Distribution of Fluorescent Whitening Agents as an Indicator of Domestic Wastewater

( Hayakawa Kazuhide ),( Ryouji Okumura ),( Hiroki Yamamoto ),( Manabu Fujiwara ) 한국하천호수학회 2005 생태와 환경 Vol.38 No.S

Distribution of Fluorescent Whitening Agents as an Indicator of Domestic Wastewater

Hayakawa, Kazuhide,Ryouji Okumura,Hiroki Yamamoto,Manabu Fujiwara 한국수생태학회(구 한국하천호수학회) 2005 생태와 환경 Vol.38 No.S

CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation

Hayakawa, Kazuhide,Pham, Loc-Duyen D,Seo, Ji Hae,Miyamoto, Nobukazu,Maki, Takakuni,Terasaki, Yasukazu,Sakadž,ić,, Sava,Boas, David,van Leyen, Klaus,Waeber, Christian,Kim, Kyu-Won,Arai, Ken,L SAGE Publications 2016 Journal of cerebral blood flow and metabolism Vol.36 No.4

<P> There are numerous barriers to white matter repair after central nervous system injury and the underlying mechanisms remain to be fully understood. In this study, we propose the hypothesis that inflammatory macrophages in damaged white matter attack oligodendrocyte precursor cells via toll-like receptor 4 signaling thus interfering with this endogenous progenitor recovery mechanism. Primary cell culture experiments demonstrate that peritoneal macrophages can attack and digest oligodendrocyte precursor cells via toll-like receptor 4 signaling, and this phagocytosis of oligodendrocyte precursor cells can be inhibited by using CD200-Fc to downregulate toll-like receptor 4. In an in vivo model of white matter ischemia induced by endothelin-1, treatment with CD200-Fc suppressed toll-like receptor 4 expression in peripherally circulating macrophages, thus restraining macrophage phagocytosis of oligodendrocyte precursor cells and leading to improved myelination. Taken together, these findings suggest that deleterious macrophage effects may occur after white matter ischemia, whereby macrophages attack oligodendrocyte precursor cells and interfere with endogenous recovery responses. Targeting this pathway with CD200 may offer a novel therapeutic approach to amplify endogenous oligodendrocyte precursor cell-mediated repair of white matter damage in mammalian brain. </P>

Age-Related Decline in Oligodendrogenesis Retards White Matter Repair in Mice

Miyamoto, Nobukazu,Pham, Loc-Duyen D.,Hayakawa, Kazuhide,Matsuzaki, Toshinori,Seo, Ji Hae,Magnain, Caroline,Ayata, Cenk,Kim, Kyu-Won,Boas, David,Lo, Eng H.,Arai, Ken American Heart Association, Inc. 2013 Stroke Vol.44 No.9

<P><B>Background and Purpose—</B></P><P>Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury.</P><P><B>Methods—</B></P><P>A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl<SUB>2</SUB> treatment to induce chemical hypoxic stress.</P><P><B>Results—</B></P><P>Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells.</P><P><B>Conclusions—</B></P><P>An age-related decline in cyclic AMP response element-binding protein–mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.</P>

Distribution of Fluorescent Whitening Agents as an Indicator of Domestic Wastewater

Okumura, Ryouji,Yamamoto, Hiroki,Fujiwara, Manabu,Hayakawa, Kazuhide The Korean Society of Limnology 2005 생태와 환경 Vol.38 No.S

The distributions of fluorescent whitening agents (FWA) in the water of the Yasu River and their tributaries flowing into Lake Biwa (Japan) were surveyed on winter and summer. The FWA fluxes had linear correlation with the corrected resident population in catchments of the tributaries of Yasu River. Therefore, the FWAs in the rivers come from domestic wastewater, and those fluxes in the tributaries depended on the human population of their catchments. As an application of the FWA indicating domestic wastewater, we could assess seasonal changes in the sources of dissolved organic matter in the tributaries.

Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury.

Seo, Ji Hae,Miyamoto, Nobukazu,Hayakawa, Kazuhide,Pham, Loc-Duyen D,Maki, Takakuni,Ayata, Cenk,Kim, Kyu-Won,Lo, Eng H,Arai, Ken American Society for Clinical Investigation 2013 The Journal of clinical investigation Vol.123 No.2

<P>Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.</P>

Crosstalk between oligodendrocytes and cerebral endothelium contributes to vascular remodeling after white matter injury

Pham, Loc‐,Duyen D.,Hayakawa, Kazuhide,Seo, Ji Hae,Nguyen, Minh‐,Nguyet,Som, Angel T.,Lee, Brian J.,Guo, Shuzhen,Kim, Kyu‐,Won,Lo, Eng H.,Arai, Ken Wiley Subscription Services, Inc., A Wiley Company 2012 GLIA Vol.60 No.6

<P><B>Abstract</B></P><P>After stroke and brain injury, cortical gray matter recovery involves mechanisms of neurovascular matrix remodeling. In white matter, however, the mechanisms of recovery remain unclear. In this study, we demonstrate that oligodendrocytes secrete matrix metalloproteinase‐9 (MMP‐9), which accelerates the angiogenic response after white matter injury. In primary oligodendrocyte cultures, treatment with the proinflammatory cytokine interleukin‐1β (IL‐1β) induced an upregulation and secretion of MMP‐9. Conditioned media from IL‐1β‐stimulated oligodendrocytes significantly amplified matrigel tube formation in brain endothelial cells, indicating that MMP‐9 from oligodendrocytes can promote angiogenesis <I>in vitro</I>. Next, we asked whether similar signals and substrates operate after white matter injury <I>in vivo</I>. Focal white matter injury and demyelination was induced in mice via stereotactic injection of lysophosphatidylcholine into corpus callosum. Western blot analysis showed that IL‐1β expression was increased in damaged white matter. Immunostaining demonstrated MMP‐9 signals in myelin‐associated oligodendrocytic basic protein‐positive oligodendrocytes. Treatment with an IL‐1β‐neutralizing antibody suppressed the MMP‐9 response in oligodendrocytes. Finally, we confirmed that the broad spectrum MMP inhibitor GM6001 inhibited angiogenesis around the injury area in this white matter injury model. In gray matter, a neurovascular niche promotes cortical recovery after brain injury. Our study suggests that an analogous oligovascular niche may mediate recovery in white matter. © 2012 Wiley Periodicals, Inc.</P>

Dual effects of carbon monoxide on pericytes and neurogenesis in traumatic brain injury

Choi, Yoon Kyung,Maki, Takakuni,Mandeville, Emiri T,Koh, Seong-Ho,Hayakawa, Kazuhide,Arai, Ken,Kim, Young-Myeong,Whalen, Michael J,Xing, Changhong,Wang, Xiaoying,Kim, Kyu-Won,Lo, Eng H Nature Publishing Group 2016 Nature medicine Vol. No.

<P>At low levels, carbon monoxide (CO) has physiological roles as a second messenger and neuromodulator(1,2). Here we assess the effects of CO in a mouse model of traumatic brain injury (TBI). Treatment with CO-releasing molecule (CORM)-3 reduced pericyte death and ameliorated the progression of neurological deficits. In contrast, although treatment with the radical scavenger N-tert-butyl-a-phenylnitrone (PBN) also reduced pericyte death, neurological outcomes were not rescued. As compared to vehicle-treated control and PBN-treated mice, CORM-3-treated mice showed higher levels of phosphorylated neural nitric oxide synthase within neural stem cells (NSCs). Inhibition of nitric oxide synthase diminished the CORM-3-mediated increase in the number of cells that stained positive for both the neuronal marker NeuN and 5-bromo-2'-deoxyuridine (BrdU; a marker for proliferating cells) in vivo, consequently interfering with neurological recovery after TBI. Because NSCs seemed to be in close proximity to pericytes, we asked whether cross-talk between pericytes and NSCs was induced by CORM-3, thereby promoting neurogenesis. In pericyte cultures that were undergoing oxygen and glucose deprivation, conditioned cell culture medium collected after CORM-3 treatment enhanced the in vitro differentiation of NSCs into mature neurons. Taken together, these findings suggest that CO treatment may provide a therapeutic approach for TBI by preventing pericyte death, rescuing cross-talk with NSCs and promoting neurogenesis.</P>

Oxidative Stress Interferes With White Matter Renewal After Prolonged Cerebral Hypoperfusion in Mice

Miyamoto, Nobukazu,Maki, Takakuni,Pham, Loc-Duyen D.,Hayakawa, Kazuhide,Seo, Ji Hae,Mandeville, Emiri T.,Mandeville, Joseph B.,Kim, Kyu-Won,Lo, Eng H.,Arai, Ken American Heart Association, Inc. 2013 Stroke Vol.44 No.12

<P><B>Background and Purpose—</B></P><P>White matter injury caused by cerebral hypoperfusion may contribute to the pathophysiology of vascular dementia and stroke, but the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that oxidative stress interferes with endogenous white matter repair by disrupting renewal processes mediated by oligodendrocyte precursor cells (OPCs).</P><P><B>Methods—</B></P><P>In vitro, primary rat OPCs were exposed to sublethal CoCl<SUB>2</SUB> for 7 days to induce prolonged chemical hypoxic stress. Then, OPC proliferation/differentiation was assessed. In vivo, prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in mice. Then, reactive oxygen species production, myelin density, oligodendrocyte versus OPC counts, and cognitive function were evaluated. To block oxidative stress, OPCs and mice were treated with the radical scavenger edaravone.</P><P><B>Results—</B></P><P>Prolonged chemical hypoxic stress suppressed OPC differentiation in vitro. Radical scavenging with edaravone ameliorated these effects. After 28 days of cerebral hypoperfusion in vivo, reactive oxygen species levels were increased in damaged white matter, along with the suppression of OPC-to-oligodendrocyte differentiation and loss of myelin staining. Concomitantly, mice showed functional deficits in working memory. Radical scavenging with edaravone rescued OPC differentiation, ameliorated myelin loss, and restored working memory function.</P><P><B>Conclusions—</B></P><P>Our proof-of-concept study demonstrates that after prolonged cerebral hypoperfusion, oxidative stress interferes with white matter repair by disrupting OPC renewal mechanisms. Radical scavengers may provide a potential therapeutic approach for white matter injury in vascular dementia and stroke.</P>