Focal Cerebral Ischemia: Mechanisms

Han, Hyung Soo; Yenari, Midori A.

doi:10.1007/0-387-25403-x_3

Cited by 3 publications

(3 citation statements)

References 89 publications

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“…Brain protection from hypothermia is associated with preserved metabolic stores, reduced blood flow, prevention of glutamate release, reduced generation of excitotoxins, improved cellular ion handling and pH balance, decreased inflammation, decreased apoptosis, and alterations in gene expression [16][17][18][19][20][21][22][23][24]. Activation of peripheral leukocytes and brain resident microglia also occurs after brain injury, and mild hypothermia has been shown to inhibit this activation [25,26].…”

Section: Mechanisms Of Neuroprotective Effects Of Hypothermia: Suppormentioning

confidence: 99%

Investigational Therapies for Ischemic Stroke: Neuroprotection and Neurorecovery

2011

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Stroke is one of the leading causes of death and disability worldwide. Current treatment strategies for ischemic stroke primarily focus on reducing the size of ischemic damage and rescuing dying cells early after occurrence. To date, intravenous recombinant tissue plasminogen activator is the only United States Food and Drug Administration approved therapy for acute ischemic stroke, but its use is limited by a narrow therapeutic window. The pathophysiology of stroke is complex and it involves excitotoxicity mechanisms, inflammatory pathways, oxidative damage, ionic imbalances, apoptosis, angiogenesis, neuroprotection, and neurorestoration. Regeneration of the brain after damage is still active days and even weeks after a stroke occurs, which might provide a second window for treatment. A huge number of neuroprotective agents have been designed to interrupt the ischemic cascade, but therapeutic trials of these agents have yet to show consistent benefit, despite successful preceding animal studies. Several agents of great promise are currently in the middle to late stages of the clinical trial setting and may emerge in routine practice in the near future. In this review, we highlight select pharmacologic and cell-based therapies that are currently in the clinical trial stage for stroke.

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Section: Mechanisms Of Neuroprotective Effects Of Hypothermia: Suppormentioning

confidence: 99%

Investigational Therapies for Ischemic Stroke: Neuroprotection and Neurorecovery

2011

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“…However, the widely held notion that hypothermia protects because lower temperatures slow metabolism is not completely accurate (Yenari et al 2004). Recent research has shown that hypothermia can alter a plethora of cell death and cell survival pathways including gene regulation resulting in the inhibition of apoptosis and inflammation (Han and Yenari 2005,Liu and Yenari 2007) and the upregulation of anti-apoptotic (Slikker et al 2001) or trophic factors (D'Cruz et al 2002). In fact, in some systems, hypothermia has been shown to upregulate a family of ‘cold shock proteins’ at temperatures between 25-33C (Han and Yenari 2007), which could potentially regulate cell survival at a proximal point in the cell death pathway(s).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have shown that brain protection from hypothermia is associated with preserved metabolic stores, reduced blood flow, reduced generation of excitotoxins, decreased inflammation, decreased apoptosis and alterations in gene expression (Han and Yenari 2005,Liu and Yenari 2007,Zhao et al 2007). About 5% of the oxygen and glucose consumption are reduced per degree centigrade when the brain is cooled.…”

Section: Introductionmentioning

confidence: 99%

Hypothermia as a cytoprotective strategy in ischemic tissue injury

Tang¹,

Yenari²

2010

Ageing Research Reviews

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Hypothermia is a well established cytoprotectant, with remarkable and consistent effects demonstrated across multiple laboratories. At the clinical level, it has recently been shown to improve neurological outcome following cardiac arrest and neonatal hypoxia ischemia. It is increasingly being embraced by the medical community, and could be considered an effective neuroprotectant. Conditions such as brain injury, hepatic encephalopathy and cardiopulmonary bypass seem to benefit from this intervention. It's role in direct myocardial protection is also being explored. A review of the literature has demonstrated that in order to appreciate the maximum benefits of hypothermia, cooling needs to begin soon after the insult, and maintained for relatively long period periods of time. In the case of ischemic stroke, cooling should ideally be applied in conjunction with the reestablishment of cerebral perfusion. Translating this to the clinical arena can be challenging, given the technical challenges of rapidly and stably cooling patients. This review will discuss the application of hypothermia especially as it pertains to its effects neurological outcome, cooling methods, and important parameters in optimizing hypothermic protection.

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