%0 Journal Article
%~ PubMed
%A Kur, Joanna
%A Newman, Eric A
%A Chan-Ling, Tailoi
%T Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease.
%B Progress in Retinal and Eye Research
%D 2012
%C United Kingdom
%I Pergamon
%V 31
%N 5
%P 377-406
%@ 1873-1635
%X We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer''s disease. We close by discussing issues that remain to be explored.
%Z FOR Codes: 111301


%0 Journal Article
%~ PubMed
%A Jarajapu, Yagna P R
%A Cai, Jun
%A Yan, Yuanqing
%A Li Calzi, Sergio
%A Kielczewski, Jennifer L
%A Hu, Ping
%A Shaw, Lynn C
%A Firth, Sue M
%A Chan-Ling, Tailoi
%A Boulton, Michael E
%A Baxter, Robert C
%A Grant, Maria B
%T Protection of blood retinal barrier and systemic vasculature by insulin-like growth factor binding protein-3.
%B PLoS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 7
%P e39398
%@ 1932-6203
%X 
%Z FOR Codes: 606


%0 Journal Article
%~ PubMed
%A Combes, Val??ry
%A Guillemin, Gilles J
%A Chan-Ling, Tailoi
%A Hunt, Nicholas H
%A Grau, Georges E R
%T The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes.
%B Trends in Parasitology
%D 2012
%C United Kingdom
%I Elsevier Ltd
%V 28
%N 8
%P 311-319
%@ 1471-5007
%X 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.
%Z FOR Codes: 1107


%0 Journal Article
%~ PubMed
%A Hunt, Glenn E
%A Van Nieuwenhuijzen, Petra S
%A Chan-Ling, Tailoi
%A McGregor, Iain S
%T 'When an old rat smells a cat': A decline in defense-related, but not accessory olfactory, Fos expression in aged rats.
%B Neurobiology of aging
%D 2011
%C United States
%I Elsevier Inc.
%V 32
%N 4
%P 737-49
%@ 1558-1497
%X Comparisons were made between young (3-6 months) and aged (20-30 months) Wistar rats on locomotor activity, emergence, social interaction and cat odor avoidance. Aged rats were less active and spent less time in the open field during the emergence test than younger rats. Older rats also showed fewer contacts with a novel conspecific in the social interaction test, although total duration of interaction did not differ. There were very few behavioral differences between male and female rats. Older rats were less reactive than younger rats in a test of cat odor avoidance. However, they expressed similar amounts of cat odor-induced Fos in the posterior accessory olfactory bulb, a critical region for processing the predator odor stimulus. Older rats had reduced Fos expression in several defense-related brain regions that are normally activated by predator odors such as the medial amygdala and dorsal premammillary nucleus. These results indicate that aged rats are less reactive than younger rats to predator odors due to decreased responsiveness in defense-related but not necessarily olfactory circuits.
%Z FOR Codes: 110903 110906


%0 Journal Article
%~ PubMed
%A Braidy, Nady
%A Guillemin, Gilles J
%A Mansour, Hussein
%A Chan-Ling, Tailoi
%A Poljak, Anne
%A Grant, Ross
%T Age related changes in NAD+ metabolism oxidative stress and sirt1 activity in wistar rats.
%B PloS one
%D 2011
%C United States
%I Public Library of Science
%V 6
%N 4
%P e19194
%@ 1932-6203
%X The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose) polymerase (PARP), an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD???NADH ratio in all organs by middle age (i.e.12 months) compared to young (i.e. 3 month old) rats. These changes in [NAD(H)] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine) formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX) was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Braidy, Nady
%A Guillemin, Gilles J
%A Mansour, Hussein
%A Chan-Ling, Tailoi
%A Grant, Ross
%T Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats.
%B The FEBS Journal
%D 2011
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 278
%N 22
%P 4425-4434
%@ 1742-4658
%X The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging. We quantified tryptophan and its metabolites kynurenine (KYN), kynurenine acid (KYNA), picolinic acid (PIC) and quinolinic acid (QUIN), and activity of the kynurenine pathway enzymes indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO) and quinolinic acid phosphoribosyltransferase (QPRTase), in the brain, liver and kidney of young, middle-aged and old female Wistar rats. Tryptophan levels and TDO activity decreased in all tissues with age. In contrast, brain IDO activity increased with age, while liver and kidney IDO activity decreased with age. The levels of KYN, KYNA, QUIN and PIC in brain all increased with age, while the levels of KYN in the liver and kidney showed a tendency to decrease. The levels of KYNA in the liver did not change, but the levels of KYNA in the kidney increased. The levels of PIC and QUIN increased significantly in the liver but showed a tendency to decrease in the kidney. QPRTase activity in both brain and liver decreased with age but was elevated in the kidney in middle-aged (12-month-old) rats. These age-associated changes in tryptophan metabolism have the potential to impact upon major biological processes, including lymphocyte function, pyridine (NAD(P)(H)) synthesis and N-methyl-d-aspartate (NMDA)-mediated synaptic transmission, and may therefore contribute to several degenerative changes of the elderly.
%Z FOR Codes: 1101


%0 Journal Article
%~ PubMed
%A Chan-Ling, Tailoi
%A Dahlstrom, Jane E
%A Koina, Mark E
%A McColm, Janet R
%A Sterling, Ruth-Ann
%A Bean, Elaine G
%A Adamson, Sam
%A Hughes, Suzanne
%A Baxter, Louise C
%T Evidence of hematopoietic differentiation, vasculogenesis and angiogenesis in the formation of human choroidal blood vessels.
%B Experimental Eye Research
%D 2011
%C United Kingdom, United States
%I Academic Press
%V 92
%N 5
%P 361-376
%@ 0014-4835
%X Human fetal eyes 8-40 weeks gestation (WG) were examined using markers to hematopoietic stem cells (HSC), vascular precursor cells (VPC), monocytes/macrophages and endothelial cells (EC). Electron microscopy and bromo-deoxyuridene labeling were undertaken to confirm the existence of solid vascular cords and to demonstrate vasculogenesis and angiogenesis in developing choroidal tissue. Our results demonstrated that the earliest incipient choroid consisted of vimentin(+) mesenchymal precursor cells which downregulated vimentin expression with maturation. Our observations lead us to conclude that these vimentin(-)/CD34(+)/CD44(+)/CD133(+) HSCs then differentiated into three distinct lineages: single isolated CD34(-)/CD39(+) VPCs that formed solid vascular cords which lumenized and became lined with CD34(+) vascular ECs; CD34(--+)/CD14(+)/CD68(+) monocytes that differentiated into tissue macrophages; and CD133(+)/CD34(--+)/??-smooth muscle actin(+) mural precursor cells that matured into smooth muscle cells and pericytes. Blood vessel formation occurred throughout the whole choroid simultaneously, indicative of in situ differentiation. Vasculogenesis, as evidenced by lumenization of solid vascular cords, was responsible for the formation of the entire choroidal area with angiogenesis, in all three layers of the choroid, only adding to vascular density. These results suggest that formation of the human choroid involves three processes: HSC differentiation, vasculogenesis and angiogenesis. Since vasculogenesis takes place independently of VEGF(165), further insights regarding the molecular mechanisms of vasculogenesis are required to better inform future treatments of choroidal neovascularization.
%Z FOR Codes: 1113


%0 Journal Article
%~ PubMed
%A Kielczewski, Jennifer L
%A Li Calzi, Sergio
%A Shaw, Lynn C
%A Cai, Jun
%A Qi, Xiaoping
%A Ruan, Qing
%A Wu, Lin
%A Liu, Li
%A Hu, Ping
%A Chan-Ling, Tailoi
%A Mames, Robert N
%A Firth, Sue
%A Baxter, Robert C
%A Turowski, Patric
%A Busik, Julia V
%A Boulton, Michael E
%A Grant, Maria B
%T Free insulin-like growth factor binding protein-3 (IGFBP-3) reduces retinal vascular permeability in association with a reduction of acid sphingomyelinase (ASMase).
%B Investigative Ophthalmology & Visual Science
%D 2011
%C United States
%I Association for Research in Vision and Ophthalmology
%V 52
%N 11
%P 8278-8286
%@ 0146-0404
%X To examine the effect of free insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), independent of the effect of insulin-like growth factors, in modulating retinal vascular permeability.
%Z FOR Codes: 111301


%0 Journal Article
%~ PubMed
%A Kielczewski, Jennifer L
%A Hu, Ping
%A Shaw, Lynn C
%A Li Calzi, Sergio
%A Mames, Robert N
%A Gardiner, Tom A
%A McFarland, Evan
%A Chan-Ling, Tailoi
%A Grant, Maria B
%T Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury.
%B The American Journal of Pathology
%D 2011
%C United States
%I American Society for Investigative Pathology
%V 178
%N 4
%P 1517-1528
%@ 0002-9440
%X This study was conducted to determine the perivascular cell responses to increased endothelial cell expression of insulin-like growth factor binding protein-3 (IGFBP-3) in mouse retina. The contribution of bone marrow cells in the IGFBP-3-mediated response was examined using green fluorescent protein-positive (GFP(+)) adult chimeric mice subjected to laser-induced retinal vessel occlusion injury. Intravitreal injection of an endothelial-specific IGFBP-3-expressing plasmid resulted in increased differentiation of GFP(+) hematopoietic stem cells (HSCs) into pericytes and astrocytes as determined by immunohistochemical analysis. Administration of IGFBP-3 plasmid to mouse pups that underwent the oxygen-induced retinopathy model resulted in increased pericyte ensheathment and reduced pericyte apoptosis in the developing retina. Increased IGFBP-3 expression reduced the number of activated microglial cells and decreased apoptosis of neuronal cells in the oxygen-induced retinopathy model. In summary, IGFBP-3 increased differentiation of GFP(+) HSCs into pericytes and astrocytes while increasing vascular ensheathment of pericytes and decreasing apoptosis of pericytes and retinal neurons. All of these cytoprotective effects exhibited by IGFBP-3 overexpression can result in a more stable retinal vascular bed. Thus, endothelial expression of IGFBP-3 may represent a physiologic response to injury and may represent a therapeutic strategy for the treatment of ischemic vascular eye diseases, such as diabetic retinopathy and retinopathy of prematurity.
%Z FOR Codes: 111301


%0 Journal Article
%~ PubMed
%A Ampawong, Sumate
%A Combes, Valéry
%A Hunt, Nicholas H
%A Radford, Jane
%A Chan-Ling, Tailoi
%A Pongponratn, Emsri
%A Grau, Georges E R
%T Quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria.
%B International Journal of Clinical and Experimental Pathology
%D 2011
%C United States
%I E-Century Publishing Corporation
%V 4
%N 6
%P 566-574
%@ 1936-2625
%X The pathogenic mechanisms underlying the occurrence of cerebral malaria (CM) are still incompletely understood but, clearly, cerebral complications may result from concomitant microvessel obstruction and inflammation. The extent to which brain edema contributes to pathology has not been investigated. Using the model of P. berghei ANKA infection, we compared brain microvessel morphology of CM-susceptible and CM-resistant mice. By quantitative planimetry, we provide evidence that CM is characterized by enlarged perivascular spaces (PVS). We show a dramatic aquaporin 4 (AQP4) upregulation, selectively at the level of astrocytic foot processes, in both CM and non-CM disease, but significantly more pronounced in mice with malarial-induced neurological syndrome. This suggests that a threshold of AQP4 expression is needed to lead to neurovascular pathology, a view that is supported by significantly higher levels in mice with clinically overt CM. Numbers of intravascular leukocytes significantly correlated with both PVS enlargement and AQP4 overexpression. Thus, brain edema could be a contributing factor in CM pathogenesis and AQP4, specifically in its astrocytic location, a key molecule in this mechanism. Since experimental CM is associated with substantial brain edema, it models paediatric CM better than the adult syndrome and it is tempting to evaluate AQP4 in the former context. If AQP4 changes are confirmed in human CM, it may represent a novel target for therapeutic intervention.
%Z FOR Codes: 60502


%0 Journal Article
%~ PubMed
%A Chan-Ling, Tailoi
%A Koina, Mark E
%A McColm, Janet R
%A Dahlstrom, Jane E
%A Bean, Elaine
%A Adamson, Sam
%A Yun, Steven
%A Baxter, Louise
%T Role of CD44+ stem cells in mural cell formation in the human choroid: evidence of vascular instability due to limited pericyte ensheathment.
%B Investigative Ophthalmology & Visual Science
%D 2011
%C United States
%I Association for Research in Vision and Ophthalmology
%V 52
%N 1
%P 399-410
%@ 0146-0404
%X To examine mural cell differentiation and pericyte ensheathment during human choroidal vascular formation and into adulthood.
%Z FOR Codes: 1113


%0 Book Section
%A Chan-Ling, Tailoi
%T Development of the Retinal Vasculature
%B Encyclopedia of the Eye
%D 2010
%C United Kingdom, Unit
%I Elsevier Ltd.
%V 
%N 
%P 22-34
%@ 9780123741981
%E Dartt, Darlene A
%E Besharse, Joseph C
%E Dana, Reza
%X 
%Z FOR Codes: 111303


%0 Journal Article
%~ PubMed
%A Howitt, Jason
%A Putz, Ulrich
%A Lackovic, Jenny
%A Doan, Anh
%A Dorstyn, Loretta
%A Cheng, Hong
%A Yang, Baoli
%A Chan-Ling, Tailoi
%A Silke, John
%A Kumar, Sharad
%A Tan, Seong-Seng
%T Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons.
%B Proceedings of the National Academy of Sciences
%D 2009
%C United States
%I National Academy of Sciences
%V 106
%N 36
%P 15489-15494
%@ 0027-8424
%X The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4-2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1(-/-) with Ndfip1(+/+) mice exposed to Fe reveals that Ndfip1(-/-) brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Chan-Ling, Tailoi
%A Chu, Yi
%A Baxter, Louise
%A Weible Ii, Michael
%A Hughes, Suzanne
%T In vivo characterization of astrocyte precursor cells (APCs) and astrocytes in developing rat retinae: Differentiation, proliferation, and apoptosis.
%B Glia
%D 2009
%C United States
%I John Wiley & Sons
%V 57
%N 1
%P 39-53
%@ 1098-1136
%X To characterize the timing of differentiation, antigenic expression, morphology, proliferative potential, and apoptosis during astrocyte differentiation in the rat retina in vivo.
%Z FOR Codes: 1113 111601


%0 Journal Article
%~ Isi
%A Kielczewski, J. L.
%A Jarajapu, Y. P. R.
%A McFarland, E. L.
%A Cai, J.
%A Afzal, A.
%A Calzi, S. L.
%A Chang, K. H.
%A Lydic, T.
%A Shaw, L. C.
%A Busik, J.
%A Hughes, J.
%A Cardounel, A. J.
%A Wilson, K.
%A Lyons, T. J.
%A Boulton, M. E.
%A Mames, R. N.
%A Chan-Ling, T.
%A Grant, M. B.
%T Insulin-Like Growth Factor Binding Protein-3 Mediates Vascular Repair by Enhancing Nitric Oxide Generation
%B Circulation Research
%D 2009
%C United States
%I Lippincott Williams & Wilkins
%V 105
%N 
%P 897-905
%@ 0009-7330
%X 
%Z FOR Codes: 110306


%0 Journal Article
%~ PubMed
%A Mansour, Hussein
%A Chamberlain, Coral G
%A Weible, Michael W
%A Hughes, Suzanne
%A Chu, Yi
%A Chan-Ling, Tailoi
%T Aging-related changes in astrocytes in the rat retina: Imbalance between cell proliferation and cell death reduces astrocyte availability.
%B Aging cell
%D 2008
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 7
%N 4
%P 526-40
%@ 1474-9726
%X The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats aged 3 (young adult) to 25 months (aged) were investigated qualitatively and quantitatively following immunofluorohistochemistry. Glial fibrillary acidic protein (GFAP), S100 and Pax2 were used to identify astrocytes, and blood vessels were localized using Griffonia simplicifolia isolectin B4. Cell proliferation was assessed by bromodeoxyuridine incorporation and cell death by TUNEL-labelling and immunolocalization of the apoptosis markers active caspase 3 and endonuclease G. The density and total number of parenchymal astrocytes in the retina increased between 3 and 9 months of age but decreased markedly between 9 and 12 months. Proliferation of astrocytes was detected at 3 months but virtually ceased beyond that age, whereas the proportion of astrocytes that were TUNEL positive and relative expression of active caspase 3 and endonuclease G increased progressively with aging. In addition, in aged retinas astrocytes exhibited gliosis-like morphology and loss of Pax2 reactivity. A small population of Pax2(+)/GFAP(-) cells was detected in both young adult and aged retinas. The reduction in the availability of astrocytes in aged retinas and other aging-related changes reported here may have a significant impact on the ability of astrocytes to maintain homeostasis and support neuronal function in old age.
%Z FOR Codes: 1109


%0 Journal Article
%~ Isi
%A Kuo, I. Y.
%A Chan-Ling, T.
%A Wojcikiewicz, R. J.
%A Hill, C. E.
%T Limited Intravascular Coupling in the Rodent Brainstem and Retina Supports a Role for Glia in Regional Blood Flow
%B Journal of Comparative Neurology
%D 2008
%C United States
%I John Wiley & Sons, Inc.
%V 511
%N 6
%P 773-787
%@ 0021-9967
%X 
%Z FOR Codes: 111301 110202


%0 Book Section
%A Chan-Ling, Tailoi
%T Vasculogenesis and Angiogenesis in Formation of the Human Retinal Vasculature
%B Retinal and Choroidal Angiogenesis
%D 2008
%C The Netherlands
%I Springer Netherlands
%V 
%N 
%P 119-138
%@ 978-1-4020-6779-2
%E Penn, J.S.
%X 
%Z FOR Codes: 1113


%0 Journal Article
%~ PubMed
%A Hughes, Suzanne
%A Gardiner, Tom
%A Baxter, Louise
%A Chan-Ling, Tailoi
%T Changes in pericytes and smooth muscle cells in the kitten model of retinopathy of prematurity: implications for plus disease.
%B Investigative ophthalmology & visual science
%D 2007
%C US
%I Association for Research in Vision and Ophthalmolo
%V 48
%N 3
%P 1368-1379
%@ 0146-0404
%X PURPOSE: Dilated and tortuous vessels (plus disease) in ROP is a grim prognostic indicator of visual outcome. The purpose of this study was to determine whether alterations in pericytes and smooth muscle cells (SMCs), are associated with the pathogenesis of ROP, including plus disease. METHODS: Kittens were exposed to either 4 (standard obliterative model) or 2 (modified model) days of hyperoxia, resulting in vaso-obliteration or localized vessel regression, respectively, and returned to room air. The modified model more closely resembles human ROP. Desmin and alpha-smooth muscle actin (SMA) immunohistochemistry and lectin labeling were used to label mural cells and vessels. The desmin ensheathment ratio (DER), a quantitative measure of vessel stability, was determined. RESULTS: In the neovasculature of the standard model and surviving vasculature of the modified model, radial arterioles and venules were dilated and SMCs attenuated. SMA expression on venules was decreased, and the difference in desmin expression normally observed between arterioles and venules was lost, indicating altered SMC differentiation. The DER was reduced in both ROP models, consistent with highly unstable vascular plexuses, receptive to angiogenic and vascular regression signals. CONCLUSIONS: The results provide compelling evidence of significant changes in arteriolar and venular SMCs in both experimental models of ROP. The delayed differentiation and apparent dedifferentiation of SMCs during the hypoxic phases would result in an impaired ability to regulate blood flow, contributing to the vasodilation and tortuosity, hallmarks of plus disease. Vessel tortuosity was seen only in the nonobliterative model, suggesting that tortuosity may be due to increased capillary resistance resulting from capillary closure.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Low, R S
%A Jones, A O
%A Houang, M
%A Newland, L
%A Morey, A L
%A Chan-Ling, T
%T Endometriosis of the inguinal region: magnetic resonance imaging (MRI) findings.
%B Australasian radiology
%D 2007
%C Australia
%I Blackwell Publishing Asia
%V 51 Suppl
%N 
%P B272-5
%@ 1440-1673
%X A case of endometrioma of the right inguinal canal region, diagnosed preoperatively, is presented. The diagnosis was made on the basis of cyclical symptoms relating to menstrual periods, in combination with demonstration of blood products within an enhancing focal lesion in the inguinal region with magnetic resonance imaging. The case presented here is unique, as it is the first case, to our knowledge, of an endometriotic lesion in the inguinal canal to demonstrate the characteristic ''shading sign'' at magnetic resonance imaging.
%Z FOR Codes:


%0 Journal Article
%~ Isi
%A Pan, H
%A Grant, MB
%A Sullivan, SM
%A Calzi, SL
%A Sengupta, N
%A Caballero, S
%A Chang, KH
%A Baxter, LC
%A Afzal, A
%A McFarland, EL
%A Chan-Ling, T
%A Shaw, LC
%T IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development
%B Proceedings of the National Academy of Sciences of the United States of America
%D 2007
%C US
%I National Academy of Sciences
%V 104
%N 25
%P 10595-10600
%@ 1091-6490
%X 
%Z FOR Codes: 110199


%0 Journal Article
%~ PubMed
%A Chan-Ling, Tailoi
%A Hughes, Suzanne
%A Baxter, Louise
%A Rosinova, Emelia
%A McGregor, Iain
%A Morcos, Yvette
%A van Nieuwenhuyzen, Petra
%A Hu, Ping
%T Inflammation and breakdown of the blood-retinal barrier during "physiological aging" in the rat retina: a model for CNS aging.
%B Microcirculation
%D 2007
%C United Kingdom
%I Informa Healthcare
%V 14
%N 1
%P 63-76
%@ 1073-9688
%X OBJECTIVE: To examine the possible contribution of inflammation and breakdown of the blood-brain barrier in the central nervous system (CNS) of physiologically aged rats showing cognitive decline. METHODS: Young (3- to 6-month-old) and aged (24- to 30-month-old) Wistar rats were assessed by the novel object recognition test. Vascular and inflammatory changes in the CNS were investigated in whole-mount preparations or sections of retinas from young adult or aged male Wistar rats. RESULTS: Aged rats showed a significant impairment in short-term memory compared with young adults. Deterioration of blood-retinal barrier function in aged rats was evidenced by leakage of intravascular tracer into the retinal parenchyma and reduced immunoreactivity for the tight junctional protein, occludin. Immunohistochemistry revealed the presence of major histocompatibility complex (MHC) class II-positive resident microglia, activated T cells, and monocyte-like cells in the retinal parenchyma of aged rats only. Microglia positive for the ED1 antigen, indicative of phagocytic activity, were also observed in these retinas. CONCLUSION: Breakdown of the blood-retinal barrier, MHC class II expression, microglial activation, and trafficking of activated T cells are associated with physiological aging. Such changes in the CNS may contribute to the pathogenesis of age-related cognitive decline.
%Z FOR Codes: 110904


%0 Journal Article
%~ PubMed
%A Weible, Michael W
%A Chan-Ling, Tailoi
%T Phenotypic characterization of neural stem cells from human fetal spinal cord: Synergistic effect of LIF and BMP4 to generate astrocytes.
%B Glia
%D 2007
%C United States
%I John Wiley & Sons, Inc
%V 55
%N 11
%P 1156-1168
%@ 0894-1491
%X If cell based therapy for spinal cord injury is to become a reality, greater insights into the biology of human derived spinal cord stem cells are a prerequisite. Significant species differences and regional specification of stem cells necessitates determining the effects of growth factors on human spinal cord stem cells. Fetal spinal cords were dissociated and expanded as neurospheres in medium with bone morphogenetic protein 4 (BMP4), leukemia inhibitory factor (LIF) or BMP4 and LIF. First-generation neurospheres comprised a heterogeneous population of neural cell types and after plating emergent cells included neurons, oligodendrocytes and GFAP(+) cells which coexpressed stem cells markers and those of the neuronal lineage and were thus identified as GFAP(+) neural precursor cells (NPC). When plated, neurospheres maintained in BMP4 demonstrated a reduced proportion of emergent oligodendrocytes from 13 to 4%, whereas LIF had no statistically significant effect on cell type distribution. Combining BMP4 and LIF reduced the proportion of oligodendrocytes to 3% and that of neurons from 37 to 16% while increasing the proportion of GFAP(+) NPC from 45 to 79%. After 10 passages in control media aggregates gave rise to multiple neural phenotypes and only continued passage of neurospheres in the presence of BMP4 and LIF resulted in unipotent aggregates giving rise to only astrocytes. These results provide a means of obtaining pure populations of human spinal-cord derived astrocytes, which could be utilized for further studies of cell replacement strategies or in vitro evaluation of therapeutics. (c) 2007 Wiley-Liss, Inc.
%Z FOR Codes: 110902


%0 Journal Article
%~ PubMed
%A Potter, Sarah M
%A Chan-Ling, Tailoi
%A Rosinova, Emilia
%A Ball, Helen J
%A Mitchell, Andrew J
%A Hunt, Nicholas H
%T A role for Fas-Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria.
%B Journal of Neuroimmunology
%D 2006
%C Netherlands
%I Elsevier BV
%V 173
%N 1-2
%P 96-107
%@ 0165-5728
%X Cerebral malaria (CM) kills more than 1 million children each year. Using a murine model of CM, we investigated the role of Fas-Fas ligand interactions in the neuropathogenesis of this disease. Lpr and Gld mice, deficient in Fas and Fas ligand, respectively, were protected from fatal CM, although they demonstrated some pathological features associated with CM in the wild type mouse. Fas-Fas ligand mRNA and protein expression were increased in the brain in mice with CM, and activated caspase-3-positive apoptotic astrocytes were observed. We suggest that Fas-mediated apoptosis of astrocytes is likely to be a critical factor in late-stage murine CM pathogenesis.
%Z FOR Codes: 110799


%0 Journal Article
%~ PubMed
%A Hughes, Suzanne
%A Gardiner, Tom
%A Hu, Ping
%A Baxter, Louise
%A Rosinova, Emelia
%A Chan-Ling, Tailoi
%T Altered pericyte-endothelial relations in the rat retina during aging: Implications for vessel stability.
%B Neurobiology of Aging
%D 2006
%C United States
%I Elsevier Inc.
%V 27
%N 12
%P 1838-1847
%@ 1558-1497
%X Mural cells (smooth muscle cells and pericytes) regulate blood flow and contribute to vessel stability. We examined whether mural cell changes accompany age-related alterations in the microvasculature of the central nervous system. The retinas of young adult and aged Wistar rats were subjected to immunohistofluorescence analysis of alpha-smooth muscle actin (SMA), caldesmon, calponin, desmin, and NG2 to identify mural cells. The vasculature was visualized by lectin histochemistry or perfusion of horse-radish peroxidase, and vessel walls were examined by electron microscopy. The early stage of aging was characterized by changes in peripheral retinal capillaries, including vessel broadening, thickening of the basement membrane, an altered length and orientation of desmin filaments in pericytes, a more widespread SMA distribution and changes in a subset of pre-arteriolar sphincters. In the later stages of aging, loss of capillary patency, aneurysms, distorted vessels, and foci of angiogenesis were apparent, especially in the peripheral deep vascular plexus. The capillary changes are consistent with impaired vascular autoregulation and may result in reduced pericyte-endothelial cell contact, destabilizing the capillaries and rendering them susceptible to angiogenic stimuli and endothelial cell loss as well as impairing the exchange of metabolites required for optimal neuronal function. This metabolic uncoupling leads to reactivation of "physiological hypoxia" and angiogenesis in CNS aging.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Chan-Ling, Tailoi
%A Baxter, Louise
%A Afzal, Aqeela
%A Sengupta, Nilanjana
%A Caballero, Sergio
%A Rosinova, Emilia
%A Grant, Maria B
%T Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization.
%B American journal of pathology
%D 2006
%C USA
%I American Society for Investigative Pathology
%V 168
%N 3
%P 1031-44
%@ 0002-9440
%X Vascular repair by adult hematopoietic stem cells (HSCs) is well-appreciated because these cells are known for their plasticity. We have shown that adult HSCs differentiate into endothelial cells and participate in both retinal and choroidal neovascularization. We asked whether HSCs participated in the wounding response by forming astrocytes, retinal pigment epithelia (RPE), macrophages, and pericytes. Lethally irradiated C57BL6/J mice were reconstituted with HSCs from mice homozygous for green fluorescent protein (GFP) and then subjected to laser-induced rupture of Bruch''s membrane. After immunohistochemical examination of ocular tissue, GFP(+) astrocytes were observed concentrated along the edge of the laser wound, where they and mural cells closely ensheathed the neovasculature. GFP(+) vascular endothelial cells and macrophages/microglia were also evident. Large irregularly shaped GFP(+) RPE cells constituted approximately 93% of RPE cells adjacent to the edge of the denuded RPE area. In regions farther away from the wound, GFP(+) RPE cells were integrated among the GFP(-) host RPE. Thus, postnatal HSCs can differentiate into cells expressing markers specific to astrocytes, macrophages/microglia, mural cells, or RPE. These studies suggest that HSCs could serve as a therapeutic source for long-term regeneration of injured retina and choroid in diseases such as age-related macular degeneration and retinitis pigmentosa.
%Z FOR Codes: 111301 110902 110904


%0 Journal Article
%~ PubMed
%A Hunt, Nicholas H
%A Golenser, Jacob
%A Chan-Ling, Tailoi
%A Parekh, Sapan
%A Rae, Caroline
%A Potter, Sarah
%A Medana, Isabelle M
%A Miu, Jenny
%A Ball, Helen J
%T Immunopathogenesis of cerebral malaria.
%B International Journal for Parasitology
%D 2006
%C United Kingdom
%I Elsevier Ltd.
%V 36
%N 5
%P 569-582
%@ 0020-7519
%X Malaria is one of the most important global health problems, potentially affecting more than one third of the world''s population. Cerebral malaria (CM) is a deadly complication of Plasmodium falciparum infection, yet its pathogenesis remains incompletely understood. In this review, we discuss some of the principal pathogenic events that have been described in murine models of the disease and relate them to the human condition. One of the earliest events in CM pathogenesis appears to be a mild increase in the permeability to protein of the blood-brain barrier. Recent studies have shown a role for CD8+T cells in mediating damage to the microvascular endothelium and this damage can result in the leakage of cytokines, malaria antigens and other potentially harmful molecules across the blood-brain barrier into the cerebral parenchyma. We suggest that this, in turn, leads to the activation of microglia and the activation and apoptosis of astrocytes. The role of hypoxia in the pathogenesis of cerebral malaria is also discussed, with particular reference to the local reduction of oxygen consumption in the brain as a consequence of vascular obstruction, to cytokine-driven changes in glucose metabolism, and to cytopathic hypoxia. Interferon-gamma, a cytokine known to be produced in malaria infection, induces increased expression, by microvascular endothelial cells, of the haem enzyme indoleamine 2,3-dioxygenase, the first enzyme in the kynurenine pathway of tryptophan metabolism. Enhanced indoleamine 2,3-dioxygenase expression leads to increased production of a range of biologically active metabolites that may be part of a tissue protective response. Damage to astrocytes may result in reduced production of the neuroprotectant molecule kynurenic acid, leading to a decrease in its ratio relative to the neuroexcitotoxic molecule quinolinic acid, which might contribute to some of the neurological symptoms of cerebral malaria. Lastly, we discuss the role of other haem enzymes, cyclooxygenase-2, inducible nitric oxide synthase and haem oxygenase-1, as potentially being components of mechanisms that protect host tissue against the effects of cytokine- and leukocyte-mediated stress induced by malaria infection.
%Z FOR Codes: 110803


%0 Journal Article
%~ PubMed
%A Potter, Sarah
%A Chan-Ling, Tailoi
%A Ball, Helen J
%A Mansour, Hussein
%A Mitchell, Andrew
%A Maluish, Linda
%A Hunt, Nicholas H
%T Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria.
%B International Journal for Parasitology
%D 2006
%C United Kingdom
%I Elsevier Ltd.
%V 36
%N 4
%P 485-496
%@ 0020-7519
%X 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, perforin-deficient (pfp-/-) mice. From days 5-6p.i. onwards there was a significant increase in mRNA for granzyme B and CD8, but not CD4, in brain tissue from PbA-infected C57BL/6 and pfp-/- mouse brains. Perforin mRNA was strongly increased in the brains of PbA-infected C57BL/6 mice on day 6p.i. Immunohistochemistry revealed increased perforin staining and elevated numbers of CD8(+) cells within the cerebral microvessels in PbA-infected C57BL/6 at days 5 and 6p.i. compared with uninfected animals. At day 6p.i., there were TUNEL-positive cells and activated caspase-3 positive cells of endothelial morphology in the CNS of PbA-infected C57BL/6 mice. The TUNEL-positive cells were greatly reduced in pfp-/- mice. These results suggest that CD8(+)T lymphocytes induce apoptosis of endothelial cells via a perforin-dependent process, contributing to the fatal pathogenic process in murine cerebral malaria.
%Z FOR Codes: 110803


%0 Journal Article
%~ Isi
%A Flynn, J. T.
%A Chan-Ling, T.
%T Retinopathy of prematurity: Two distinct mechanisms that underlie zone 1 and zone 2 disease.
%B American Journal of Ophthalmology
%D 2006
%C US
%I Elsevier Inc.
%V 142
%N 1
%P 46-59
%@ 0002-9394
%X 
%Z FOR Codes: