Turnover of Rat Brain Perivascular Cells

Bechmann, Ingo; Kwidzinski, Erik; Kovac, Adam D.; Simbürger, Eva; Horváth, Tamas L.; Gimsa, Ulrike; Dirnagl, Ulrich; Priller, Josef; Nitsch, Robert

doi:10.1006/exnr.2000.7618

Cited by 113 publications

(91 citation statements)

References 33 publications

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“…After intracranial injection, the hydrophilic fluorescent dextran dyes diffuse along the perivascular space and are absorbed by essentially all perivascular macrophages (>98%) via non-specific micropinocytosis. 25,30,49 To establish a baseline for subsequent perivascular macrophage turnover, all animals (n Z 12) received fluoresceinconjugated dextran (abbreviated Dextran:FITC; Molecular Probes) at 20 dpi (Table 1). Five animals received a second injection of Alexa Fluor 647econjugated dextran (abbreviated Dextran:AF647; Molecular Probes) 48 hours before necropsy to determine macrophage recruitment from 20 dpi necropsy.…”

Section: Intracisternal Injection Of Dextran Amines and Detection In mentioning

confidence: 99%

“…Previous studies on the rate of perivascular macrophage turnover in rodents (approximately 8% per week, as determined in mouse bone marrow chimeras, and approximately 2% per week, as determined by serial dextran labeling in rats) indicate that the total population of perivascular macrophages is replaced over several months, although individual macrophages may reside in the CNS for years. 30,31,49,68 The slow turnover rate of perivascular macrophages in the CNS, some of which may be infected, likely contributes to the maintenance of a viral reservoir in the CNS with HIV or SIV infection. Previous research indicates that the number of activated macrophages in the CNS better correlates with HIV dementia than viral replication in the CNS.…”

Section: Timing Of Siv Infection Of the Cns And Development Of Aids Amentioning

confidence: 99%

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SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163 þ ) and inflammatory (MAC387 þ ) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2 0 -deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387 þ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163 þ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU þ cells were MAC387 þ ; however, CD163 þ BrdU þ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% AE 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28 þ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163 þ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163 þ macrophage recruitment (P Z 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS.

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Section: Intracisternal Injection Of Dextran Amines and Detection In mentioning

confidence: 99%

Section: Timing Of Siv Infection Of the Cns And Development Of Aids Amentioning

confidence: 99%

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Nowlin

Burdo

Midkiff

et al. 2015

The American Journal of Pathology

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“…However, we believe that proliferation of perivascular macrophages is minor in the model studied here, because these cells were generally not distributed in clusters, as expected if they proliferated, but were rather scattered individually. The infiltration of monocytes into the perivascular space is not a consequence of irradiation, as suggested for microglia (Mildner et al, 2007), because it has been shown that monocytes, labeled ex vivo and injected into the circulation of normal mice, can give rise to perivascular macrophages (Bechmann et al, 2001a). The reason for this infiltration is unclear, but we speculate that it serves to replace phagocytic cells cleared by apoptosis, replace antigen-presenting cells that migrate to draining lymph nodes, and/or increase the number of sentinels in prevision of a future immune attack.…”

Section: Discussionmentioning

confidence: 99%

Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2

Audoy-Rémus¹,

Richard²,

Soulet³

et al. 2008

J. Neurosci.

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The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment is mostly unknown. Here, we provide evidence that CD68 ϩ GR1 Ϫ monocytes can give rise to perivascular macrophages in mice suffering from endotoxemia. After adhesion to the endothelium, these monocytes start to crawl, adopt a rod-shaped morphology when passing through capillaries, and can manifest the ability to proliferate and form a long cytoplasmic protuberance. They are attracted in greater numbers during endotoxemia by a combination of vasoregulatory molecules, including TNF (tumor necrosis factor), interleukin-1␤, and angiopoietin-2. After a period of several hours, some of them cross the endothelium to expand the population of perivascular macrophages. Depletion of adherent monocytes and perivascular macrophages can be achieved by injection of anti-angiopoietin-2 peptide-Fc fusion protein. This study extends our understanding of the behavior of monocytes at the blood-brain interface and provides a way to block their infiltration into the nervous tissue under inflammatory conditions.

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“…28,32-38 Parenchymal macrophage populations in all other regions of the CNS belong largely to the latter population and in the literature are most often referred to simply as microglia. 28,[32][33][34][35][36][37][38] Irradiation is not a neutral treatment and results in long-term alterations in the vasculature even when the heads are shielded from irradiation, likely a consequence of the cytokine storm associated with death of bone marrow and tissue macrophages throughout the body. 28,32-38 It has been suggested in studies of peripheral macrophages that irradiation chimeric methodologies cause premature death and turnover and thus result in overestimates of tissue macrophage turnover.…”

Section: A Rose By Any Other Name…?mentioning

confidence: 99%

A Rose by Any Other Name? The Potential Consequences of Microglial Heterogeneity During CNS Health and Disease

et al. 2007

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SummaryMicroglial activation and macrophage infiltration into the CNS are common features of CNS autoimmune disease and of chronic neurodegenerative diseases. Because these cells largely express an overlapping set of common macrophage markers, it has been difficult to separate their respective contributions to disease onset and progression. This problem is further confounded by the many types of macrophages that have been termed microglia. Several approaches, ranging from molecular profiling of isolated cells to the generation of irradiation chimeric rodent models, are now beginning to generate rudimentary definitions distinguishing the various types of microglia and macrophages found within the CNS and the potential roles that these cells may play in health and disease.

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Turnover of Rat Brain Perivascular Cells

Cited by 113 publications

References 33 publications

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2

A Rose by Any Other Name? The Potential Consequences of Microglial Heterogeneity During CNS Health and Disease

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