PubMed Health⌕ Search

Biomedical subjects

Paula Dore-Duffy

Publications and source records attributed to Paula Dore-Duffy.

6 recordsLinked to original sources
PubMed2006

CNS microvascular pericytes exhibit multipotential stem cell activity.

It has been suggested that a vascular-like cell has multipotent regenerative and mesenchymal lineage relationships. The identity of this stem/progenitor cell has remained elusive. We report here that adult central nervous system (CNS) capillaries contain a distinct population of microvascular cells, the pericyte that are nestin/NG2 positive and in response to basic fibroblast growth factor (bFGF) differentiate into cells of neural lineage. In their microvascular location, pericytes express nestin and NG2 proteoglycan. In serum containing media primary (0 to 7 day old) CNS pericytes are nestin positive, NG2 positive, alpha smooth muscle actin (alphaSMA) positive, and do not bind the endothelial cell specific griffonia symplicifolia agglutinin (GSA). In serum containing media, pericytes do not undergo neurogenesis but are induced to express alphaSMA. In bFGF containing media without serum, CNS pericytes form small clusters and multicellular spheres. Differentiated spheres expressed neuronal and glial cell markers. After disruption and serial dilution, differentiated spheres were capable of self-renewal. When differentiated spheres were disrupted and cultured in the presence of serum, multiple adherent cell populations were identified by dual and triple immunocytochemistry. Cells expressing markers characteristic of pericytes, neurons, and glial cells were generated. Many of the cells exhibited dual expression of differentiation markers. With prolonged culture fully differentiated cells of neural lineage were present. Results indicate that adult CNS microvascular pericytes have neural stem cell capability.

Animals↗
PubMed2005

New frontiers in translational research in neuro-oncology and the blood-brain barrier: report of the tenth annual Blood-Brain Barrier Disruption Consortium Meeting.

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB, delivery of agents to the CNS, neuroimaging, angiogenesis, immunotherapy, and gene therapy, as well as glioma, primary CNS lymphoma, and metastases to the CNS were discussed. Transport across the BBB relates to the neurovascular unit, which consists not only of endothelial cells but also of pericyte, glia, and neuronal elements.

Antineoplastic Agents↗
PubMed2005

The CNS pericyte response to low oxygen: early synthesis of cyclopentenone prostaglandins of the J-series.

Exposure to low oxygen induces adaptive changes at the microvascular level that are beneficial to cell survival. These adaptive changes involve complex signaling mechanisms between the vascular endothelial cell and the pericyte, and are important to the maintenance of vascular homeostasis and hemostasis. We have investigated the early response of the central nervous system (CNS) microvascular pericyte to low oxygen. In vitro exposure of primary rat CNS pericytes to low oxygen induced the rapid synthesis and release of the cyclopentenone prostaglandin (PG) PGD2 and PGJ2 within 15-30 min following hypoxic stress signal. Hypoxia-induced release of PGD2/PGJ2 was COX-1 dependent and did not involve COX-2. The exogenous addition of 15-deoxyDelta(12,14) PGJ2 to pericytes under normoxic conditions increased glut-1 protein in the absence of hypoxia. PGD2 and PGJ2 may be early signaling molecules in the pericyte stress response.

Animals↗
PubMed2002

Cytokine regulation of E-selectin in rat CNS microvascular endothelial cells: differential response of CNS and non-CNS vessels.

We have compared the induced expression of E-selectin in primary cultures of rat brain microvascular endothelial cells (EC), pericytes and in non-CNS microvascular endothelium stimulated with the cytokines, IL-1beta (20 ng/ml), and tumor necrosis factor (TNF)-alpha (75 ng/ml). Expression was studied at both the protein and mRNA levels. Fluorescence in-situ hybridization (FISH) was used to examine de novo synthesis of E-selectin mRNA. Laser cytometric analysis was used as a novel approach to the quantitaion of FISH. In-situ hybridization was performed using two PCR-generated probes. The first probe (517 bp) spanned the lectin and epidermal growth factor (EGF)-like domain. The second probe (562 bp) spanned the CR3, 4, and 6 domains. E-selectin-specific mRNA was localized to the perinuclear regions of the EC. Both cytokines, IL-1beta and TNF-alpha significantly increased E-selectin gene expression in CNS EC but not pericytes. IL-1beta induced higher E-selectin mRNA levels than TNF-alpha. The maximum number of mRNA-positive cells was observed after stimulation for 4--6 h. Surface protein expression was sustained for up to 48 h following addition of cytokine. This was in contrast to the transient expression in non-CNS EC indicating that pure primary CNS EC display slightly different kinetics of E-selectin expression than non-CNS EC.

Animals↗
PubMedDate not supplied

Glucocorticoid-induced apoptosis in CNS microvascular pericytes.

Pericyte loss or migration from its vascular location may be an important step in microvascular remodeling. Decreased pericyte to endothelial ratios are characteristics of newly formed vessels as well as microvessels undergoing regression, and may be due to selective degeneration via necrotic cell death or via programmed cell death. In this study, we have examined glucocorticoid-induced apoptosis in primary rat CNS pericytes. Characterization of apoptosis was determined using five independent criteria: (1) the translocation of receptors for annexin V from the inner to the outer surface of the plasma membrane, (2) the translocation of cytochrome C from the mitochondria to the cytosol, (3) the induction of DNA fragmentation, (4) the induction of classic changes in cell morphology, and (5) the appearance of TUNEL-positive cells. Incubation of CNS pericytes with dexamethasone induced the appearance of apoptotic cells in a time- and dose-dependent manner. Pericytes express immunologically detectable glucocorticoid receptors, and addition of the glucocorticoid receptor antagonist mifepristone inhibited dexamethasone-induced pericyte apoptosis. That pericytes undergo apoptosis in response to dexamethasone suggests that the regulatory function of this steroid may be important in vascular development and that pericyte apoptotic cell death may accompany vascular regression. Deregulation of pericyte involvement in vascular homeostasis and hemostasis may result in clinical disease.

Animals↗