Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Jones, Nicole M.; Kardashyan, Liubov; Callaway, Jennifer K.; Lee, Elizabeth M.; Beart, Philip M

doi:10.1203/pdr.0b013e31816d9117

Cited by 52 publications

(37 citation statements)

References 41 publications

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“…The extent of injury that occurred in the current study is consistent with previous studies using the Rice-Vannucci model [19][20][21], which causes permanent ischemia in the ipsilateral hemisphere of the brain and hypoxia, but no damage in the contralateral hemisphere. Here we observed injury in the ipsilateral hemisphere affecting various brain regions including cortex, hippocampus and striatum.…”

Section: Discussionsupporting

confidence: 91%

“…Many studies have demonstrated neuroprotective roles for HIF-1a which could be explained by the transcription of many HIF-1 target genes involved in various cellular adaptive processes such as changes in glucose transport and metabolism, angiogenesis and neurogenesis [20,23]. Hypoxic treatment can increase expression of HIF-1, HIF-1 target genes and PHD2 [17,32,33], and recently the protective actions of hypoxic preconditioning were shown to be dependent on HIF-1a [16].…”

Section: Discussionmentioning

confidence: 99%

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Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Chu

Jones

2015

Neurochem Res

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Hypoxia leads to activation of many cellular adaptive processes which are regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 consists of HIF-1α and HIF-1ß subunits and levels of HIF-1α protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1α and PHDs at various time points after hypoxia-ischemia (HI), using a neonatal rat model of HI brain injury. Sprague-Dawley rat pups (postnatal day 7) were anaesthetized and underwent right carotid artery occlusion and were then exposed to 6 % oxygen for 2.5 h at 37 °C. HI injured animals demonstrated a significant reduction in the size of the ipsilateral hemisphere, compared to sham controls. Protein analysis using western blotting and enzyme-linked immunosorbent assay showed that 24 h after HI, there was a significant increase in PHD3 protein and an increase of HIF-1α compared to controls. At the 72 h time point, there was a reduction in PHD3 protein, which appeared to relate to cellular loss. There were no changes in PHD1 or PHD2 protein levels after HI when compared to age-matched controls. Further studies are necessary to establish roles for the HIF-1 regulatory enzyme PHD3 in brain injury processes.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Chu

Jones

2015

Neurochem Res

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“…Because many studies have shown that the CoCl 2 preconditioning can reduce the ischemia/hypoxia injury in many fields [23,24], our study focused on tolerance time and the disappearance of PS in hypoxia preconditioning mice which were treated with CoCl 2 before hypoxia exposure. Through this study we further clarified the role of HIF-1 in hypoxia tolerance.…”

Section: Resultsmentioning

confidence: 99%

The Effects of CoCl2 on HIF-1α Protein under Experimental Conditions of Autoprogressive Hypoxia Using Mouse Models

Zhang

Wang

Meister

et al. 2014

IJMS

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It is well known that cobalt chloride (CoCl2) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl2 and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl2 group. Over-induction of HIF-1α by pretreatment with CoCl2 before hypoxia did not increase the hypoxia tolerance.

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“…Therefore, CoCl 2 induces a hypoxiamimicking response by impairing the binding of von Hippel-Lindau protein with HIF-1a (Yuan et al 2003) causing the stabilization of HIF-1a and preventing its degradation by the proteasome. CoCl 2 has been recently used for preconditioning treatment and protection against hypoxicischemic injury in neonatal rats (Jones et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Neuronal and Glial Alterations Due to Focal Cortical Hypoxia Induced by Direct Cobalt Chloride (CoCl2) Brain Injection

et al. 2009

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Ischemic brain injury is a dynamic process that involves oxidative stress, inflammation, and cell death, as well as activation of endogenous adaptive and regenerative mechanisms depending on activation of transcription factors such as hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF-1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2 injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2 microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2 microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24 h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342, TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin staining, and electron microscopy (EM) were performed. Immediately after 1 h post CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and cromathin condensation were observed by immunostaining and EM, respectively. Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin maximal reactivity were detected during 6-9 h. Ultrastructural alterations of morphology included edematous perinuclear cytoplasm, organelles and endoplasmic reticulum (RE) enlargement, mitochondrial swelling with increased matrix density, and deposits of electron-dense material. Neurons showed particular nuclear indentations. Astrocytes and oligodendrocytes presented alterations in both nuclei and RE with dilated lumen and altered mitochondrias, and all these ultrastructural changes became detectable at day 5. CoCl2 cortical injection mimics focal brain ischemia, inducing neuronal death and glial activation. This model brings the opportunity to develop focal ischemia in selected brain areas to study their functional consequences and potential pharmacological therapies for in vivo models of stroke.

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Long-Term Functional and Protective Actions of Preconditioning With Hypoxia, Cobalt Chloride, and Desferrioxamine Against Hypoxic-Ischemic Injury in Neonatal Rats

Cited by 52 publications

References 41 publications

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

The Effects of CoCl2 on HIF-1α Protein under Experimental Conditions of Autoprogressive Hypoxia Using Mouse Models

Neuronal and Glial Alterations Due to Focal Cortical Hypoxia Induced by Direct Cobalt Chloride (CoCl2) Brain Injection

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