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Review
. 2017;15(6):892-905.
doi: 10.2174/1570159X15666170112170226.

Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke

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Free PMC article
Review

Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke

Shuai Yang et al. Curr Neuropharmacol. .
Free PMC article

Abstract

Background: Every year, strokes take millions of lives and leave millions of individuals living with permanent disabilities. Recently more researchers embrace the concept of the neurovascular unit (NVU), which encompasses neurons, endothelial cells (ECs), pericytes, astrocyte, microglia, and the extracellular matrix. It has been well-documented that NVU emerged as a new paradigm for the exploration of mechanisms and therapies in ischemic stroke. To better understand the complex NVU and broaden therapeutic targets, we must probe the roles of multiple cell types in ischemic stroke. The aims of this paper are to introduce the biological characteristics of brain pericytes and the available evidence on the diverse functions and mechanisms involving the pericytes in the context of ischemic stroke.

Methods: Research and online content related to the biological characteristics and pathophysiological roles of pericytes is review. The new research direction on the Pericytes in ischemic stroke, and the potential therapeutic targets are provided.

Results: During the different stages of ischemic stroke, pericytes play different roles: 1) On the hyperacute phase of stroke, pericytes constriction and death may be a cause of the no-reflow phenomenon in brain capillaries; 2) During the acute phase, pericytes detach from microvessels and participate in inflammatory-immunological response, resulting in the BBB damage and brain edema. Pericytes also provide benefit for neuroprotection by protecting endothelium, stabilizing BBB and releasing neurotrophins; 3) Similarly, during the later recovery phase of stroke, pericytes also contribute to angiogenesis, neurogenesis, and thereby promote neurological recovery.

Conclusion: This emphasis on the NVU concept has shifted the focus of ischemic stroke research from neuro-centric views to the complex interactions within NVU. With this new perspective, pericytes that are centrally positioned in the NVU have been widely studied in ischemic stroke. More work is needed to elucidate the beneficial and detrimental roles of brain pericytes in ischemic stroke that may serve as a basis for potential therapeutic targets.

Keywords: BBB; NVU; Pericytes; ischemic stroke; mechanisms; therapeutic targets.

Figures

Fig. (1)
Fig. (1)
The multifunction role of brain pericytes at the neurovascular unit. Schematic representation showing a simplified NVU that encompasses neurons, endothelial cells (ECs), pericytes, astrocyte, microglia, and the basement membrane. Pericytes can regulate capillary diameter and CBF, BBB permeability, angiogenesis, phagocytosis, neuroinflammation and multipotent stem cell activity.
Fig. (2)
Fig. (2)
Brain pericytes anatomy. (a) Ultrastructural of brain pericytes. Brain pericytes nucleus is relatively large, kidney-shaped and protrudes into tubal antrum. The small amounts of perinuclear cytoplasm usually contain mitochondria, endoplasmic reticulum and lysosomes. Contractile microfilaments (containing actin, myosin and tropomyosin) and intermediate filaments are also observed in these cells. Numerous caveolae principally locate in abluminal pericytes surface and single caveolae usually appear in the processes of pericytes. In the areas lacking BM, pericytes and ECs form direct cell-to-cell contacts with each other by interdigitation, referred to as “peg-and-socket” contacts. These contacts include the connexin-43 hemichannels (CX-43) mediated gap junctions and N-cadherin based adherence junctions. The other type of contacts is “adhesion plaques”. (b) Topology and morphology of brain pericytes. Schematic showing the continuum of mural cell types along the cerebral microvessels. Brain arterioles wrapped by a continuous of vascular smooth muscle cells (vSMCs) further ramify and transit into smaller precapillary arterioles. The mural cells located in the point of transition show a mixed phenotype of vSMCs and pericytes, termed as “smooth muscle-pericytes hybrids”. Another type of pericytes at the precapillary arterioles, referred to as “mesh pericytes”, exhibit more interlocking mesh progresses. Pericytes in capillary beds have protruding cell bodies with thin strand or helical primary processes that run parallel to the long axis of mid-capillary tube. Mesh pericytes with many slender, branching processes become more prevalent on postcapillary venules. The boexs represent “arterioles-capillary junction”. (Reproduced from Hartmann et al. [32] with permission).

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