CNS pericytes: Concepts, misconceptions, and a way out

Krueger, Martin W.; Bechmann, Ingo

doi:10.1002/glia.20898

Cited by 227 publications

(194 citation statements)

References 89 publications

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“…Thus, there may be functional differences of PCs depending on their location in the vascular tree. 20 Although endothelial cell death and vascular rarefaction occurred in the ischemic brain tissue, PC loss appears to precede and exceed vessel degeneration in our MCAO model. PC loss represents a previously unrecognized feature of brain ischemia and reperfusion injury, whose impact needs to be further characterized.…”

Section: Loss Of Capillary Pericytesmentioning

confidence: 67%

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Fernández-Klett

Potas

Hilpert

et al. 2012

J Cereb Blood Flow Metab

205

249

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Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRb) þ and CD105 þ stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRb þ stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.

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Section: Loss Of Capillary Pericytesmentioning

confidence: 67%

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Fernández-Klett

Potas

Hilpert

et al. 2012

J Cereb Blood Flow Metab

205

249

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“…1C). These features are hallmarks of brain pericytes (8). The characteristic morphology of a GFP-positive pericyte with circumferential processes arising from the cell body is shown in Fig.…”

Section: Pericytes In Acute Brain Slice Preparations Constrict In Resmentioning

confidence: 93%

Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain

Fernández-Klett

Offenhauser²,

Dirnagl³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

346

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Modern functional imaging techniques of the brain measure local hemodynamic responses evoked by neuronal activity. Capillary pericytes recently were suggested to mediate neurovascular coupling in brain slices, but their role in vivo remains unexplored. We used two-photon microscopy to study in real time pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized mice, as well as in brain slices. The thromboxane A 2 analog, 9,11-dideoxy-9α,11α-methanoepoxy Prostaglandin F2α (U46619), induced constrictions in the vicinity of pericytes in a fraction of capillaries, whereas others dilated. The changes in vessel diameter resulted in changes in capillary red blood cell (RBC) flow. In contrast, during brief epochs of seizure activity elicited by local administration of the GABA A receptor antagonist, bicuculline, capillary RBC flow increased without pericyte-induced capillary diameter changes. Precapillary arterioles were the smallest vessels to dilate, together with penetrating and pial arterioles. Our results provide in vivo evidence that pericytes can modulate capillary blood flow in the brain, which may be important under pathological conditions. However, our data suggest that precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity.cerebral blood flow | neurovascular coupling | cortical spreading depolarization | electrophysiology

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“…Both pericytes and ECs are considered to be involved in this capillary remodeling (Krueger and Bechmann, 2010;Rucker et al, 2000).…”

Section: Clinical Relevance Of Capillary Flow Controlmentioning

confidence: 99%

Control of Brain Capillary Blood Flow

Itoh

Suzuki

2012

J Cereb Blood Flow Metab

129

131

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While it has been widely confirmed that cerebral blood flow is closely coupled with brain metabolism, it remains a matter of controversy whether capillary flow is directly controlled to meet the energy demands of the parenchyma. Since the capillary is known to lack smooth muscle cells, it has generally been considered that capillary flow is not regulated in situ. However, we now have increasing data supporting the physiological control of capillary flow. The observation of heterogeneity in the microcirculation in vivo has suggested that intravascular factors may be involved in the flow control, including non-Newtonian rheology, red blood cell flow, leukocyte adhesion, release of vasoactive mediators, and expression of glycoproteins on the endothelial cells. Astrocytes, a key mediator of the neurovascular unit, and intrinsic innervation may also regulate capillary flow. In addition, recent findings on pericyte contractility have attracted the attention of many researchers. Finally, based on these findings, we present a new model of flow control, the proximal integration model, in which localized neural activity is detected at nearby capillaries and the vasodilation signal is transmitted proximally along the vessel. Signals are then integrated at the precapillary arterioles and other arterioles further upstream and regulate the capillary flow.

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CNS pericytes: Concepts, misconceptions, and a way out

Cited by 227 publications

References 89 publications

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain

Control of Brain Capillary Blood Flow

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