Expression of induced nitric oxide synthase in amoeboid microglia in postnatal rats following an exposure to hypoxia

You, Y.; Kaur, Charanjit

doi:10.1016/s0304-3940(99)00967-2

Cited by 32 publications

(11 citation statements)

References 19 publications

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“…It has been reported that activated microglial cells in the white matter may contribute to perinatal brain injury [66] through the secretion or production of noxious substances. NO production in the corpus callosum in response to hypoxia was found to increase in the neonatal brain along with iNOS expression in AMC [16,67] . In vitro studies have shown that NO produced by AMC is highly damaging to the oligodendrocytes resulting in their lysis [68] .…”

Section: Nature Of Amcmentioning

confidence: 99%

From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

Kaur

Dheen

Ling

2007

Acta Pharmacologica Sinica

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Amoeboid microglial cells (AMC) in the developing brain are active macrophages. The macrophagic nature of these cells has been demonstrated by many methods, such as the localization of various hydrolytic enzymes and the presence of complement type 3 surface receptors in them. More importantly is the direct visualization of these cells engaged in the phagocytosis of degenerating cells at the ultrastructural level. Further evidence of them being active macrophages is the avid internalization of tracers administered by the intravenous or intraperitoneal routes in developing rats. The potential involvement of AMC in immune functions is supported by the induced expression of major histocompatibility complex class I and II antigens on them when challenged by lipopolysaccharide or interferon-γ. Immunosuppressive drugs, such as glucocorticoids and immune function-enhancing drugs like melatonin, affect the expression of surface receptors and antigens and the release of cytokines by AMC. Recent studies in our laboratory have shown the expression of insulin-like growth factors, endothelins, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and N-methyl-D-asparate receptors. This along with the release of chemokines, such as stromal derived factor-1a and monocyte chemoattractant protein-1, suggests multiple functional roles of AMC in early brain development.

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Section: Nature Of Amcmentioning

confidence: 99%

From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

Kaur

Dheen

Ling

2007

Acta Pharmacologica Sinica

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“…The pro-inflammatory and pro-survival factors we examined are microglial effectors that are known to respond to hypoxia/ischemia, including NO (Nakashima et al, 1995;Yamashita et al, 1995;You and Kaur, 2000;Park et al, 2002;Suk, 2004), interleukin-1-beta (IL-1b) (Sairanen et al, 1997;Zhang et al, 1998;Davies et al, 1999;Mabuchi et al, 2000;Kim et al, 2003;Suk, 2004;Clausen et al, 2005), tumor necrosis factor-alpha (TNFa) (Buttini et al, 1996;Botchkina et al, 1997;Uno et al, 1997;Gregersen et al, 2000;Dziewulska and Mossakowski, 2003;Suk, 2004), brain-derived neurotrophic factor (BDNF) , and glial cell line-derived neurotrophic factor (GDNF) (Lee et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines

Lai

Todd

2006

Glia

101

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The tetracycline derivatives minocycline (MINO) and doxycycline (DOXY) have been shown to be neuroprotective in in vivo and in vitro models of stroke. This neuroprotection is thought to be due to the suppression of microglial activation. However, the specific molecular parameters in microglia of the tetracyclines' effect are not understood. We subjected cultured rat microglial and neuronal cells to in vitro hypoxia and examined the effects of MINO and DOXY pre-treatments. Our data showed that MINO and DOXY protect against hypoxia-induced neuronal death by a mechanism dependent on regulation of microglial factors, but likely unrelated to regulation of microglial proliferation/viability. Both MINO and DOXY suppressed the hypoxic activation of ED-1, a marker for microglial activation. Morphological analyses of hypoxic microglia using the microglial marker Iba1 revealed that treatment with MINO and DOXY caused a higher percentage of microglia to remain in a non-activated state. MINO suppressed the hypoxic upregulation of pro-inflammatory agents nitric oxide (NO), interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha), while DOXY down-regulated only NO and IL-1beta. In contrast, the hypoxic activation of pro-survival/neuroprotective microglial proteins, such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), were unaffected by tetracycline treatments. Taken together, these results suggest that MINO and DOXY may provide neuroprotection against stroke by selectively down-regulating microglial toxic factors while maintaining functional pro-survival factors.

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“…In addition to trying to protect the homeostasis of the extracellular milieu, astrocytes maintain their ability to communicate with each other and with distant neurons through gap junctions that remain open during an ischemic injury (18). Consequently, proapoptotic substances such as iNOS, shown to be expressed in rat glial cells following ischemia (11,19,20), can diffuse to neighboring cells via this network and cause further damage.…”

mentioning

confidence: 99%

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

Askalan

deVeber

et al. 2006

Pediatr Res

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Variability in the expression of apoptotic and inflammatory mediators with time after an ischemic insult and their role in the expansion of cerebral infarcts are still controversial. This study examines DNA degradation and the expression of activated caspase-3 and iNOS, inducible nitric oxide (iNOS) in the human developing brain. Autopsy specimens from children with a neuropathologic diagnosis of focal ischemic infarct were included in the study. The specimens were classified based on the clinical history as acute (Ͻ24 h, n ϭ 5), subacute (24 -72 h, n ϭ 8), or old (Ͼ72 h, n ϭ 6) infarcts. Immunohistochemical staining for caspase-3, iNOS and TUNEL were then performed on all infarcts alongside age-matched controls. TUNEL staining was detected in regions of all infarcts. Expression of iNOS was significantly higher than that of caspase-3 in the penumbra of subacute infarcts (p ϭ 0.02). Glial fibrillary acidic protein and iNOS staining co-localized in the penumbra of acute and subacute infarcts. These results suggest that cell death continues to occur for more than 3 d post ischemic insult. Cell death in the penumbra of subacute infarcts is partially caspase-3 independent and may be attributed to nitric oxide. Astrocytes are a source of iNOS and may play a role in the evolution of pediatric brain injury days after the initial insult.

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Expression of induced nitric oxide synthase in amoeboid microglia in postnatal rats following an exposure to hypoxia

Cited by 32 publications

References 19 publications

From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines

Astrocytic-Inducible Nitric Oxide Synthase in the Ischemic Developing Human Brain

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