4.6 Article

Ependymal Ciliary Dysfunction and Reactive Astrocytosis in a Reorganized Subventricular Zone after Stroke

期刊

CEREBRAL CORTEX
卷 23, 期 3, 页码 647-659

出版社

OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhs049

关键词

cerebrospinal fluid; ependymal cells; neurogenesis; planar cell polarity; reactive astrocytes; stroke; subventricular zone

资金

  1. Rhodes Scholarship
  2. National Institutes of Health [RO1 NS-42253]
  3. Medical Research Council UK
  4. Foundation Leducq
  5. Medical Research Council [G0500495] Funding Source: researchfish

向作者/读者索取更多资源

Subventricular zone (SVZ) astrocytes and ependymal cells are both derived from radial glia and may have similar gliotic reactions after stroke. Diminishing SVZ neurogenesis worsens outcomes in mice, yet the effects of stroke on SVZ astrocytes and ependymal cells are poorly understood. We used mouse experimental stroke to determine if SVZ astrocytes and ependymal cells assume similar phenotypes and if stroke impacts their functions. Using lateral ventricular wall whole mount preparations, we show that stroke caused SVZ reactive astrocytosis, disrupting the neuroblast migratory scaffold. Also, SVZ vascular density and neural proliferation increased but apoptosis did not. In contrast to other reports, ependymal denudation and cell division was never observed. Remarkably, however, ependymal cells assumed features of reactive astrocytes post stroke, robustly expressing de novo glial fibrillary acidic protein, enlargening and extending long processes. Unexpectedly, stroke disrupted motile cilia planar cell polarity in ependymal cells. This suggested ciliary function was affected and indeed ventricular surface flow was slower and more turbulent post stroke. Together, these results demonstrate that in response to stroke there is significant SVZ reorganization with implications for both pathophysiology and therapeutic strategies.

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