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arrange (open windows) on a computer desktop so that they overlap each other, with the title bars visible
a small waterfall or series of small waterfalls
a succession of stages or operations or processes or units; "progressing in severity as though a cascade of genetic damage was occurring"; "separation of isotopes by a cascade of processes"
rush down in big quantities, like a cascade (同)cascade down
relating to or affected by ischemia (同)ischaemic

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/07 14:48:15」(JST)

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The ischemic (ischaemic) cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia (inadequate blood supply).^[1] This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the activation of chemicals produced during and after ischemia.^[2] The ischemic cascade usually goes on for two to three hours but can last for days, even after normal blood flow returns.^[3]

A cascade is a series of events in which one event triggers the next, in a linear fashion. Thus "ischemic cascade" is actually a misnomer, since in it events are not always linear: in some cases they are circular, and sometimes one event can cause or be caused by multiple events.^[4] In addition, cells receiving different amounts of blood may go through different chemical processes. Despite these facts, the ischemic cascade can be generally characterized as follows:

Lack of oxygen causes the neuron's normal process for making ATP for energy to fail.
The cell switches to anaerobic metabolism, producing lactic acid.
ATP-reliant ion transport pumps fail, causing the cell to become depolarized, allowing ions, including calcium (Ca⁺⁺), to flow into the cell.
The ion pumps can no longer transport calcium out of the cell, and intracellular calcium levels get too high.
The presence of calcium triggers the release of the excitatory amino acid neurotransmitter glutamate.
Glutamate stimulates AMPA receptors and Ca⁺⁺-permeable NMDA receptors, which open to allow more calcium into cells.
Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals, reactive oxygen species and calcium-dependent enzymes such as calpain, endonucleases, ATPases, and phospholipases in a process called excitotoxicity.^[5]^[6] Calcium can also cause the release of more glutamate.
As the cell's membrane is broken down by phospholipases, it becomes more permeable, and more ions and harmful chemicals flow into the cell.
Mitochondria break down, releasing toxins and apoptotic factors into the cell.
The caspase-dependent apoptosis cascade is initiated, causing cells to "commit suicide."
If the cell dies through necrosis, it releases glutamate and toxic chemicals into the environment around it. Toxins poison nearby neurons, and glutamate can overexcite them.
If and when the brain is reperfused, a number of factors lead to reperfusion injury.
An inflammatory response is mounted, and phagocytic cells engulf damaged but still viable tissue.
Harmful chemicals damage the blood–brain barrier.
Cerebral edema (swelling of the brain) occurs due to leakage of large molecules like albumins from blood vessels through the damaged blood brain barrier. These large molecules pull water into the brain tissue after them by osmosis. This "vasogenic edema" causes compression of and damage to brain tissue (Freye 2011; Acquired Mitochondropathy-A New Paradigm in Western Medicine Explaining Chronic Diseases).

Mitigation of effects

The fact that the ischemic cascade involves a number of steps has led doctors to suspect that neuroprotectants such as calcium channel blockers or glutamate antagonists could be produced to interrupt the cascade at a single one of the steps, blocking the downstream effects. Though initial trials for such neuroprotective drugs led many to be hopeful, until recently, human clinical trials with neuroprotectants such as NMDA receptor antagonists were unsuccessful.^{[citation needed]}

On October 7, 2003, a U.S. patent number 6630507 entitled "Cannabinoids as Antioxidants and Neuroprotectants" was awarded to the United States Department of Health and Human Services, based on research carried out at the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). This patent claims that cannabinoids are "useful in the treatment and prophylaxis of wide variety of oxidation associated diseases such as ischemia, inflammatory ... and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma..."^[7]^[8]

On November 17, 2011, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR part 404.7(a)(1)(i), the National Institutes of Health, Department of Health and Human Services, published in the Federal Register, that it is contemplating the grant of an exclusive patent license to practice the invention embodied in U.S. Patent 6,630,507, entitled “Cannabinoids as antioxidants and neuroprotectants” and PCT Application Serial No. PCT/US99/08769 and foreign equivalents thereof, entitled “Cannabinoids as antioxidants and neuroprotectants” [HHS Ref. No. E-287-1997/2] to KannaLife Sciences Inc., which has offices in New York, U.S. This patent and its foreign counterparts have been assigned to the Government of the United States of America. The prospective exclusive license territory may be worldwide, and the field of use may be limited to: The development and sale of cannabinoid(s) and cannabidiol(s) based therapeutics as antioxidants and neuroprotectants for use and delivery in humans, for the treatment of hepatic encephalopathy, as claimed in the Licensed Patent Rights.^[9]

References

^ "eMedicine - Stroke, Ischemic : Article by Joseph U Becker".
^ Stroke Center of the Washington University School of Medicine.
^ "Stroke: Hope Through Research: National Institute of Neurological Disorders and Stroke (NINDS)".
^ Hinkle JL, Bowman L (April 2003). "Neuroprotection for ischemic stroke". J Neurosci Nurs 35 (2): 114–8. doi:10.1097/01376517-200304000-00008. PMID 12795039.
^ Jill Conway. 2000. "Diseases at the Cellular Level Lecture Handout" and Inflammation and Repair Lecture Handout" University of Illinois College of Medicine. Retrieved on January 9, 2007.
^ "eMedicine - Acute Stroke Management : Article by Edward C Jauch".
^ US patent 6630507, Hampson, Aidan J.; Axelrod, Julius; Grimaldi, Maurizio, "Cannabinoids as antioxidants and neuroprotectants", issued 2003-10-07
^ U.S. Patent 6630507.
^ "Federal Register | Prospective Grant of Exclusive License: Development of Cannabinoid(s) and Cannabidiol(s) Based Therapeutics To Treat Hepatic Encephalopathy in Humans". Federalregister.gov. 2011-11-17. Retrieved 2012-08-13.

UpToDate Contents

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1. 虚血プレコンディショニングの定義および病因 definition and pathogenesis of ischemic preconditioning
2. 心臓の虚血性再潅流障害 ischemic reperfusion injury of the heart
3. 冬眠心筋の評価 evaluation of hibernating myocardium
4. 虚血プレコンディショニングの臨床的意義 clinical implications of ischemic preconditioning
5. 下肢末梢動脈疾患の症状を治療するための試験的治療 investigational therapies for treating symptoms of lower extremity peripheral artery disease

English Journal

Short- and long-term consequences of perinatal asphyxia: looking for neuroprotective strategies.

Herrera-Marschitz M1, Neira-Peña T, Rojas-Mancilla E, Morales P, Bustamante D, Leyton L, Gebicke-Haerter P.
Advances in neurobiology.Adv Neurobiol.2015;10:169-98. doi: 10.1007/978-1-4939-1372-5_9.
Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. A primary insult is first produced by the length of the time without oxygenation, leading to hypoxia/ischemia and death if oxygenation is not promptly established. A
PMID 25287541

Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

Chang AY1, Li FC2, Huang CW3, Wu JC2, Dai KY2, Chen CH2, Li SH4, Su CH2, Wu RW5.
Neurobiology of disease.Neurobiol Dis.2014 Nov;71:292-304. doi: 10.1016/j.nbd.2014.08.005. Epub 2014 Aug 12.
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Reduced uterine perfusion pressure induces hypertension in the pregnant mouse.

Intapad S1, Warrington JP1, Spradley FT1, Palei AC1, Drummond HA1, Ryan MJ1, Granger JP2, Alexander BT3.
American journal of physiology. Regulatory, integrative and comparative physiology.Am J Physiol Regul Integr Comp Physiol.2014 Oct 8. pii: ajpregu.00268.2014. [Epub ahead of print]
Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting p
PMID 25298513

Japanese Journal

抗凝固・抗血小板とアンチエイジング(第9回)動脈硬化巣における血小板の活性化 : エイジングとの関連について

倉林均
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NAID 40020179443

脳梗塞急性期の病態と治療のターゲット

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脳は虚血に対し大変脆弱であり，脳血流量低下のレベルに応じて種々の細胞機能障害が出現する．虚血開始後，虚血中心部から周辺部にかけて，虚血性脱分極，グルタミン酸やCa2+による興奮性細胞傷害，フリーラジカルなどによる酸化的傷害，二次的微小循環障害，炎症反応，アポトーシスという一連の反応が，カスケード的に進行する．また，虚血巣周辺部の外縁では，内在的保護機転も賦活化される．脳梗塞急性期には，虚血巣中心部 …
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