During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by... more During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68(+) microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin(+) (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7(high) DCX(low) hNPCs and P2X7(high) DCX(high) neuroblasts, derived from primary cultures of human fetal tel...
The cat eye was used to determine the long-term morphological changes in the corneal endothelium ... more The cat eye was used to determine the long-term morphological changes in the corneal endothelium that occur after central endothelial wounding. Central corneal thickness was measured using ultrasonic pachometry. Specular microscopy and computer-assisted morphometry was used to quantify central and peripheral endothelial cell density (ECD), coefficient of variation (COV) and the mean and standard deviation of the shape factor (S)
American journal of physiology. Endocrinology and metabolism, Jan 24, 2015
Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D).... more Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D). However, little is known about the mediators of these effects. We asked whether expression of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3), known to be neuroprotective, were altered in the brain of T1D mice compared to age-matched controls. Levels of matrix metalloprotease-2 (MMP2) and nucleoside triphosphate diphosphohydrolase-1 (CD39) were utilized to assess changes in astrocytes, microglia and blood vessels. In the diabetic hypothalamus (HYPO), we observed that neuronal soma diameter was reduced by 20% (p<0.05) and neuronal expression of IGFBP-3 and IGF-1 was reduced by 32% (p<0.05) and 15% (p<0.05), respectively, compared to controls. Inflammatory markers (MMP2 and Iba-1) were increased in astrocytes (46%, p<0.01) and microglia (29%, p<0.05). CD39 expression was reduced by 27% (p<0.05) in microglia and blood vessels. Inflammatory changes...
Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neo... more Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neovascularization. However, a growing body of evidence indicates that VEGF also acts on non-vascular cells, both developmentally as well as in the adult. In light of the widespread use of systemic and intraocular anti-VEGF therapies for the treatment of angiogenesis associated with tumor growth and wet macular degeneration, systematic investigation of the role of VEGF in the adult retina is critical. Using immunohistochemistry and Lac-Z reporter mouse lines, we report that VEGF is produced by various cells in the adult mouse retina and that VEGFR2, the primary signaling receptor, is also widely expressed, with strong expression by Müller cells and photoreceptors. Systemic neutralization of VEGF was accomplished in mice by adenoviral expression of sFlt1. After 14 days of VEGF neutralization, there was no effect on the inner and outer retina vasculature, but a significant increase in apoptos...
Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigat... more Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (Plasmodium berghei ANKA (PbA) infection). C57BL/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. This pathology was not seen in PbA-infected,
Homeostasis implies constant operational defence mechanisms, against both external and internal t... more Homeostasis implies constant operational defence mechanisms, against both external and internal threats. Infectious agents are prominent among such threats. During infection, the host elicits the release of a vast array of molecules and numerous cell-cell interactions are triggered. These pleiomorphic mediators and cellular effects are of prime importance in the defence of the host, both in the systemic circulation and at sites of tissue injury, for example, the blood-brain barrier (BBB). Here, we focus on the interactions between the endothelium, astrocytes, and the molecules they release. Our review addresses these interactions during infectious neurological diseases of various origins, especially cerebral malaria (CM). Two novel elements of the interplay between endothelium and astrocytes, microparticles and the kynurenine pathway, will also be discussed.
To determine the roles of vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and An... more To determine the roles of vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and Ang-2 in nasal polyps (NPs) by assaying expression patterns and evaluating the effects of dexamethasone (DEX) on these factors in organ cultured NPs. Prospective. Expression patterns of VEGF, Ang-1, and Ang-2 in NPs were compared with those in inferior turbinate mucosa samples. Tissue samples were analyzed using the enzyme-linked immunosorbent assay (ELISA) and immunofluorescent staining methods. To determine the effects of DEX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 microM or 100 microM) for 24 hours, and tissue samples analyzed with ELISA. VEGF and Ang-1 levels were significantly higher, whereas the Ang-2 level was significantly lower in NPs, compared to inferior turbinate mucosa (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). In NPs, VEGF and Ang-1 were detected in glandular epithelial, vascular endothelial, as well as stromal inflammatory cells, whereas Ang-2 was detected only in stromal inflammatory cells. VEGF and Ang-1 levels were significantly lower, while Ang-2 levels were significantly higher in 100 microM DEX-treated group than nontreated group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Imbalance among VEGF, Ang 1, and Ang 2 may be important in the angiogenesis of NPs. Moreover, DEX can control the expression of these factors in NPs. We suggest that VEGF and Ang-1 act as positive regulatory factors, and Ang-2 functions as a negative regulatory factor of angiogenesis in NPs.
During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by... more During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68(+) microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin(+) (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7(high) DCX(low) hNPCs and P2X7(high) DCX(high) neuroblasts, derived from primary cultures of human fetal tel...
The cat eye was used to determine the long-term morphological changes in the corneal endothelium ... more The cat eye was used to determine the long-term morphological changes in the corneal endothelium that occur after central endothelial wounding. Central corneal thickness was measured using ultrasonic pachometry. Specular microscopy and computer-assisted morphometry was used to quantify central and peripheral endothelial cell density (ECD), coefficient of variation (COV) and the mean and standard deviation of the shape factor (S)
American journal of physiology. Endocrinology and metabolism, Jan 24, 2015
Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D).... more Neuroinflammation and neurodegeneration have been observed in the brain in type 1 diabetes (T1D). However, little is known about the mediators of these effects. We asked whether expression of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3), known to be neuroprotective, were altered in the brain of T1D mice compared to age-matched controls. Levels of matrix metalloprotease-2 (MMP2) and nucleoside triphosphate diphosphohydrolase-1 (CD39) were utilized to assess changes in astrocytes, microglia and blood vessels. In the diabetic hypothalamus (HYPO), we observed that neuronal soma diameter was reduced by 20% (p<0.05) and neuronal expression of IGFBP-3 and IGF-1 was reduced by 32% (p<0.05) and 15% (p<0.05), respectively, compared to controls. Inflammatory markers (MMP2 and Iba-1) were increased in astrocytes (46%, p<0.01) and microglia (29%, p<0.05). CD39 expression was reduced by 27% (p<0.05) in microglia and blood vessels. Inflammatory changes...
Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neo... more Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neovascularization. However, a growing body of evidence indicates that VEGF also acts on non-vascular cells, both developmentally as well as in the adult. In light of the widespread use of systemic and intraocular anti-VEGF therapies for the treatment of angiogenesis associated with tumor growth and wet macular degeneration, systematic investigation of the role of VEGF in the adult retina is critical. Using immunohistochemistry and Lac-Z reporter mouse lines, we report that VEGF is produced by various cells in the adult mouse retina and that VEGFR2, the primary signaling receptor, is also widely expressed, with strong expression by Müller cells and photoreceptors. Systemic neutralization of VEGF was accomplished in mice by adenoviral expression of sFlt1. After 14 days of VEGF neutralization, there was no effect on the inner and outer retina vasculature, but a significant increase in apoptos...
Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigat... more Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (Plasmodium berghei ANKA (PbA) infection). C57BL/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. This pathology was not seen in PbA-infected,
Homeostasis implies constant operational defence mechanisms, against both external and internal t... more Homeostasis implies constant operational defence mechanisms, against both external and internal threats. Infectious agents are prominent among such threats. During infection, the host elicits the release of a vast array of molecules and numerous cell-cell interactions are triggered. These pleiomorphic mediators and cellular effects are of prime importance in the defence of the host, both in the systemic circulation and at sites of tissue injury, for example, the blood-brain barrier (BBB). Here, we focus on the interactions between the endothelium, astrocytes, and the molecules they release. Our review addresses these interactions during infectious neurological diseases of various origins, especially cerebral malaria (CM). Two novel elements of the interplay between endothelium and astrocytes, microparticles and the kynurenine pathway, will also be discussed.
To determine the roles of vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and An... more To determine the roles of vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and Ang-2 in nasal polyps (NPs) by assaying expression patterns and evaluating the effects of dexamethasone (DEX) on these factors in organ cultured NPs. Prospective. Expression patterns of VEGF, Ang-1, and Ang-2 in NPs were compared with those in inferior turbinate mucosa samples. Tissue samples were analyzed using the enzyme-linked immunosorbent assay (ELISA) and immunofluorescent staining methods. To determine the effects of DEX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 microM or 100 microM) for 24 hours, and tissue samples analyzed with ELISA. VEGF and Ang-1 levels were significantly higher, whereas the Ang-2 level was significantly lower in NPs, compared to inferior turbinate mucosa (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). In NPs, VEGF and Ang-1 were detected in glandular epithelial, vascular endothelial, as well as stromal inflammatory cells, whereas Ang-2 was detected only in stromal inflammatory cells. VEGF and Ang-1 levels were significantly lower, while Ang-2 levels were significantly higher in 100 microM DEX-treated group than nontreated group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Imbalance among VEGF, Ang 1, and Ang 2 may be important in the angiogenesis of NPs. Moreover, DEX can control the expression of these factors in NPs. We suggest that VEGF and Ang-1 act as positive regulatory factors, and Ang-2 functions as a negative regulatory factor of angiogenesis in NPs.
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