31
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Hyperglycemia Induced Cerebral Hematoma Expansion is Mediated by Plasma Kallikrein

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hyperglycemia is associated with increased hematoma expansion and worse clinical outcomes following intracerebral hemorrhage. We demonstrate that cerebral hematoma expansion triggered by intracerebral infusion of autologous blood is increased in diabetic rats and mice, and this response is ameliorated by plasma kallikrein (PK) inhibition and deficiency, respectively. Both diabetes and hyperglycemia induced in nondiabetic rats increase hematoma expansion following intracerebral injection of purified PK, a response not observed with bradykinin, plasmin, or tissue plasminogen activator. This response is rapid, prevented by co-injection of the glycoprotein VI (GPVI) agonist convulxin, and mimicked by GPVI inhibition or deficiency. We show that PK binding to collagen and PK-mediated inhibition of collagen-induced platelet aggregation is enhanced by hyperglycemia. Hyperosmotic mannitol also increases hematoma expansion induced by blood and PK, and increases PK-mediated inhibition of platelet aggregation. These findings suggest that hyperglycemia increases cerebral hematoma expansion by PK-mediated osmotic-sensitive inhibition of hemostasis.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: not found
          • Article: not found

          Spontaneous intracerebral hemorrhage.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality.

            The aim of this study was to determine the 30-day mortality and morbidity of intracerebral hemorrhage in a large metropolitan population and to determine the most important predictors of 30-day outcome. We reviewed the medical records and computed tomographic films for all cases of spontaneous intracerebral hemorrhage in Greater Cincinnati during 1988. Independent predictors of 30-day mortality were determined using univariate and multivariate statistical analyses. The 30-day mortality for the 188 cases of intracerebral hemorrhage was 44%, with half of deaths occurring within the first 2 days of onset. Volume of intracerebral hemorrhage was the strongest predictor of 30-day mortality for all locations of intracerebral hemorrhage. Using three categories of parenchymal hemorrhage volume (0 to 29 cm3, 30 to 60 cm3, and 61 cm3 or more), calculated by a quick and easy-to-use ellipsoid method, and two categories of the Glasgow Coma Scale (9 or more and 8 or less), 30-day mortality was predicted correctly with a sensitivity of 96% and a specificity of 98%. Patients with a parenchymal hemorrhage volume of 60 cm3 or more on their initial computed tomogram and a Glasgow Coma Scale score of 8 or less had a predicted 30-day mortality of 91%. Patients with a volume of less than 30 cm3 and a Glasgow Coma Scale score of 9 or more had a predicted 30-day mortality of 19%. Only one of the 71 patients with a volume of parenchymal hemorrhage of 30 cm3 or more could function independently at 30 days. Volume of intracerebral hemorrhage, in combination with the initial Glasgow Coma Scale score, is a powerful and easy-to-use predictor of 30-day mortality and morbidity in patients with spontaneous intracerebral hemorrhage.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).

              Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001). GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.
                Bookmark

                Author and article information

                Journal
                9502015
                8791
                Nat Med
                Nature medicine
                1078-8956
                1546-170X
                10 January 2011
                23 January 2011
                February 2011
                1 August 2011
                : 17
                : 2
                : 206-210
                Affiliations
                [1 ]Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA. Department of Medicine, Harvard Medical School, 25 Shattuck Street Boston, Massachusetts, 02115, USA.
                [2 ]Department of Medicine, Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
                [3 ]ActiveSite Pharmaceuticals Inc., 1456 Fourth St., Unit C, Berkeley CA 94710.
                Author notes
                Corresponding author: Edward P Feener, PhD, Joslin Diabetes Center, 1 Joslin Place, Boston MA, 02215, Fax number: 617-309-2637, Telephone number: 617-309-2599, Edward.Feener@ 123456joslin.harvard.edu
                [4]

                These authors contributed equally to this work.

                Article
                nihpa259055
                10.1038/nm.2295
                3038677
                21258336
                981acf5f-a055-40a3-92df-6d412344c305

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Eye Institute : NEI
                Award ID: R01 EY019029-03 ||EY
                Categories
                Article

                Medicine
                Medicine

                Comments

                Comment on this article