Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model

Yang, Yang; Zhang, Kaiyuan; Yin, Xuntao; Lei, Xuejiao; Chen, Xuezhu; Ju, Wang; Quan, Yulian; Yang, Ling; Jia, Zhengcai; Chen, Qianwei; Xian, Jishu; Lu, Yong; Huang, Qianyi; Zhang, Xuan; Feng, Hua; Chen, Tunan

doi:10.1007/s12975-019-00739-2

Cited by 22 publications

(16 citation statements)

References 43 publications

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“…The brains were immediately removed and dissected into 5 parts: ipsilateral and contralateral basal ganglia and cortex. The cerebellum was used as the internal control [31]. Each part was weighed on an electronic analytical balance (APX-60, Denver Instrument, NY, USA) giving the wet weight (WW) and then dried at 100°C for 24 h to determine the dry weight (DW).…”

Section: Evaluation Of Brain Water Contentmentioning

confidence: 99%

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

Yang

Nowrangi

Liang

et al. 2020

J Neuroinflammation

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Background: Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinflammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that Dickkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH. Methods: Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1β in the brain. Results: The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated, at least partly, by the Kremen-1 and DVL-1 pathways. Conclusions: DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1-mediated inflammation, thereby ameliorating the short-and long-term sequelae after ICH.

show abstract

Section: Evaluation Of Brain Water Contentmentioning

confidence: 99%

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

Yang

Nowrangi

Liang

et al. 2020

J Neuroinflammation

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“…Minocycline is being investigated in the phase II clinical trials of Zhao et al (2011a), which shows that minocycline inhibited iron overload, reduced iron neurotoxicity and iron-induced brain injury after ICH, which can be regarded as a new treatment option of ICH. Yang et al (2020) shows that minocycline reduced the brain edema and hematoma volume, prevented iron accumulation, and protected brain from iron-induced injury in ICH minipig models. Several other iron chelators, including nitrilotriacetic acid, ethylenediaminetetraacetic acid, and clioquinol, are effective for treating ICH, as demonstrated in animal models (Wang et al, 2016;Kose et al, 2019).…”

Section: Iron Chelatorsmentioning

confidence: 90%

“…Wang et al (2016) found that in rat models, DFP could reduce iron contents after ICH, but it was found to be ineffective against brain edema and lipid ROS and failed to improve the outcome. Furthermore, some studies found that minocycline functions as an iron chelator and can reduce iron-induced neuronal cell death (Zhao et al, 2011a;Chang et al, 2017;Fouda et al, 2017;Yang et al, 2019Yang et al, , 2020. Minocycline is being investigated in the phase II clinical trials of Zhao et al (2011a), which shows that minocycline inhibited iron overload, reduced iron neurotoxicity and iron-induced brain injury after ICH, which can be regarded as a new treatment option of ICH.…”

Section: Iron Chelatorsmentioning

confidence: 99%

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Mechanism of Ferroptosis and Its Relationships With Other Types of Programmed Cell Death: Insights for Potential Interventions After Intracerebral Hemorrhage

et al. 2020

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“…The brains were immediately removed and dissected into 5 parts: ipsilateral and contralateral basal ganglia and cortex. The cerebellum was us as the internal control (31). Each part was weighed on an electronic analytical balance (APX-60, Denver Instrument, NY, USA) giving the wet weight (WW) and then dried at 100 °C for 24 h to determine the dry weight (DW).…”

Section: Evaluation Of Brain Water Contentmentioning

confidence: 99%

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

Yang

Nowrangi

Liang

et al. 2020

Preprint

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Background: Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinﬂammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that Dickkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH. Methods: Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1β in the brain. Results: The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated , at least partly, by the Kremen-1 and DVL-1 pathways. Conclusions: DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1 mediated inflammation, thereby ameliorating the short- and long-term sequelae after ICH.

show abstract

Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model

Cited by 22 publications

References 43 publications

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

Mechanism of Ferroptosis and Its Relationships With Other Types of Programmed Cell Death: Insights for Potential Interventions After Intracerebral Hemorrhage

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

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