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Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage


Muroi, C; Fujioka, M; Mishima, K; Irie, K; Fujimura, Y; Nakano, T; Fandino, J; Keller, E; Iwasaki, K; Fujiwara, M (2014). Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage. Journal of Thrombosis and Haemostasis, 12(4):505-514.

Abstract

Background: Microthrombosis and reactive inflammation contribute to neuronal injury after sub- arachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions.
Objective: To investigate the effect of ADAMTS-13 in experi- mental SAH.
Methods: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 lL per 10 g of body weight of 100 lg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also com- pared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH.
Results: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A ten- dency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vaso- spasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time.
Conclusions: ADAMTS-13 may reduce neuronal injury after SAH by reducing micro- thrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.

Abstract

Background: Microthrombosis and reactive inflammation contribute to neuronal injury after sub- arachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions.
Objective: To investigate the effect of ADAMTS-13 in experi- mental SAH.
Methods: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 lL per 10 g of body weight of 100 lg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also com- pared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH.
Results: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A ten- dency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vaso- spasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time.
Conclusions: ADAMTS-13 may reduce neuronal injury after SAH by reducing micro- thrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurosurgery
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:ADAMTS13, mouse; cerebral vasospasm; microcirculation; subarachnoid hemorrhage; thrombosis
Language:English
Date:January 2014
Deposited On:18 Feb 2015 11:10
Last Modified:05 Apr 2016 18:54
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:1538-7933
Additional Information:This is the accepted version of the following article: Journal of Thrombosis and Haemostasis, Volume 12, Issue 4, pages 505–514, April 2014, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jth.12511/abstract
Publisher DOI:https://doi.org/10.1111/jth.12511

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