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  • 1
    Online Resource
    Online Resource
    Robust effects of genetic background on responses to subarachnoid hemorrhage in mice
    SAGE Publications ; 2016
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 36, No. 11 ( 2016-11), p. 1942-1954
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 36, No. 11 ( 2016-11), p. 1942-1954
    Abstract: Outcome varies among patients with subarachnoid hemorrhage but known prognostic factors explain only a small portion of the variation in outcome. We hypothesized that individual genetic variations influence brain and vascular responses to subarachnoid hemorrhage and investigated this using inbred strains of mice. Subarachnoid hemorrhage was induced in seven inbred and a chromosome 7 substitution strain of mouse. Cerebral blood flow, vasospasm of the middle cerebral artery, and brain injury were assessed. After 48 h of subarachnoid hemorrhage, mice showed significant middle cerebral artery vasospasm that correlated positively with reduction in cerebral blood flow at 45 min. Mice also had increased neuronal injury compared to sham controls; A/J and C57BL/6 J strains represented the most and least severe, respectively. However, brain injury did not correlate with cerebral blood flow reduction at 45 min or with vasospasm at 48 h. Chromosome 7 substitution did not influence the degree of vasospasm or brain injury. Our data suggested that mouse genetic background influences outcome of subarachnoid hemorrhage. Investigations into the genetic factors causing these inter-strain differences may provide insight into the etiology of the brain damage following subarachnoid hemorrhage. These findings also have implications for animal modeling of disease and suggest that genetic differences may also modulate outcome in other cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X15612489
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 2
    Online Resource
    Online Resource
    Molecular Alterations in the Hippocampus after Experimental Subarachnoid Hemorrhage
    SAGE Publications ; 2014
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 34, No. 1 ( 2014-01), p. 108-117
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 34, No. 1 ( 2014-01), p. 108-117
    Abstract: Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2013.170
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 3
    Online Resource
    Online Resource
    Pharmacologic Reduction of Angiographic Vasospasm in Experimental Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis
    SAGE Publications ; 2012
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 32, No. 9 ( 2012-09), p. 1645-1658
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 32, No. 9 ( 2012-09), p. 1645-1658
    Abstract: Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of −1.74; 95% confidence interval −2.04 to −1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm 〉 3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm 〉 3 days after SAH may be preferable for preclinical models.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2012.57
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 4
    Online Resource
    Online Resource
    Role of perivascular and meningeal macrophages in outcome following experimental subarachnoid hemorrhage
    SAGE Publications ; 2021
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 41, No. 8 ( 2021-08), p. 1842-1857
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 41, No. 8 ( 2021-08), p. 1842-1857
    Abstract: The distribution and clearance of erythrocytes after subarachnoid hemorrhage (SAH) is poorly understood. We aimed to characterize the distribution of erythrocytes after SAH and the cells involved in their clearance. To visualize erythrocyte distribution, we injected fluorescently-labelled erythrocytes into the prechiasmatic cistern of mice. 10 minutes after injection, we found labelled erythrocytes in the subarachnoid space and ventricular system, and also in the perivascular spaces surrounding large penetrating arterioles. 2 and 5 days after SAH, fluorescence was confined within leptomeningeal and perivascular cells. We identified the perivascular cells as perivascular macrophages based on their morphology, location, Iba-1 immunoreactivity and preferential uptake of FITC-dextran. We subsequently depleted meningeal and perivascular macrophages 2 days before or 3 hours after SAH with clodronate liposomes. At day 5 after SAH, we found increased blood deposition in mice treated prior to SAH, but not those treated after. Treatment post-SAH improved neurological scoring, reduced neuronal cell death and perivascular inflammation, whereas pre-treatment only reduced perivascular inflammation. Our data indicate that after SAH, erythrocytes are distributed throughout the subarachnoid space extending into the perivascular spaces of parenchymal arterioles. Furthermore, meningeal and perivascular macrophages are involved in erythrocyte uptake and play an important role in outcome after SAH.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X20980296
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2039456-1
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