Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro, and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia

Abstract

Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro, and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo. In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

Neuroprotective effects of hyperbaric oxygen (HBO) therapy on neuronal death induced by sciatic nerve transection in rat

“…Four weeks after nerve transection, each group of animals was divided into 2 subgroups: (A) in which rats ( n = 7) were euthanized with an intraperitoneal injection of overdose of sodium pentobarbital, and spinal cord segments of the sciatic nerve removed from vertebral column for biochemical analysis, (B) in which rats ( n = 7) were euthanized with an intraperitoneal injection of overdose of sodium pentobarbital, and spinal cord segments of the sciatic nerve and related dorsal root ganglions (ipsilateral L4 and L5 DRGs) removed for histopathological assessment and immunohistochemistry. The doses and treatment schedules were based on previous studies [ 29 – 31 ] and pilot experiments in our laboratory.…”

“…The beneficial effects can be attributed to some biological activities such as anti-oxidative [ 21 , 22 ], anti-inflammatory [ 23 , 24 ], and anti-apoptotic [ 25 , 26 ] properties. Also, it was documented that HBO increased oxygen supply [ 27 ] and improved neural metabolism [ 28 ] after ischemia, along with promoting thrombolysis [ 29 ]. Despite the neuroprotective effects of HBO therapy against various experimental models of neural injury and disease, no studies have been conducted on the influence of HBO on neural apoptosis after nerve transection.…”

Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke

“…Current strategies include the following. (1) Statins may open collaterals after stroke, preserve penumbra, and expand the time window of thrombolysis [ 102 , 103 ]. Ovbiagele et al evaluated the relationship between prestroke statin use and pretreatment angiographic collateral grade among patients with acute ischemic stroke, and they found that the statin-treated group had significantly higher collateral scores than the nonstatin users, suggesting an association between statin use and improved collateralization during acute stroke [ 104 ].…”

Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection

“…It turned out that HBOT increased the thrombolytic effect of r-tPA by 64%, while NBOT only by 39%, as compared to controls. 35 There was also one case report showing a multimodality approach of intravenous and intra-arterial r-tPA thrombolysis repeated HBOT (2.0 ATA, 90 minutes, started 6 hours after stroke onset) and hypothermia improved the symptoms in spinal cord infarction. 36 …”