C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia

Yang, Guangdie; Kitagawa, Kazuo; Matsushita, Kohji; Mabuchi, Takuma; Yagita, Yoshiki; Yanagihara, Takehiko; Matsumoto, Masayasu

doi:10.1016/s0006-8993(96)01453-9

Cited by 223 publications

(169 citation statements)

References 34 publications

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“…Our data confirmed that the wild-type C57BL/6 strain is significantly more susceptible to cerebral ischemia than other strains for reasons that are not well understood. [17][18][19][20] For example, infarcts in C57BL/6 mice are 7-fold larger than in 129J mice 17 and 9.6-fold larger than in mixed 129/Sv and C57BL/6 mice as shown in the present study, and there is also significantly higher susceptibility to ischemia in C57BL/6 mice compared with 129/Sv mice. 18 -20 It is possible that the use of the highly susceptible C57BL/6 mouse to serve as a control for the effects of ischemia in mismatched tPA-deficient mouse strains, eg, the mixed 129/Sv and C57Bl/6 strain in a previous study, 10 could in addition to the differences in the ischemia models, eg, without thrombosis 10 versus with thrombosis and cerebrovascular fibrin deposition (present study), account for differences in the results and data interpretation between the 2 studies.…”

Section: Discussionsupporting

confidence: 64%

“…[17][18][19][20] Fibrin deposition in ischemic brain can be precipitated by procoagulant transformation of brain microvascular endothelium, [21][22][23]25 formation of a platelet plug, or leukocyte-endothelial interactions during reperfusion. 27 Previous studies have established a link between ischemic brain injury and reduced antithrombotic mechanisms in brain microcirculation in the presence of major stroke risk factors.…”

Section: Discussionmentioning

confidence: 99%

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Tissue Plasminogen Activator (tPA) Deficiency Exacerbates Cerebrovascular Fibrin Deposition and Brain Injury in a Murine Stroke Model

Tabrizi

Wang

Seeds

et al. 1999

ATVB

118

105

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Abstract-Although the serine protease, tissue plasminogen activator (tPA), is approved by the US Food and Drug Administration for therapy to combat focal cerebral infarction, the basic concept of thrombolytic tPA therapy for stroke was challenged by recent studies that used genetically manipulated tPA-deficient (tPAϪ/Ϫ) mice, which suggested that tPA mediates ischemic neuronal damage. However, those studies were potentially flawed because the genotypes of tPAϪ/Ϫ and wild-type control mice were not entirely clear, and ischemic neuronal injury was evaluated in isolation of tPA effects on brain thrombosis. Using mice with appropriate genetic backgrounds and a middle cerebral artery occlusion stroke model with nonsiliconized thread, which does lead to microvascular thrombus formation, in the present study we determined the risk for cerebrovascular thrombosis and neuronal injury in tPAϪ/Ϫ and genetically matched tPAϩ/ϩ mice subjected to transient focal ischemia. Cerebrovascular fibrin deposition and the infarction volume were increased by 8.2-and 6.7-fold in tPAϪ/Ϫ versus tPAϩ/ϩ mice, respectively, and these variables were correlated with reduced cerebral blood flow up to 58% (PϽ0.05) and impaired motor neurological score by 70% (PϽ0.05). Our findings indicate that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action. In addition, our study emphasizes the importance of appropriate genetic controls in murine stroke research. (Arterioscler Thromb Vasc Biol.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Tissue Plasminogen Activator (tPA) Deficiency Exacerbates Cerebrovascular Fibrin Deposition and Brain Injury in a Murine Stroke Model

Tabrizi

Wang

Seeds

et al. 1999

ATVB

118

105

View full text Add to dashboard Cite

show abstract

“…Core temperature was kept at 36.5-37.5°C with a heating blanket. Forebrain ischemia was induced by clamping both common carotid arteries for a 20 min interval (Yang et al, 1997). Mice undergoing sham ischemia received the same surgical incisions and handling but without carotid artery occlusion.…”

Section: Methodsmentioning

confidence: 99%

Zinc Triggers Microglial Activation

Kauppinen

Higashi²,

Suh³

et al. 2008

J. Neurosci.

160

172

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Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-B (NF-B) reporter gene showed a severalfold increase in NF-B activity in response to 30 M zinc. Cultured mouse microglia exposed to 15-30 M zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-B activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-B. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

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“…In several studies of permanent suture-induced MCAo, C57BL/6 mice exhibit significantly larger infarct volumes than Sv129 69,70 and in global ischemia C57BL6 is more sensitive than BALBc and other strains. 71 Interestingly, in distal MCAo (see below), BALBc mice have larger strokes than C57BL/6 and Sv129 strains. [72][73][74] There are strain differences in arterial collaterals and sensitivity to excitotoxic cell death that may partially account for these differences.…”

Section: Mouse Mcaomentioning

confidence: 98%

Rodent models of focal stroke: Size, mechanism, and purpose

2005

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Summary: Rodent stroke models provide the experimental backbone for the in vivo determination of the mechanisms of cell death and neural repair, and for the initial testing of neuroprotective compounds. Less than 10 rodent models of focal stroke are routinely used in experimental study. These vary widely in their ability to model the human disease, and in their application to the study of cell death or neural repair. Many rodent focal stroke models produce large infarcts that more closely resemble malignant and fatal human infarction than the average sized human stroke. This review focuses on the mechanisms of ischemic damage in rat and mouse stroke models, the relative size of stroke generated in each model, and the purpose with which focal stroke models are applied to the study of ischemic cell death and to neural repair after stroke.

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C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia

Cited by 223 publications

References 34 publications

Tissue Plasminogen Activator (tPA) Deficiency Exacerbates Cerebrovascular Fibrin Deposition and Brain Injury in a Murine Stroke Model

Tissue Plasminogen Activator (tPA) Deficiency Exacerbates Cerebrovascular Fibrin Deposition and Brain Injury in a Murine Stroke Model

Zinc Triggers Microglial Activation

Rodent models of focal stroke: Size, mechanism, and purpose

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