Stroke Induces Gene Profile Changes Associated with Neurogenesis and Angiogenesis in Adult Subventricular Zone Progenitor Cells

Abstract

Neural progenitor cells in the subventricular zone (SVZ) of the lateral ventricular wall give rise to new neurons throughout rodent life. Ischemic stroke induces angiogenesis and neurogenesis. Using laser capture microdissection (LCM) in combination with microarrays containing approximately 400 known genes associated with stem cells and angiogenesis, we investigated gene profiles of SVZ cells in the adult mouse subjected to middle cerebral artery occlusion. Our data revealed that nonstroke SVZ cells expressed sets of genes that are important for neural progenitor cell proliferation, differentiation, and migration. In addition, stroke SVZ cells expressed many genes involved in neurogenesis during embryonic development but were not detected in nonstroke SVZ cells. Stroke upregulated genes were verified by real-time reverse transcriptase-polymerase chain reaction and immunostaining. These data indicate that adult SVZ cells recapture embryonic molecular signals after stroke and provide insight into the molecular mechanisms, which regulate the biological function of neural progenitor cells in the SVZ of adult rodent brain under physiological and stroke conditions.

Function of neural stem cells in ischemic brain repair processes

“…Adult V/SVZ neural progenitor cells express miRNAs, and stroke induces robust alteration of miRNA profiles in these cells. [93][94][95] Stroke-altered miRNAs affect several signaling pathways including Notch, Shh, and Wnt. 93 For example, stroke increases miR-124a, the most abundant neuronal miRNA, expression in V/SVZ neural progenitor cells, and upregulated miR-124a inactivates Notch signaling by targeting a Notch ligand Jagged-1, which promotes neuronal differentiation.…”

Epigenetic Regulation of BMP7 in the Regenerative Response to Ischemia

“…Ischemia and subsequent reperfusion induce a variety of metabolic changes in the affected organs, including a decrease in the ATP levels, production of reactive oxygen species, and alterations in the intracellular ion and pH homeostasis. 9 -11 In organs damaged by ischemia, including the heart, 12,13 brain, 14,15 and kidney, 11,16 proteins that are involved in organogenesis during embryonic devel-opment have been shown to be re-induced. One of the unique features of the kidney, as compared with those of the heart and brain, is that it can regenerate almost completely after transient ischemia, making it an ideal organ system to study the mechanisms underlying regeneration after ischemia.…”

Hypoxia-controlled matrix metalloproteinase-9 hyperexpression promotes behavioral recovery after ischemia

“…Furthermore, as part of the neuroinfl ammatory response, MMP-9 may also lead to vasogenic or cytotoxic edema, hemorrhagic transformation, and neuronal apoptosis [10] . However, recently, MMP-9 has been implicated in tissue repair such as extracellular matrix remodeling, axonal regeneration, remyelination, and the facilitation of neurogenesis and angiogenesis [11][12][13][14] .…”