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      Relevance of Experimental Ischemia in Cats for Stroke Management: A Comparative Reevaluation

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          Repeat studies in animal models of acute focal ischemia can be compared to incidental studies in the course of ischemic stroke in order to shed light on the development of changes causing ischemic infarcts or recovery of critically perfused tissue. Positron emission tomography (PET) studies of regional cerebral blood flow, cerebral metabolic rate for oxygen, oxygen extraction fraction (OEF), cerebral metabolic rate of glucose and flumazenil (FMZ) binding in the cat middle cerebral artery occlusion (MCAO) model and in patients with acute ischemic hemispheric stroke were reviewed. After permanent MCAO, the development of ‘misery-perfused’ penumbral tissue and its centrifugal conversion into necrosis could be demonstrated, resembling focal pathophysiological changes in patients with ischemic attacks. In the experimental model and in vascular insults in humans, a chance of recovery existed if collateral perfusion developed spontaneously within the first hours. In transient MCAO, reperfusion was only effective in preventing infarction when it was initiated as long as misery perfusion persisted; in these cases tissue was salvaged and large infarcts did not develop. In the other instances when oxygen metabolism broke down, and an increased OEF was no longer seen, reperfusion even at levels above preocclusion had no effect, and large space-occupying infarcts developed. These experimental findings are comparable to the variable outcome after thrombolytic therapy; if reperfusion is achieved within the therapeutic window of tissue viability, large infarcts are prevented and complete or partial recovery can be achieved. In the experimental model of focal ischemia and in human stroke, FMZ can be utilized as a marker of neuronal integrity. If FMZ binding in the cortex is decreased below 4 times the mean value of white matter in the acute stage, permanent infarcts were observed on late CT/MRI; this irreversible damage could not be prevented by thrombolytic therapy. These results demonstrated that PET studies in suitable ischemia models in cats can help to explain various courses and diverging outcomes of acute ischemic stroke. Comparable findings from experimental ischemia and human stroke may affect the selection of appropriate therapeutic strategies.

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          Most cited references 7

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          MicroPET: a high resolution PET scanner for imaging small animals

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            Magnetic resonance imaging of acute stroke.

             S Warach,  A Baird (1998)
            In the investigation of ischemic stroke, conventional structural magnetic resonance (MR) techniques (e.g., T1-weighted imaging, T2-weighted imaging, and proton density-weighted imaging) are valuable for the assessment of infarct extent and location beyond the first 12 to 24 hours after onset, and can be combined with MR angiography to noninvasively assess the intracranial and extracranial vasculature. However, during the critical first 6 to 12 hours, the probable period of greatest therapeutic opportunity, these methods do not adequately assess the extent and severity of ischemia. Recent developments in functional MR imaging are showing great promise for the detection of developing focal cerebral ischemic lesions within the first hours. These include (1) diffusion-weighted imaging, which provides physiologic information about the self-diffusion of water, thereby detecting one of the first elements in the pathophysiologic cascade leading to ischemic injury; and (2) perfusion imaging. The detection of acute intraparenchymal hemorrhagic stroke by susceptibility weighted MR has also been reported. In combination with MR angiography, these methods may allow the detection of the site, extent, mechanism, and tissue viability of acute stroke lesions in one imaging study. Imaging of cerebral metabolites with MR spectroscopy along with diffusion-weighted imaging and perfusion imaging may also provide new insights into ischemic stroke pathophysiology. In light of these advances in structural and functional MR, their potential uses in the study of the cerebral ischemic pathophysiology and in clinical practice are described, along with their advantages and limitations.
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              Mapping the Ischaemic Penumbra with PET: Implications for Acute Stroke Treatment

              The ischaemic penumbra has been documented in the laboratory animal as a severely hypoperfused, non-functional, but still viable cortex surrounding the irreversibly damaged ischaemic core; with elapsing time, more penumbra gets recruited into the core, while tissue reperfusion is able to stop this deleterious process until a certain point in time. As saving the penumbra should improve clinical outcome, it should constitute the main target of acute stroke therapy. In a series of PET studies performed 5–18 h after stroke onset, we were able to (i) document, for the first time in man, the existence of tissue fulfilling operational criteria for penumbra in about one third of the cases; (ii) show that long-term neurological recovery is proportional to the volume of penumbra that eventually escapes infarction, and (iii) detect penumbral tissue as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in such cases. Mapping the penumbra in the individual patient with neuroimaging procedures should allow to formulate a pathophysiological diagnosis, and thus to design a rational management of the stroke patient and to improve the selection of candidates for therapeutic trials.

                Author and article information

                Cerebrovasc Dis
                Cerebrovascular Diseases
                S. Karger AG
                February 2001
                16 February 2001
                : 11
                : 2
                : 73-81
                Max-Planck-Institut für neurologische Forschung, Köln, Deutschland
                47616 Cerebrovasc Dis 2001;11:73–81
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 33, Pages: 9
                Original Paper


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