Hyperbaric Oxygen as Stroke Therapy

Hyperbaric Oxygenation as an Adjunct Therapy in Strokes Due to Thrombosis
A Review of 122 Patients
RICHARD A. NEUBAUER, M.D. AND EDGAR END, M.D.
SUMMARY Results are reported using hyperbaric oxygenation (HBO) in 122 patients with strokes due to
thrombosis, both acute and completed. HBO is used as adjunctive treatment and there appears to be justification for a controlled study to delineate the treatment further. The authors beliere it is essential to treat patients with stroke at 1.5 to 2 atmospheres absolute (ATA).
(Stroke, Vol 11, No 3, 1980)




Hyperbaric Oxygen Reduces Neuronal Death and Improves
Neurological Outcome After Canine Cardiac Arrest
Robert E. Rosenthal, MD; Robert Silbergleit, MD; Patrick R. Hof, MD; Yolanda Haywood, MD; Gary Fiskum, PhD
Background and Purpose—Studies suggest that hyperbaric oxygen (HBO) is neuroprotective after experimental cerebral ischemia, but the mechanism is unknown. This study tested the hypotheses that postischemic HBO affords clinical and histopathological neuroprotection after experimental cardiac arrest and resuscitation (A/R) and that this neuroprotection results from improved cerebral oxygen metabolism after A/R.
Methods—Anesthetized adult female beagles underwent A/R and randomization to HBO (2.7-atm absolute [ATA] for 60 minutes, 1 hour after A/R) or control (PO2 80 to 100 mm Hg; 1 ATA). Animals underwent neurological deficit scoring (NDS) 23 hours after A/R. After euthanasia at 24 hours, neuronal death (necrotic and apoptotic) in representative animals was determined stereologically in hippocampus and cerebral neocortex. In experiment 2, arterial and sagittal sinus oxygenation and cerebral blood flow (CBF) were measured. Cerebral oxygen extraction ratio (ERc), oxygen delivery (DO2c), and metabolic rate for oxygen (CMRO2) were calculated (baseline and 2, 30, 60, 120, 180, 240, 300, and 360 minutes after restoration of spontaneous circulation).
Results—NDS improved after A/R in HBO animals (HBO, 35 14; controls, 54 15; P 0.028). Histopathological examination revealed significantly fewer dying neurons in HBO animals; the magnitude of neuronal injury correlated well with NDS. HBO corrected elevations in ERc (peak, 60 14% for controls, 26 4% for HBO) but did not increase DO2c or CMRO2, which decreased 50% after A/R in both groups.
Conclusions—HBO inhibits neuronal death and improves neurological outcome after A/R; the mechanism of HBO neuroprotection is not due to stimulation of oxidative cerebral energy metabolism. (Stroke. 2003;34:1311-1316.)




Hyperbaric Oxygen Reduces Tissue Hypoxia and Hypoxia-Inducible Factor-1 Expression in Focal Cerebral Ischemia
Li Sun, MD; Hugo H. Marti, MD; Roland Veltkamp, MD
Background and Purpose—The usefulness of hyperbaric oxygen (HBO) and normobaric hyperoxia in acute ischemic stroke is being reexplored because both improve outcome in experimental cerebral ischemia. However, even the basic mechanisms underlying oxygen therapy are poorly understood. We investigated the effect of both oxygen therapies on tissue hypoxia and on the transcription factor hypoxia-inducible factor-1 .
Methods—Mice were subjected to filament-induced middle cerebral artery occlusion for 2 hours. Twenty-five minutes after filament introduction, mice breathed normobaric air, normobaric 100% O2 (normobaric hyperoxia), or 100% O2 at 3 ata (HBO) for 95 minutes. Hypoxic regions were mapped on tissue sections after preischemic infusion of the in vivo hypoxia marker EF-5. Hypoxia-inducible factor-1 protein was measured after 2-hour middle cerebral artery occlusion using immunofluorescence and immunoblotting. Vascular endothelial growth factor expression was analyzed using in situ mRNA hybridization.
Results—Severity of ischemia did not differ among groups. HBO (35.2 10.4 mm2) significantly reduced the area of EF-5-stained hypoxic regions in focal cerebral ischemia compared with normobaric hyperoxia (46.4 11.2 mm2) and air (49.1 8 mm2, P 0.05, analysis of variance). Topographically, EF-5 fluorescence was decreased in medial striatum and in cortical ischemic border areas. Immunohistochemistry and immunoblotting revealed lower hypoxia-inducible factor-1 protein in the ischemic hemisphere of HBO-treated mice. Moreover, mRNA in situ hybridization showed
lower expression of vascular endothelial growth factor in HBO and normobaric hyperoxia groups.
Conclusions—Measurement of extrinsic and intrinsic markers of hypoxia revealed that HBO improves penumbral oxygenation in focal ischemia. Modification of the transcription factor hypoxia-inducible factor-1 and its downstream targets may be involved in effects of HBO.
(Stroke. 2008;39:1000 –1006.)