Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion

Abstract

The usefulness of the administration of hyperbaric oxygen (HBO) in the treatment of acute focal cerebral ischemia remains debatable. A significant association exists between focal cerebral injury and an excessive release of extracellular dopamine (DA). In vivo microdialysis was used in the present study to examine the effect of HBO on DA release in the striatum during ischemia and reperfusion in rats. The histological changes occurring were also evaluated. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery (MCA) using a surgically placed intraluminal filament. Control rats (n=8) were subjected to 1 h of ischemia, whilst the study rats (n=8) were in addition treated with HBO (2.8 atmospheres of absolute pressure 100% O(2)) during ischemia. Both groups were returned to breathing room air at normal pressure during reperfusion. Microdialysis samples were continuously collected at 15 min intervals at 2 microl.min(-1). The [mean (SE)] increase in release of striatal DA attained significance after 30 min of occlusion of MCA [170 (24)%], and continued to increase [268 (26)% at 45 min] reaching a peak level at 60 min [672 (59)%] before returning to the baseline level during the late reperfusion phase. There was no significant change in the level of DA in HBO treated rats during the period of ischemia. A significant reduction in edema and neuronal shrinkage were observed by histological examination in HBO treated rats when compared to the control rats. The results showed that HBO, when administered during ischemia, offered significant neuroprotection in our experimental model of transient focal cerebral ischemia in the rat. The mechanism seems to imply, at least in part, a reduced level of DA.

Hyperbaric Oxygen Therapy of Cerebral Ischemia

“…Decreased neuronal shrinkage and edema as well as decreased necrotic damage have been described histologically in animals treated with HBO after ischemia [8, 10, 11, 13]. Also, recent studies have shown a nearly immediate protective effect on apparent diffusion coefficient on HBO treated rats during cerebral ischemia.…”

“…Timing of temporary occlusions ranged from 20 min [11] to 24 h [59]. Several studies used a model involving very early institution of HBO therapy, starting treatment immediately [7, 10, 11, 17 ]or within minutes [6, 14, 62, 67, 68 ]of ischemia. Improved survival, smaller infarct size, and better neurologic function were seen in the HBO-treated animals.…”

“…Most showed a benefit to animals treated with HBO. Models of stroke examined cerebral ischemia with and without reperfusion through either temporary [7, 10, 11, 13, 14, 16, 17,59,60,61,62,63,64,65] (table 2) or permanent [6, 49, 50,65,66,67,68] (table 3) occlusion of cerebral arteries. Timing of temporary occlusions ranged from 20 min [11] to 24 h [59].…”

Hyperbaric Oxygen for Stroke

“…Improved survival, function and behavior in HBO treated animals were also reported (2,3,5,6,9,10,11,13,14,15,16,17,18,19). Several of the studies used a model involving the nearly immediate institution of HBO, starting treatment immediately (2,9,13,20) or within minutes (8,11,12,14) of ischemia. In models more consistent with conditions in a clinical setting, however, HBO delayed until several hours after the beginning of ischemia was also been shown to be effective.…”

“…Decreased neuronal shrinkage and edema as well as decreased necrotic damage have been described histologically in animals treated with HBO after ischemia. (13,19,20,37) Additionally, and perhaps more importantly, far fewer neurons show evidence of having undergone subsequent apoptosis after ischemia in animals treated with HBO. (15,37,38) HBO exposures in the first few minutes or hours after ischemia must, therefore, effect a lasting physiologic change which interrupts the subsequent cell death cascade.…”