Effect of Vimentin on Reactive Gliosis:<i>In Vitro</i>and<i>In Vivo</i>Analysis

Lin, Jiangkai; Cai, Wenqin

doi:10.1089/neu.2004.21.1671

Cited by 21 publications

(8 citation statements)

References 55 publications

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“…jneurosci.org as supplemental material). This type of morphological change in astrocytes is similar to what occurs in reactive astrocytosis in vivo (Boukhelifa et al, 2003;Lin and Cai, 2004;Wilhelmsson et al, 2006). Hypertrophy of cellular processes and increased GFAP expression are two hallmarks of reactive astrocytes after all forms of neural injury in vivo (Wilhelmsson et al, 2004), suggesting the possibility that LCN2 may mediate reactive astrocytosis in vivo.…”

Section: Lcn2-induced Morphological Change Of Astrocytessupporting

confidence: 59%

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Lee¹,

Park²,

Lee³

et al. 2009

J. Neurosci.

236

238

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Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is a member of the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

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Section: Lcn2-induced Morphological Change Of Astrocytessupporting

confidence: 59%

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Lee¹,

Park²,

Lee³

et al. 2009

J. Neurosci.

236

238

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“…Additionally, we are unsure as to the precise link between vimentin expression in individual reactive glia and the area of gliosis in songbirds. In mice, recent in vitro and in vivo studies report decreased astrocytic proliferation and glial scar formation, respectively, following compromise of vimentin expression by injection of RNA antisense to vimentin (Lin and Cai, 2004). These data suggest that vimentin is necessary for normal intermediate filament assembly and glial scar formation following central nervous system insult Pekny and Nilsson, 2005;Pekny et al, 1999).…”

Section: Discussionmentioning

confidence: 75%

Inhibition of injury‐induced glial aromatase reveals a wave of secondary degeneration in the songbird brain

Wynne

Walters

Bailey

et al. 2007

Glia

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Mechanical or anoxic/ischemic brain insult results in reactive gliosis and a pronounced wave of apoptotic secondary degeneration (WSD). Reactive glia express aromatase (estrogen synthase) and glial estrogen synthesis decreases apoptosis and the volume of degeneration. Whether aromatization by glia affects gliosis itself or the initiation/maintenance of the WSD remains unknown. Adult male zebra finches (Taeniopygia guttata) were injured with a needle that contained the aromatase inhibitor fadrozole or vehicle into contralateral hemispheres. Birds were killed at 0, 2, 6, 24, 72h, 2 or 6 weeks postinjury. Gliosis and degeneration were measured with vimentin- and Fluoro-Jade B-expression, respectively. Reactive gliosis was detectable at 6 h, reached asymptote at 72 h, and continued until 6 weeks postinsult. Gliosis extended further around fadrozole-injury than vehicle, an effect driven by a larger area of gliosis around fadrozole- relative to vehicle-injury at 72 h postinsult. Glial aromatase was inhibited for about 2 weeks postinjury since aromatase relative optical density was higher around fadrozole-injury relative to vehicle-injury until this time-point. Degeneration around vehicle-injury reached asymptote at 2 h postinsult, but that around fadrozole-injury peaked 24-72 h postinjury and decreased thereafter. Thus, the injury-induced WSD as described in mammals is detectable in zebra finches only following glial aromatase inhibition. In the zebra finch, injury-induced estrogen provision may decrease reactive gliosis and severely dampen the WSD, suggesting that songbirds are powerful models for understanding the role of glial aromatization in secondary brain damage.

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“…Using primary astrocyte cultures of vimentin knock-out mice, it was pointed out that vimentin appeared to be necessary to stabilize GFAP filaments and the intermediate filament network formation [92]. Accordingly, in vitro transfection experiments showed that the growth of astrocytes is inhibited when vimentin expression is decreased [99]. …”

Section: Canine Distemper Leukoencephalitis — Novel Aspects Of Itsmentioning

confidence: 99%

New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

Lempp

Spitzbarth

Puff

et al. 2014

Viruses

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Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes, expression of vimentin is generally restricted to immature or reactive astrocytes. Thus, vimentin-positive astrocytes might constitute an important cell population for CDV persistence and spread, as well as lesion progression. In vitro models, such as dissociated glial cell cultures, as well as organotypic brain slice cultures have contributed to a better insight into mechanisms of infection and certain morphological and molecular aspects of CDV-DL. Summarized, recent in vivo and in vitro studies revealed remarkable new aspects of nervous distemper. These new perceptions substantially improved our understanding of the pathogenesis of CDV-DL and might represent new starting points to develop novel treatment strategies.

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Effect of Vimentin on Reactive Gliosis:In VitroandIn VivoAnalysis

Cited by 21 publications

References 55 publications

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis

Inhibition of injury‐induced glial aromatase reveals a wave of secondary degeneration in the songbird brain

New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

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