Published Online
on April 1, 2004

A more recent version of this article appeared on May 1, 2004

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Submitted on June 2, 2003
Revised on December 1, 2003
Accepted on January 21, 2004

Neuroprotection by Hyperbaric Oxygenation After Experimental Focal Cerebral Ischemia Monitored by MR-Imaging

Wolf-Ruediger Schäbitz MD; Holger Schade; Sabine Heiland PhD; Rainer Kollmar MD; Jürgen Bardutzky MD; Nils Henninger MD; Harald Müller MD; Ulrich Carl MD; Shinya Toyokuni MD, PhD; Clemens Sommer MD^*; and Stefan Schwab MD

From Departments of Neurology (W.R.S., H.S., R.K., J.B., S.S.) and Neuroradiology (S.H.), University of Heidelberg, Germany; Division of Neuropathology (H.M., C.S.), University of Ulm, Germany; Department of Radiology (U.C.), Diakonie Krankenhaus, Rottenburg, Germany; Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Japan.

^* To whom correspondence should be addressed. E-mail: clemens.sommer{at}medizin.uni-ulm.de.

Background--Hyperbaric oxygenation (HBO) after focal cerebral ischemia reduces infarct size and improves outcome when applied early after stroke. Here, we evaluated effects of HBO on permanent focal cerebral ischemia and applied magnetic resonance imaging (MRI) monitoring to study lesion evolution.

Methods--Rats underwent permanent middle cerebral artery occlusion (MCAO). Two hours later, animals were treated with HBO (100% O₂/2 atm; n=17) for 1 hour or treated with room air (n=17). Animals underwent serial MRI studies (DWI, PI, T2) beginning 90 minutes after MCAO. Neuroscore was assessed (5-point rating scale). Animals were euthanized and brains were 2,3,5-triphenyltetrazolium chloride (TTC)-stained for infarct volume calculation 120 hours after MCAO. Immunohistochemistry was performed with antibodies against c-FOS and 4-hydroxy-2-nonenal-modified proteins (HNE) to check for effects of oxidative stress caused by HBO treatment.

Results--HBO reduced infarct volume by 38% (P<0.001). As shown by MRI, neuroprotection began 5 hours after ischemia and remained effective for 5 days. The relative regional cerebral blood flow was not different between groups at 3.5 and 5 hours after occlusion. There was less neurological deficit in HBO-treated animals compared with controls (P<0.05). Lipid peroxidation of cerebral vessels after HBO treatment as measured by HNE staining and pattern of c-FOS induction were not significantly different between groups at 3.5 and 8 hours after ischemia.

Conclusion-As monitored by MRI HBO treatment reversed ischemic lesion size between 3 and 5 hours after ischemia and achieved a long-lasting neuroprotective effect without significant oxidative damage.

Key words: hyperbaric oxygenation • focal cerebral ischemia • MRI • lipid peroxidation • neuroprotection

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