Ischemic Preconditioning in 18- to 20-Month-Old Gerbils

Dowden, Jennifer; Corbett, Dale

doi:10.1161/01.str.30.6.1240

Cited by 62 publications

(10 citation statements)

References 51 publications

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“…With the different models in mind, it is important to note that in the relapsing-remitting model used in our studies, CMH did not just delay EAE progression in the short term, it strongly reduced clinical score both at the peak of disease activity and at all time-points examined thereafter for the duration of the experiment (7 weeks), resulting in a marked and significant reduction in long-term clinical score. This neuroprotective effect of hypoxic pre-conditioning is consistent with a growing number of studies in animal models of ischemic stroke, whereby exposure to mild hypoxia dramatically reduces the size of ischemic infarct [10, 34, 43]. Interestingly, recent studies have highlighted the therapeutic potential of intermittent hypoxic training (IHT) in a number of other experimental neuropathologies, including Alzheimer’s disease, spinal cord injury, epilepsy and ethanol withdrawal-induced stress, raising the notion of therapeutic potential for IHT [17, 19, 24, 31, 48].…”

Section: Discussionsupporting

confidence: 82%

“…In the study of ischemic stroke it is well established that pre-conditioning with mild hypoxia protects against the development of ischemic infarct [10, 34, 43]. Interestingly, several years ago, the Dore-Duffy lab demonstrated that hypoxic pre-conditioning may also protect against the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [8] In that study, chronic exposure of mice to 10% O 2 (chronic mild hypoxia, CMH) suppressed clinical severity of EAE, which correlated with reductions in both leukocyte adherence to cerebral blood vessels and their infiltration into the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels

Halder

Kant

Milner

2018

acta neuropathol commun

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While hypoxic pre-conditioning protects against neurological disease the underlying mechanisms have yet to be fully defined. As chronic mild hypoxia (CMH, 10% O2) triggers profound vascular remodeling in the central nervous system (CNS), the goal of this study was to examine the protective potential of hypoxic pre-conditioning in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and then determine how CMH influences vascular integrity and the underlying cellular and molecular mechanisms during EAE. We found that mice exposed to CMH at the same time as EAE induction were strongly protected against the development of EAE progression, as assessed both at the clinical level and at the histopathological level by reduced levels of inflammatory leukocyte infiltration, vascular breakdown and demyelination. Mechanistically, our studies indicate that CMH protects, at least in part, by enhancing several properties of blood vessels that contribute to vascular integrity, including reduced expression of the endothelial activation molecules VCAM-1 and ICAM-1, maintained expression of endothelial tight junction proteins ZO-1 and occludin, and upregulated expression of the leukocyte inhibitory protein laminin-111 in the vascular basement membrane. Taken together, these data suggest that optimization of BBB integrity is an important mechanism underlying the protective effect of hypoxic pre-conditioning.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels

Halder

Kant

Milner

2018

acta neuropathol commun

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“…Interestingly, experimental mice exposed to chronic hypoxia display a widespread, robust angiogenic response throughout the CNS, which acts to reduce the average distance between capillary and neuron (Kanaan et al 2006; LaManna et al 1992). As animals that are hypoxic pre-conditioned are subsequently protected from ischemic insults (Dowden and Corbett 1999; Miller et al 2001), this raises the interesting possibility that the hypoxic-induced angiogenic remodeling may account for some of this protection.…”

Section: Introductionmentioning

confidence: 99%

An angiogenic role for the α5β1 integrin in promoting endothelial cell proliferation during cerebral hypoxia

Welser-Alves¹,

Flier²,

Boroujerdi³

et al. 2012

Experimental Neurology

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Fibronectin is a critical regulator of vascular modelling, both in development and in the adult. In the hypoxic adult central nervous system (CNS), fibronectin is induced on angiogenic vessels, and endothelial cells show strong induction of the two fibronectin receptors α5β1 and αvβ3 integrins. In a previous study, we found that the αvβ3 integrin is dispensable for hypoxic-induced cerebral angiogenesis, but a role for the endothelial α5β1 integrin was suggested. To directly investigate the role of endothelial α5 integrin in cerebral angiogenesis, wild-type mice and mice lacking α5 integrin expression in endothelial cells (α5-EC-KO) were subject to hypoxia (8% O2) for 0, 2, 4, 7 or 14 days. Quantification of cerebral vessel density and endothelial-specific proteins claudin-5 and Glut-1 revealed that α5-EC-KO mice displayed an attenuated angiogenic response, which correlated with delayed endothelial proliferation. α5-EC-KO mice showed no defect in the ability to organize a cerebrovascular fibronectin matrix, and no compensatory increase in vascular αvβ3 integrin expression. Consistent with these findings, primary α5KO brain endothelial cells (BEC) in culture exhibited delayed growth and proliferation. Taken together, these studies demonstrate an important angiogenic role for the α5β1 integrin in promoting BEC proliferation in response to cerebral hypoxia.

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“…

One of the consequences of ischemia is a rapid simultaneous increase in the concentrations of several metabolites, including succinic acid (SA) and choline [3].

…”

mentioning

confidence: 99%

“…It is known that short-term hypoxia or ischemia may temporarily increase brain resistance to subsequent ischemic insult [1,2]. The mechanisms of this phenomenon, which was termed preconditioning, are not studied well.…”

mentioning

confidence: 99%

Study of the Effect of Preconditioning with Succinic Acid Salt of Choline (1:2) on the Disturbances of Energy Metabolism in the Brain during Ischemia by 31P NMR In vivo

Помыткин¹,

Семенова

2005

Dokl Biochem Biophys

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It is known that short-term hypoxia or ischemia may temporarily increase brain resistance to subsequent ischemic insult [1,2]. The mechanisms of this phenomenon, which was termed preconditioning, are not studied well.One of the consequences of ischemia is a rapid simultaneous increase in the concentrations of several metabolites, including succinic acid (SA) and choline [3]. A role of these metabolites as potential mediators of preconditioning is not studied.The purpose of this work was to study the role of metabolites, which concentration is increased during ischemia, in the protective effect of preconditioning. The levels of phosphates, which are the main players in the energy metabolism of brain, were studied by NMR spectroscopy in vivo in rats preconditioned with the model drug succinic acid salt of choline (1:2) (SSC) using the model of total ischemia.The dynamics of phosphates involved in energy metabolism during total brain ischemia was used as an assessment criterion of the preconditioning effect. This selection was based on the fact that a decrease in the brain energy status due to deficiency in the blood-transported energy substrates and oxygen, required for ATP synthesis, is the triggering mechanism in the development of injuries induced by the brain ischemia [4].Because NMR spectroscopy in vivo , is a noninvasive method, it excludes experimental artifacts associated with the extraction of brain tissues and provides continuous monitoring of parameters detected, such as phosphates [5].In this study we demonstrated that SSC, administered into animals as a preconditioning agent, decelerates a decrease in the concentration of energy-rich phosphates (ATP and creatine phosphate (CP)) and a decrease in energy status of rat brain during total ischemia. Therefore, SSC may be regarded a mediator of ischemic preconditioning.SSC (10% solution in saline; dose, 10 mg/kg body weight) was injected into male Wistar rats (the experimental group) daily for seven days. The control animals were injected with saline.The levels of phosphate metabolites (such as ATP, CP, inorganic phosphate (P i ), and phosphate monoesters (PME)) and intracellular pH were measured in animals narcotized with Nembutal on day 8 after the beginning of the experiment using in vivo 31 P NMR.Brain spectra were recorded in an NMR-spectrometer AM-400WB (Bruker) at a frequency of 161.98 MHz for 31 P nuclei using a sensor with a surface coil, which was constructed for NMR studies of rat brain in vivo [6]. The conditions of spectrum recording were described in [7].Total ischemia in rats was modeled immediately after measurement in the sensor of the NMR spectrometer by arresting the heart with the use of alternating current at 27 V. The current was applied for 4 min on a pair of needle electrodes fixed under the skin of the chest. The 31 P brain spectra were recorded in vivo at 1-min intervals starting from the first minute. Each spectrum was recorded for 1 min. Measurements were performed for 15 min.The spectrum processing is described in [7]. The levels...

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Ischemic Preconditioning in 18- to 20-Month-Old Gerbils

Cited by 62 publications

References 51 publications

Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels

Hypoxic pre-conditioning suppresses experimental autoimmune encephalomyelitis by modifying multiple properties of blood vessels

An angiogenic role for the α5β1 integrin in promoting endothelial cell proliferation during cerebral hypoxia

Study of the Effect of Preconditioning with Succinic Acid Salt of Choline (1:2) on the Disturbances of Energy Metabolism in the Brain during Ischemia by 31P NMR In vivo

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