Abstract TP264: Effects of Intra- and Post-Ischemic Normobaric Oxygen Therapy on Long Term Outcomes After Focal Ischemic Stroke
Background: Several rodent studies have documented neuroprotection with normobaric oxygen (NBO) therapy in acute ischemic stroke. These prior studies have typically utilized transient middle cerebral artery occlusion (MCAO) models with intra-ischemic NBO delivery, and measured outcomes at early time frames (24-48 hours). The effects of intra-ischemic and post-reperfusion NBO on long-term outcomes are not clear.
Methods: Adult male Sprague-Dawley rats were subjected to right MCAO for 100 minutes and randomly assigned to one of 3 groups in blinded fashion: 30% inspired oxygen (Controls), or 100% oxygen starting 15 minutes after MCAO for either 85 minutes (Intra-ischemic NBO), or 165 minutes (Prolonged NBO, i.e. intra-ischemic plus post-reperfusion hyperoxia). Isofluorane anesthesia was maintained for 180 minutes in all groups. Arterial blood gases, BP and heart rate were monitored periodically. Pathological infarct volumes, body weight, immunohistochemistry (for microglial/astrocyte activation, and angiogenesis), and neurofunctional outcomes (forelimb placement test, body swing test and neuroscore), were quantified after 2 weeks by a blinded investigator.
Results: At 2 weeks, infarct volumes were significantly reduced with Intra-ischemic NBO (132±92 mm3 vs. Controls, 257±101 mm3, p<0.05), and tended to be reduced with Prolonged NBO (166±99 mm3). Intra-ischemic NBO significantly (p<0.05) improved outcomes for weight loss (0±0 grams vs. Controls, 52±55.8 grams), forelimb placement test (2.4±2.3 vs. Controls, 5.3±3.3) and body-swing test (18.6±1.1 vs. Controls, 25.1±4.2), but not neuroscore (1.3±1.2 vs. Controls, 1.4±0.5). These functional outcomes were not significantly different between Controls and the Prolonged NBO group. NBO therapy had no effect on angiogenesis markers. However, Intra-ischemic NBO clearly decreased the expression of Iba1, a marker of activated microglia, and GFAP, a marker of activated astrocytes.
Conclusions: Intra-ischemic NBO affords long-term neuroprotection. Prolonged NBO does not appear to induce neurotoxicity. These results have clinical implications for using NBO as a stroke neuroprotective strategy.
- © 2012 by American Heart Association, Inc.