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      What Sequences on High-Field MR Best Depict Temporal Resolution of Experimental ICH and Edema Formation in Mice?

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          Abstract

          Background and Purpose. Pilot study to examine the use of T1-, T2-, and T2*-weighted images for evaluating hematoma size and extent of edema in mouse brain at high field. Methods. Following collagenase-induced intracerebral hemorrhage, nine mice were imaged at 4.7 T using T1-, T2-, and T2*-weighted images for hematoma and edema quantitation on days 1, 3, 10, and 21 after surgery. Values were compared with morphometric analysis of cryosections at the time of final MR imaging. Results. For hematoma quantitation, the Spearman correlation coefficient ( r) between T1 signal change and histology was 0.70 ( P < 0.04) compared with r = 0.61 ( P < 0.09) for T2*. The extent of perihematomal edema formation on cryosections was well reflected on T2 with r = 0.73 ( P < 0.03). Conclusions. Within the limits of our pilot study, MR imaging on 4.7 T appears to approximate the temporal changes in hematoma and edema sizes in murine ICH well, thus laying the groundwork for longitudinal studies on hematoma resorption and edema formation.

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          Most cited references28

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          Spontaneous intracerebral hemorrhage.

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            Mechanisms of brain injury after intracerebral haemorrhage.

            The past decade has resulted in a rapid increase in knowledge of mechanisms underlying brain injury induced by intracerebral haemorrhage (ICH). Animal studies have suggested roles for clot-derived factors and the initial physical trauma and mass effect as a result of haemorrhage. The coagulation cascade (especially thrombin), haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets. Human imaging has shown that many ICH continue to expand after the initial ictus. Rebleeding soon after the initial haemorrhage is common and forms the basis of a current clinical trial using factor VIIa to prevent rebleeding. However, questions about mechanisms of injuries remain. There are conflicting data on the role of ischaemia in ICH and there is uncertainty over the role of clot removal in ICH therapy. The next decade should bring further information about the underlying mechanisms of ICH-induced brain injury and new therapeutic interventions for this severe form of stroke. This review addresses our current understanding of the mechanisms underlying ICH-induced brain injury.
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              Citicoline treatment for experimental intracerebral hemorrhage in mice.

              Citicoline sodium (cytidine-5'-diphosphocholine) has been shown previously to reduce ischemic injury in focal central nervous system models. Intracerebral hemorrhage (ICH) appears to be associated with an area of edema and ischemic injury surrounding the hematoma that may be reduced by neuroprotective therapy. The present study was designed to test whether treatment with citicoline reduces ischemic injury and improves functional neurological outcome in an experimental model of ICH. In 68 Swiss albino mice (26 to 36 g), ICH was induced by collagenase injection into the caudate nucleus. Animals were randomized to receive either: citicoline 500 mg/kg or saline IP prior to collagenase and at 24 and 48 hours. Animals were rated on a 28-point neurological scale and sacrificed at 54 hours. The brains were sectioned, and the volume of hematoma, total lesion, and surrounding ischemic injury was determined. In terms of functional outcome, animals treated with citicoline had improved neurological outcome scores compared with placebo-treated animals: 10.4+/-2.0 versus 12.1+/-2.4 (P<0.01). Regarding ischemic injury, although there was no difference in the underlying hematoma volumes, animals treated with citicoline had a smaller surrounding volume of ischemic injury than placebo-treated animals: citicoline, 13.8+/-5.8 mm3 (10.8+/-4.3% of hemisphere); placebo, 17.0+/-7.1 mm3 (13.3+/-5. 1%) (P<0.05). In this animal model of ICH, treatment with citicoline significantly improved functional outcome and reduced the volume of ischemic injury surrounding the hematoma. This study supports a potential role for citicoline in clinical ICH treatment.
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                Author and article information

                Journal
                J Biomed Biotechnol
                J. Biomed. Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2012
                30 April 2012
                : 2012
                : 961461
                Affiliations
                1Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
                2Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
                3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
                4Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
                5Division of Endovascular Neurosurgery and Interventional Neuroradiology, Departments of Radiology and Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
                Author notes

                Academic Editor: Oreste Gualillo

                Article
                10.1155/2012/961461
                3351132
                22619500
                6ea4b8a5-1e47-4106-a55f-9197ffccfb41
                Copyright © 2012 Mingchang Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 January 2012
                : 27 February 2012
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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