Acute cerebral ischemia infarction

An early in vivo study in the model of global forebrain ischemia in the gerbil showed that a selective agonist of A3AR, IB-MECA, acutely administered 15 min prior to ischemia, impaired post-ischemic blood flow, increased mortality and exacerbated the loss of hippocampal neurons (von Lubitz et al. 1994). IB-MECA administration 20 min prior to transient middle cerebral ischemia also resulted in a significant increase in infarct size(von Lubitz et al. 2001). 

Kollmar R., Frietsch T., Georgiadis D., et al. (2002) Early effects of acid-base management during hypothermia on cerebral infarct volume, edema, and cerebral blood flow in acute focal cerebral ischemia in rats. Anesthesiology 97, 868-874. 

It is known from animal models with global ischemia and traumatic brain injury that moderate hypothermia attenuates secondary brain damage by reducing cerebral ischemia and postischemic brain edema and preserving the blood-brainbarrier. Even though hypothermia has potent cerebroprotective effects after experimental focal ischemia, clinical studies on hypothermic therapy after MCA infarction were not available until recently. We performed a pilot study investigating the efficacy, feasibility, and safety of induced moderate hypothermia in the therapy of patients with acute, severe MCA infarction and increased ICP. 

Apoptosis is programed cell death and differs from necrosis in that it results in minimal inflammation and release of genetic material. Although necrosis is the predominant process that follows acute ischemia, apoptosis is important after more minor injury, particularly within the ischemic penumbra. Apoptosis is executed by the production, activation and action of caspases, which are protein-cleaving enzymes that dismantle cytoskeleton proteins and enzymes responsible for cellular repair (Zhang et al. 2004). Neurons are particularly susceptible to caspase-mediated cell death after cerebral ischemia, as demonstrated by the reduction in infarct size by caspase inhibitors in experimental models. 

Aortic arch dissection can cause profound hypotension, with global, and sometimes boundary zone, cerebral ischemia or focal cerebral ischemia if the dissection spreads up one of the neck arteries. Clues to this diagnosis are anterior chest or interscapular pain, along with diminished, unequal or absent arterial pulses in the arms or neck and a normal electrocardiogram, unlike acute myocardial infarction, acute aortic regurgitation and pericardial effusion. 

Many events occuring during and after cerebral ischemia are well known, but they are not known enough to fully elucidate the mechanisms of brain damage. Factors responsible for the extension of infarction into the penumbral zone include acidosis, edema formation, acute local inflammation, dissipative ion fluxes, calcium overload, glutamate excitotoxicity, free radical formation, nitric oxide overproduction and programmed cell death [2,13-16]. 

An understanding of the role of leukocytes and the mediators of inflammation in cerebral ischemia may have a very great impact on therapy. An increasing number of molecules are currently being investigated in animals for their possible effectiveness in human acute stroke. Treatments to induce neutropenia, to reduce infarct volume and improve functional outcome are under heavy study. One group of studies has focused on... 

Since the early 1980s, much effort has focused on animal models of acute and chronic neurodegeneration in search of therapeutics for stroke. Neuronal cell death follows strokes, acute ischemic insults, and chronic neurodegeneration, such as Parkinson s disease, Alzheimer s disease (AD), epilepsy, and Huntington s disease. Up to 80% of all strokes result from focal infarcts and ischemia in the middle cerebral artery (MCA), so the commonly used animal models for neuroprotection are produced by temporary or permanent occlusion of the MCA.5 Lesions of the MCA include occlusion by electrocoagulation, intraluminal monofilaments, photochemical effects, thrombosis, and endothelin-1, but all of these models necessitate studying reperfusion events and validating MCA occlusion by behavioral assessments. 

Fig. 4.12. Mismatch concept of diffusion lesion (smaller) and perfusion deficit (larger) in human territorial brain infarction. Acute MCA territory ischemia/oligemia with a smaller, centrally located diffusion disturbance showing the relationship between infarct core, ischemic penumbra and changes in DWI and PI. DWI, diffusion-weighted imaging PI, perfusion imaging ADC, apparent diffusion coefficient ATP, high energy phosphates MCA, middle cerebral artery...

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