The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

Hawkins, Brian T.; Davis, Thomas P.

doi:10.1124/pr.57.2.4

Cited by 2,217 publications

(1,818 citation statements)

References 191 publications

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“…Alterations in expression or location of these proteins have been correlated to decreased barrier function. Decreased occludin expression, such as seen in both the present and previous studies 72 h post-CFA treatment, will disrupt BBB function (Bolton et al, 1998;Brooks et al, 2005;Brown and Davis, 2005;Hawkins and Davis, 2005;Huber et al, 2002a). Similarly, modulation of JAM-1 protein expression and/or localization is linked to a decrease in normal barrier function, and increased paracellular transport (Dobrogowska and Vorbrodt, 2004;Liang et al, 2002;Mandell and Parkos, 2005).…”

Section: Discussionsupporting

confidence: 65%

“…While the claudins are critical for cell-cell adhesion, their function is dependent on the interaction with other TJ proteins (Bazzoni and Dejana, 2004;Hawkins and Davis, 2005;Huber et al, 2002a;Wolka et al, 2003). A disruption of TJ protein interactions may be responsible for the BBB integrity loss observed in this study, as opposed to changes in only a single protein.…”

Section: Discussionmentioning

confidence: 76%

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Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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The blood-brain barrier (BBB) is a dynamic system which maintains brain homeostasis and limits CNS penetration via interactions of transmembrane and intracellular proteins. Inflammatory pain (IP) is a condition underlying several diseases with known BBB perturbations, including stroke, Parkinson's, multiple sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we demonstrated alterations in BBB paracellular permeability with correlating changes in tight junction (TJ) proteins: occludin and claudin-5. The present study examines the IP-induced molecular changes leading to a loss in functional BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the right hindpaw of female Sprague-Dawley rats. Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability was assessed by in situ brain perfusion of [ 14 C]sucrose (paracellular diffusion marker). The permeability of the BBB was significantly increased at 24 and 72 h post-CFA. Analysis of the TJ proteins, which control the paracellular pathway, demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72 h post-injection. Occludin expression was significantly decreased 72 h post-CFA. Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5 expression was not limited to the junction. These results provide evidence that chronic IP causes dramatic alterations in specific cytoarchitectural proteins and demonstrate alterations in molecular properties during CFA, resulting in significant changes in BBB paracellular permeability.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 76%

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

et al. 2006

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“…The 'neurovascular unit' provides a conceptual framework that emphasizes cell-cell interactions between neuronal, glial, and vascular elements. [4][5][6][7][8][9][10] This concept primarily guides research in neuron-related cell-cell interaction mechanisms in gray matter. But cell-cell signaling between nonneuronal cells should also be critical for white-matter function.…”

Section: Introductionmentioning

confidence: 99%

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

Shindo

Liang

Maki

et al. 2015

J Cereb Blood Flow Metab

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Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

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“…[6][7][8][9][10] Studies in the mature brain have shown that the microvascular responses after ischemia are rapid and temporally linked to neuronal injury. 5,[11][12][13] Nitric oxide (NO) biosynthesis is a key factor in the pathophysiologic response to ischemia. 14 Ischemia causes neuronal membrane depolarization that leads to massive glutamate releases and overstimulation of N-methyl-D-aspartate receptors (NMDAR).…”

Section: Introductionmentioning

confidence: 99%

Cerebral Microvascular Damage Occurs Early after Hypoxia–Ischemia via nNOS Activation in the Neonatal Brain

Hsu

Chang

Lin

et al. 2014

J Cereb Blood Flow Metab

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Microvascular injury early after hypoxic ischemia (HI) may contribute to neonatal brain damage. N-methyl-D-aspartate receptor overstimulation activates neuronal nitric oxide synthases (nNOS). We hypothesized that microvascular damage occurs early post-HI via nNOS activation and contributes to brain injury. Postpartum day-7 rat pups were treated with 7-nitroindazole (7-NI) or aminoguanidine (AG) before or after HI. Electron microscopy was performed to measure neuronal and endothelial cell damage. There were vascular lumen narrowing at 1 hour, pyknotic neurons at 3 hours, and extensive neuronal damage and loss of vessels at 24 hours post HI. Early after reoxygenation, there were neurons with heterochromatic chromatin and endothelial cells with enlarged nuclei occluding the lumen. There was also increased 3-nitrotyrosin in the microvessels and decreased cerebral blood perfusion. 7-NI and AG treatment before hypoxia provided complete and partial neuroprotection, respectively. Early post-reoxygenation, the AG group showed significantly increased microvascular nitrosative stress, microvascular interruptions, swollen nuclei that narrowed the vascular lumen, and decreased cerebral perfusion. The 7-NI group showed significantly decreased microvascular nitrosative stress, patent vascular lumen, and increased cerebral perfusion. Our results indicate that microvascular damage occurs early and progressively post HI. Neuronal nitric oxide synthases activation contributes to microvascular damage and decreased cerebral perfusion early after reoxygenation and worsens brain damage.

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The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

Cited by 2,217 publications

References 191 publications

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

Cerebral Microvascular Damage Occurs Early after Hypoxia–Ischemia via nNOS Activation in the Neonatal Brain

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