%0 Journal Article
%T Early outcome and blood-brain barrier integrity after co-administered thrombolysis and hyperbaric oxygenation in experimental stroke
%A Dominik Michalski
%A Johann Pelz
%A Christopher Weise
%A Johannes Kacza
%A Johannes Boltze
%A Jens Grosche
%A Manja Kamprad
%A Dietmar Schneider
%A Carsten Hobohm
%A Wolfgang H£¿rtig
%J Experimental & Translational Stroke Medicine
%D 2011
%I BioMed Central
%R 10.1186/2040-7378-3-5
%X Rats (n = 109) underwent embolic middle cerebral artery occlusion or sham surgery. Animals were assigned to: Control, NBO (60-minute pure oxygen), HBO (60-minute pure oxygen at 2.4 absolute atmospheres), tPA, or HBO+tPA. Functional impairment was assessed at 4 and 24 hours using Menzies score, followed by intravenous application of FITC-albumin as a BBB permeability marker, which was allowed to circulate for 1 hour. Further, blood sampling was performed at 5 and 25 hours for MMP-2, MMP-9, TIMP-1 and TIMP-2 concentration.Mortality rates did not differ significantly between groups, whereas functional improvement was found for NBO, tPA and HBO+tPA. NBO and HBO tended to stabilize BBB and to reduce MMP-2. tPA tended to increase BBB permeability with corresponding MMP and TIMP elevation. Co-administered HBO failed to attenuate these early deleterious effects, independent of functional improvement.The long-term consequences of simultaneously applied tPA and both NBO and HBO need to be addressed by further studies to identify therapeutic potencies in acute stroke, and to avoid unfavorable courses following combined treatment.The repeated translational failures of preclinical approaches in acute ischemic stroke necessitate a more complex perspective of tissue salvaging and regeneration in experimental research [1], involving functional key-structures such as the blood-brain barrier (BBB) with the associated 'neurovascular unit' [2-5]. Thromboembolic models are considered to provide best comparability to the human pathophysiology, thus being of increasing interest [5,6]. Along with the growing knowledge on time-dependent BBB changes [7,8], matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) were proposed as mediators with deleterious effects in early phases, but also regenerative properties in subsequent phases [9,10]. The application of oxygen under normobaric (NBO) or hyperbaric (HBO) conditions was shown to be beneficial in experimental studies by decreasing inf
%U http://www.etsmjournal.com/content/3/1/5