gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Article

Send article

Treatment of cerebral vasospasm after experimental subarachnoid hemorrhage using intracisternal heme-oxygenase-1(HO-1) fused to a arginine protein transporter domain

Meeting Abstract

Search Medline for

  • Tomoyuki Ogawa - Department of Neurosurgery, Heinrich-Heine University Düsseldorf, Germany
  • Daniel Hänggi - Department of Neurosurgery, Heinrich-Heine University Düsseldorf, Germany
  • Hans Jakob Steiger - Department of Neurosurgery, Heinrich-Heine University Düsseldorf, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1594

doi: 10.3205/10dgnc069, urn:nbn:de:0183-10dgnc0694

Published: September 16, 2010

© 2010 Ogawa et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective: Heme-oxygenase-1(HO-1) is a 32 kDa enzyme involved in heme-catabolism and cleaves heme to form biliverdin and carbon monoxide (CO). HO-1 is said to reduce the contractile effect of hemoglobin. A sequence of 11 consecutive arginine groups (11R) is one of the most effective protein transduction domains (PTD). As previously reported, we could successfully fuse 11R to heme-oxigenase-1 (HO-1). The current experiments focused on the transduction efficacy and antispastic therapeutic effect of 11R-HO-1 protein in cerebral arteries. This is the first study to examine the therapeutic effect of a PTD fused vasoactive protein in cerebral arteries.

Methods: To examine the transduction efficacy of 11R-HO-1 protein in cerebral arteries, we injected the protein into the cisterna magna of male Sprague-Dawley (S-D) rats weighting 350 to 450 g. 11R-HO-1 or saline was infused into the cisterna magna of male rats. Several hours after the injection, the animals were sacrificed; the brain stems were extracted and cut at 10 micrometer on the cryostat. Immunofluorescence staining using a monoclonal mouse HO-1 antibody was performed and fluorescence intensity was measured.

A rat double-hemorrhage model of SAH was also used to assess whether protein transduction of 11R-HO-1 prevents vasospasm in vivo (total 36 rats). 0.2 ml of autologous arterial blood was injected into the cisterna magna of male rats on day 0 and day 2. Six hours before euthanasia on day 7, saline, 11R-EGFP (enhanced green fluorescent protein) or 11R-HO-1 was injected into the cisterna magna of the rats. Basilar artery (BA) diameters were measured following histological processing.

Results: With the results of immunofluorescence staining, we could prove that 11R-EGFP as well as 11R-HO-1 protein were well transduced into the rat cerebral arteries. In addition to that, the result of the rat SAH model showed that 11R-HO-1 protein had a significant effect on attenuating cerebral vasospasm after subarachnoid hemorrhage (SAH). (BA diameters: Control group [SAH only] 272.25±17.25 micrometer, 11R-EGFP injection group 292.68±18.29 micrometer, 11R-HO-1 injection group 369.43±18.66 micrometer, p<0.05).

Conclusions: 11R-HO-1 can be effectively delivered into rat BA by transcisternal application, resulting in prevention of the cerebral vasospasm after experimental SAH. This result suggest that 11R-HO-1 protein transduction into cerebral arteries may provide a novel therapeutic approach of cerebral vasospasm after SAH.