lamina of all central nervous system microvessels (Haring et al, 1996;Tagaya et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies imply that b 1 -integrins expressed by endothelial cells, among other matrix adhesion receptors, could have important roles in maintaining the permeability barrier ('vertical' adhesion) (del Zoppo and Milner, 2006). The rapidity of the loss of b 1 -integrin immunoreactivity in the ischemic core following middle cerebral artery occlusion (Tagaya et al, 2001) and its temporal relation to edema suggest that b 1 -integrin-dependent adhesion could be relevant to permeability barrier integrity. However, during focal ischemia endothelial cell demise is infrequent, suggesting the stability of endothelial cell-matrix adhesion (Tagaya et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins

Osada

Kanazawa

et al. 2011

J Cereb Blood Flow Metab

128

120

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The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by b 1 -integrin receptors expressed by endothelial cells have an important role in maintaining the cerebral microvessel permeability barrier. Primary brain endothelial cells from C57 BL/6 mice were incubated with b 1 -integrin function-blocking antibody (Ha2/5) or isotype control and the impacts on claudin-5 expression and microvessel permeability were quantified. Both flow cytometry and immunofluorescence studies demonstrated that the interendothelial claudin-5 expression by confluent endothelial cells was significantly decreased in a time-dependent manner by Ha2/5 exposure relative to isotype. Furthermore, to assess the barrier properties, transendothelial electrical resistance and permeability measurements of the monolayer, and stereotaxic injection into the striatum of mice were performed. Ha2/5 incubation reduced the resistance of endothelial cell monolayers significantly, and significantly increased permeability to 40 and 150 kDa dextrans. Ha2/5 injection into mouse striatum produced significantly greater IgG extravasation than the isotype or the control injections. This study demonstrates that blockade of b 1 -integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell-matrix interactions via b 1 -integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability.

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“…Effect of focal cerebral ischemia on microvascular matrix adhesion receptor expression. Immunoreactivity of select integrin receptors on endothelial cells and astrocyte end-feet is significantly reduced within 2 hours of middle cerebral artery occlusion (see 75,86 ). Note increase in expression of integrin ␣ v ␤ 3 (inset).…”

Section: Multiple Sclerosis and Experimental Autoimmune Encephalomyelmentioning

confidence: 99%

Cerebral Microvasculature

2011

Encyclopedia of Clinical Neuropsychology

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Abstract-The integrity of all organ systems requires faithful interaction between its component cells and the extracellular matrix (ECM). In the central nervous system (CNS), matrix adhesion receptors are uniquely expressed by the cells comprising the microvascular compartment, and by neurons and their supporting glial cells. Cells within the cerebral microvasculature express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Capillaries of the cerebral microvasculature consist of the luminal endothelium, which is separated from circumferential astrocyte end-feet by the intervening ECM of the basal lamina. Endothelial cells and astrocytes cooperate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells, and oligodendroglia. Significant alterations in both cellular adhesion receptors and their ligands occur under the conditions of focal cerebral ischemia, multiple sclerosis (MS) and the modeled condition experimental autoimmune encephalomyelitis (EAE), certain tumors of the CNS, and arteriovenous malformations (AVMs). The changes in matrix adhesion receptor expression in these conditions support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood-brain permeability barrier, and that modulation of these receptors contribute to alterations in the barrier during brain injury. This review examines current information about cell adhesion receptor expression within the cerebral microvasculature and surrounding tissue, and their potential roles during the vascular responses to local injury. T he cerebral microvasculature is unique in that while serving as a conduit for supplying blood-to-brain structures, it is also completely incorporated within the neuropil, allowing direct interactions with glia and neurons. The cerebral microvasculature is also functionally dynamic. It maintains and with states of arousal and neuronal activation increases local and regional blood flow to provide cellular nutritional support. 1-4 Both local and distant control of cerebral blood flow during activation results from neuronvascular coupling via astrocytes, and from direct innervation. 1,2 The close proximity between the endothelium and astrocyte end-feet of intact cerebral capillaries also implies potential communication between the cells across the basal lamina.Pial and cortical penetrating arteries consist of an endothelial cell layer, the basal lamina (derived from the extracellular matrix [ECM]), a myointima with smooth muscle cells encased in the matrix, and an adventitia. 5 Arising from the leptomeninges, the adventitia of th...

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Rapid Loss of Microvascular Integrin Expression during Focal Brain Ischemia Reflects Neuron Injury

Cited by 134 publications

References 69 publications

Heterogeneity in the penumbra

Heterogeneity in the penumbra

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins

Cerebral Microvasculature

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Rapid Loss of Microvascular Integrin Expression during Focal Brain Ischemia Reflects Neuron Injury

Cited by 134 publications

References 69 publications

Heterogeneity in the penumbra

Heterogeneity in the penumbra

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β1-Integrins

Cerebral Microvasculature

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Resources

About

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins