Aberrant astrocytes impair vascular reactivity in <scp>H</scp>untington disease

Hsiao, Han-Yun; Chen, Yu‐Chen; Huang, Chien-Hsiang; Chen, Chiao-Chi; Hsu, Yi-Hua; Chen, Huimei; Chiu, Feng‐Lan; Kuo, Hung‐Chih; Chang, Chen; Chern, Yijuang

doi:10.1002/ana.24428

Cited by 79 publications

(69 citation statements)

References 45 publications

(127 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The association between astrocytes and BV after retinal injury could have important physiological consequences. Indeed, in an animal model of Huntington’s disease astrocytes promote angiogenesis and reduce the number of pericytes associated with BV by an increased production of vascular endotheial growth factor (A) and IkB (Hsiao et al, 2015)…”

Section: Resultsmentioning

confidence: 99%

Astrocyte structural reactivity and plasticity in models of retinal detachment

Luna

Keeley

Reese

et al. 2016

Experimental Eye Research

View full text Add to dashboard Cite

Although retinal neurodegenerative conditions such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and retinal detachment have different etiologies and pathological characteristics, they also have many responses in common at the cellular level, including neural and glial remodeling. Structural changes in Müller cells, the large radial glia of the retina in retinal disease and injury have been well described, that of the retinal astrocytes remains less so. Using modern imaging technology to describe the structural remodeling of retinal astrocytes after retinal detachment is the focus of this paper. We present both a review of critical literature as well as novel work focusing on the responses of astrocytes following rhegmatogenous and serous retinal detachment. The mouse presents a convenient model system in which to study astrocyte reactivity since the Müller cell response is muted in comparison to other species thereby allowing better visualization of the astrocytes. We also show data from rat, cat, squirrel, and human retina demonstrating similarities and differences across species. Our data from immunolabeling and dye-filling experiments demonstrate previously undescribed morphological characteristics of normal astrocytes and changes induced by detachment. Astrocytes not only upregulate GFAP, but structurally remodel, becoming increasingly irregular in appearance, and often penetrating deep into neural retina. Understanding these responses, their consequences, and what drives them may prove to be an important component in improving visual outcome in a variety of therapeutic situations. Our data further supports the concept that astrocytes are important players in the retina’s overall response to injury and disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Astrocyte structural reactivity and plasticity in models of retinal detachment

Luna

Keeley

Reese

et al. 2016

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…Reactive astrogliosis may contribute to pericyte demise, causing a reduced pericyte overlay of cerebral blood vessels and worsened vascular reactivity. This, in turn, may modify the normal cerebral circulation and thus contribute to the disease progression (Hsiao et al ., 2015). …”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

View full text Add to dashboard Cite

Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

show abstract

“…Besides the most commonly functional abnormalities described in HD pathology, it has been recently reported that the cerebral vascular system is also significantly disrupted in the disease34.…”

mentioning

confidence: 99%

Impairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease

Pardo

Amico

Scalabrì

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Blood-brain barrier (BBB) breakdown, due to the concomitant disruption of the tight junctions (TJs), normally required for the maintenance of BBB function, and to the altered transport of molecules between blood and brain and vice-versa, has been suggested to significantly contribute to the development and progression of different brain disorders including Huntington’s disease (HD). Although the detrimental consequence the BBB breakdown may have in the clinical settings, the timing of its alteration remains elusive for many neurodegenerative diseases. In this study we demonstrate for the first time that BBB disruption in HD is not confined to established symptoms, but occurs early in the disease progression. Despite the obvious signs of impaired BBB permeability were only detectable in concomitance with the onset of the disease, signs of deranged TJs integrity occur precociously in the disease and precede the onset of overt symptoms. To our perspective this finding may add a new dimension to the horizons of pathological mechanisms underlying this devastating disease, however much remains to be elucidated for understanding how specific BBB drug targets can be approached in the future.

show abstract

Aberrant astrocytes impair vascular reactivity in Huntington disease

Cited by 79 publications

References 45 publications

Astrocyte structural reactivity and plasticity in models of retinal detachment

Astrocyte structural reactivity and plasticity in models of retinal detachment

Translational potential of astrocytes in brain disorders

Impairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease

Contact Info

Product

Resources

About