Cerebral protection by hypoxic preconditioning in a murine model of focal ischemia-reperfusion

Miller, Brandon A.; Perez, Ronaldo; Shah, Aarti R.; Gonzales, Ernesto R.; Park, T. S.; Gidday, Jeffrey M.

doi:10.1097/00001756-200106130-00030

Cited by 125 publications

(134 citation statements)

References 29 publications

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“…In general, two types of animal models, WbHPC and single-organ HPC, have been described [1,[7][8][9][10][11] . Lu et al created a…”

Section: An Animal Model Of Whole-body Hypoxic Preconditioning (Wbhpc)mentioning

confidence: 99%

Hypoxic preconditioning in an autohypoxic animal model

Shao

2012

Neurosci. Bull.

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Abstract:Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that results in increased resistance to a subsequent episode of severe hypoxia/ischemia. In this article, we review recent research based on a mouse model of repeated exposure to autohypoxia. Pre-exposure markedly increases the tolerance to or protection against hypoxic insult, and preserves the cellular structure of the brain. Furthermore, the hippocampal activity amplitude and frequency of electroencephalogram, latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease, while spatial learning and memory improve. In the brain, detrimental neurochemicals such as free radicals are down-regulated, while beneficial ones such as adenosine are upregulated. Also, antihypoxia factor(s) and gene(s) are activated. We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades. A potential path for further research is the development of devices and pharmaceuticals acting on antihypoxia factor(s) and gene(s) for the prevention and treatment of hypoxia and related syndromes.

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“…In general, two types of animal models, WbHPC and single-organ HPC, have been described [1,[7][8][9][10][11] . Lu et al created a…”

Section: An Animal Model Of Whole-body Hypoxic Preconditioning (Wbhpc)mentioning

confidence: 99%

Hypoxic preconditioning in an autohypoxic animal model

Shao

2012

Neurosci. Bull.

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“…Chronic cerebral hypoxia (8% oxygen for 2 weeks) promotes an active and robust vascular remodeling response, which culminates in B50% increased vascular density across all areas of the central nervous system (CNS) (LaManna et al, 2004;Milner et al, 2008a). The value of this model is underscored by the finding that mice exposed to chronic cerebral hypoxia (hypoxic preconditioned) are subsequently protected from focal cerebral ischemia (Miller et al, 2001). In light of the obvious need for arteriogenesis as part of an effective remodeling response after ischemic stroke, and the interesting expression pattern of CD105 on angiogenic vessels, the object of this study was twofold: first, to determine if chronic hypoxia promotes the formation of new arterial vessels, and second, to determine if CD105 preferentially labels angiogenic endothelial cells during hypoxic-induced vascular remodeling.…”

Section: Introductionmentioning

confidence: 99%

Chronic Cerebral Hypoxia Promotes Arteriogenic Remodeling Events that can be Identified by Reduced Endoglin (CD105) Expression and a Switch in β1 Integrins

Boroujerdi

Welser-Alves

Tigges

et al. 2012

J Cereb Blood Flow Metab

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Chronic cerebral hypoxia leads to a strong vascular remodeling response, though little is known about which part of the vascular tree is modified, or whether this response includes formation of new arterial vessels. In this study, we examined this process in detail, analyzing how hypoxia (8% O 2 for 14 days) alters the size distribution of vessels, number of arteries/arterioles, and expression pattern of endoglin (CD105), a marker of angiogenic endothelial cells in tumors. We found that cerebral hypoxia promoted the biggest increase in the number of medium to large size vessels, and this correlated with increased numbers of alpha smooth muscle actin (a-SMA)-positive arterial vessels. Surprisingly, hypoxia induced a marked reduction in CD105 expression on brain endothelial cells (BECs) within remodeling arterial vessels, and these BECs also displayed an angiogenic switch in b1 integrins (from a6 to a5), previously described for developmental angiogenesis. In vitro, transforming growth factor (TGF)-b1 also promoted this switch of BEC b1 integrins. Together, these results show that cerebral hypoxia promotes arteriogenesis, and identify reduced CD105 expression as a novel marker of arteriogenesis. Furthermore, our data suggest a mechanistic model whereby BECs in remodeling arterial vessels downregulate CD105 expression, which alters TGF-b1 signaling, to promote a switch in b1 integrins and arteriogenic remodeling.

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“…In addition, hypoxic preconditioning also induces tolerance against focal transient (15) and permanent (16) cerebral ischemia in adult mice. These studies suggested that hypoxia-inducible factor-1 (HIF-1) 1 could be an important mediator of hypoxia-induced tolerance to ischemia (13,14,16).…”

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confidence: 99%

Brain Genomic Response following Hypoxia and Re-oxygenation in the Neonatal Rat

Bernaudin

Tang

Reilly

et al. 2002

Journal of Biological Chemistry

271

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Hypoxic preconditioning (8% O 2 , 3 h) produces tolerance 24 h after hypoxic-ischemic brain injury in neonatal rats. To better understand the ischemic tolerance mechanisms induced by hypoxia, we used oligonucleotide microarrays to examine genomic responses in neonatal rat brain following 3 h of hypoxia (8% O 2 ) and either 0, 6, 18, or 24 h of re-oxygenation. The results showed that hypoxia-inducible factor (HIF)-1-but not HIF-2-mediated gene expression may be involved in brain hypoxia-induced tolerance. Among the genes regulated by hypoxia, 12 genes were confirmed by real time reverse transcriptase-PCR as follows: VEGF, EPO, GLUT-1, adrenomedullin, propyl 4-hydroxylase ␣, MT-1, MKP-1, CELF, 12-lipoxygenase, t-PA, CAR-1, and an expressed sequence tag. Some genes, for example GLUT-1, MT-1, CELF, MKP-1, and t-PA did not show any hypoxic regulation in either astrocytes or neurons, suggesting that other cells are responsible for the up-regulation of these genes in the hypoxic brain. These genes were expressed in normal and hypoxic brain, heart, kidney, liver, and lung, with adrenomedullin, MT-1, and VEGF being prominently induced in brain by hypoxia. These results suggest that a number of endogenous molecular mechanisms may explain how hypoxic preconditioning protects against subsequent ischemia, and may provide novel therapeutic targets for treatment of cerebral ischemia.Impaired oxygen (hypoxia) or reduced blood flow (ischemia) to the brain is a major cause of morbidity and mortality in the perinatal period, often resulting in cognitive impairment, seizures, and other neurological disabilities. Although hypoxiaischemia animal models have increased our understanding of the processes leading to cell death, there are still no pharmacological treatments available to reduce cell death in ischemic neonatal brain.Interestingly, cells can be protected when a non-injurious hypoxic stress is performed several hours or days before a lethal hypoxic-ischemic stress (preconditioning). This phenomenon is called tolerance. Ischemic tolerance can be achieved in brain by several preconditioning sublethal stresses such as hypoxia (1-3), ischemia itself (4), hypothermia (5), hyperthermia (6), hyperbaric oxygenation (7), metabolic inhibitors (8), spreading depression (9), as well as cytokines (10, 11).As hypoxic preconditioning is non-invasive and reproducible, this model has been used to study the mechanisms protecting the brain against hypoxia-ischemia particularly in newborn rats (3,(12)(13)(14). In addition, hypoxic preconditioning also induces tolerance against focal transient (15) and permanent (16) cerebral ischemia in adult mice. These studies suggested that hypoxia-inducible factor-1 (HIF-1) 1 could be an important mediator of hypoxia-induced tolerance to ischemia (13,14,16). Indeed, hypoxic preconditioning induces expression of HIF-1␣ and its target genes in neonatal (14) and adult brain (16). In addition, desferrioxamine and cobalt chloride, two agents that activate HIF-1 (17), also induce tolerance against hypoxia-ischemia...

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Cerebral protection by hypoxic preconditioning in a murine model of focal ischemia-reperfusion

Cited by 125 publications

References 29 publications

Hypoxic preconditioning in an autohypoxic animal model

Hypoxic preconditioning in an autohypoxic animal model

Chronic Cerebral Hypoxia Promotes Arteriogenic Remodeling Events that can be Identified by Reduced Endoglin (CD105) Expression and a Switch in β1 Integrins

Brain Genomic Response following Hypoxia and Re-oxygenation in the Neonatal Rat

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