Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration

Zhen, Jun Li; Wang, Wei Ping; Zhou, Jing; Qu, Zheng; Fang, Hai; Zhao, Ran; Lu, Yan; Wang, Hong Chao; Zang, Hong

doi:10.1016/j.brainres.2014.03.032

Cited by 26 publications

(24 citation statements)

References 34 publications

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“…209 Seizures were prevented and the associated subdural hemorrhage was significantly less in IHT than in non-IHT rats. This antiepileptic effect of IHT was confirmed in a recent study by Zhen et al, 210 where IHT reduced the frequency and severity of seizures in rats with pilocarpine-induced epilepsy. This protection was associated with suppression of intracellular calcium overload and inhibition of neuronal apoptosis in the hippocampus.…”

Section: Iht Reduces Vrfssupporting

confidence: 65%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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Section: Iht Reduces Vrfssupporting

confidence: 65%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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“…These changes usually include neurochemical imbalance, neurodegeneration, modification of synapsis and reorganization of specific areas and brain regions (Houser, 1992;Beach et al, 1995;Bertram, 2013). Many of these alterations are rendered in the rodent pilocarpine model of TLE used in the present work (Wang et al, 2008b;Zhen et al, 2014). In addition, it has been reported that these changes induce depression in many patients suffering from epilepsy (Favale et al, 2003;Hamid and Kanner, 2013).…”

Section: Discussionmentioning

confidence: 90%

“…During this time, neuronal damage in hippocampus, cortex, amygdala and thalamus occurs (André et al, 2007). In a similar way to clinical epilepsy, this model has been reported to induce a sustained increase in cytosolic calcium, resulting in activation of the mitochondrial apoptosis pathway (Zhen et al, 2014). The aforementioned events along with an overproduction of reactive oxygen species (ROS) are believed to be involved in the neuronal death induced by pilocarpine insult (Liu et al, 2010).…”

Section: Introductionmentioning

confidence: 96%

Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats

Shiha

Cristóbal

Delgado

et al. 2015

Brain Research Bulletin

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“…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]. While our studies demonstrate protection if hypoxic treatment is started before EAE disease occurs, to our knowledge, no-one has yet examined the impact of CMH on established EAE.…”

Section: Discussionmentioning

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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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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Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration

Cited by 26 publications

References 34 publications

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats

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

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