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Animal Models of Cerebral Ischemia - Oren Zarif - Cerebral Ischemia

Writer's picture: Oren ZarifOren Zarif

Despite the high death toll associated with cerebral ischemia, research continues to reveal new ways to treat it. Animal models are a valuable tool for studying the mechanisms of injury, and their potential target sites for neuroprotection. The review presented here summarizes the advantages and disadvantages of various animal models of cerebral ischemia. Here, we'll consider a few of the most common methods for reducing mortality associated with this condition.

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A blockage or bleeding in an artery can lead to cerebral ischemia. The narrowing of the arteries makes them prone to blood clots, and a clot can block blood flow and cause brain damage. Another common cause of cerebral ischemia is a heart attack, which is typically accompanied by low blood pressure and insufficient oxygenation of the body's tissues. Untreated heart attacks also slow down blood flow and increase the risk of clot formation.

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In both mild and severe cases of cerebral ischemia, tissue loss is slow, lasting fifteen to thirty minutes. In severe cases, brain tissue may be completely destroyed. Severe cases result in a cerebral infarction, which is the most common type of ischemic stroke. The symptoms of brain ischemia can range from mild to severe, and last anywhere from a few seconds to a few minutes. For this reason, it is sometimes referred to as a transient ischemic attack.

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Neuroimaging is done to confirm the diagnosis and rule out other causes of the symptoms of cerebral ischemia. CT scans can be helpful in detecting the cause of cerebral ischemia, including intracerebral hemorrhage, epidural hematoma, and a rapidly growing tumor. During the first few hours after the stroke, CT scans may show subtle signs of large anterior circulation ischemia. These symptoms include effacement of the insular cortical ribbon, loss of gray-white junction, and a dense middle cerebral artery sign. However, smaller infarcts may only be detected with diffusion-weighted MRI, which is highly sensitive for early ischemia.

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Global cerebral ischemia occurs when the blood flow to the brain is significantly reduced. This condition is often triggered by a cardiac arrest, and symptoms of the ailment may be brief. However, if enough time passes before the brain is re-blooded, the damage may be permanent. Reperfusion may also be necessary to prevent brain tissue damage. It is possible to sustain some brain tissue through the reperfusion, but reperfusion may result in reperfusion injury.

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Two models have been developed for studying the effects of cerebral ischemia. The 4-VO model has been used most often as a reference, while the 2-VO model is used as a substitute. In both models, cerebral blood flow is decreased by 5% or less. Moreover, the 2-VO model can be used to simulate cerebral ischemia. Although there are differences between the four models, they show similar results. During the first phase of the ischemia, glucose and oxygen levels in the brain decrease to less than 5%.

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In the event that the patient has experienced an acute ischemic stroke, the first goal of treatment is to restore breathing and blood pressure. The second goal of treatment is to reduce pressure inside the brain. This can be done through surgery or mechanical removal of the clot. Mechanical clot removal can occur up to 24 hours after the onset of symptoms. Long-term treatments include aspirin and anticoagulants. This type of treatment can result in a more positive outcome.

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While there are a number of options for treatment of DCI, many patients will have to choose a treatment based on the severity of their hemorrhage. In patients with new onset DCI, the first-line therapy should be used. The second-line therapy, called "rescue therapy", is aimed at those patients whose first-line treatment is not sufficient to reverse the ischemia. The current standard of care is to monitor patients for signs and symptoms of DCI.

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The most common imaging techniques for assessing ischemia include computed tomography and ultrasonography. However, these two techniques lack the sensitivity to detect ischemia in the early stages. To overcome this problem, 18F-based positron emission tomography probes were developed that use nuclear medicine to detect metabolic derangements in the brain, such as mitochondrial complex I activity. This method is considered more reliable than any other neuroimaging technique, because it allows better differentiation of damaged regions during earlier stages of ischemia. Magnetic resonance imaging is also preferred over other neuroimaging techniques, as it requires no radioactive tracers.

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