Hyperbaric Oxygen Reduces Neuronal Death and Improves Neurological Outcome After Canine Cardiac Arrest

George Washington University, Washington, Washington, D.C., United States
Stroke (Impact Factor: 5.72). 06/2003; 34(5):1311-6. DOI: 10.1161/01.STR.0000066868.95807.91
Source: PubMed

ABSTRACT 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.
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).
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 approximately 50% after A/R in both groups.
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.

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    • "However, Rosenthal et al. (2003) using the animal cardiac arrest model showed no increase in cerebral oxygen delivery and consumption during hyperbaric treatment. It was suggested that probably there is no ongoing ischemia during postischemic hypoperfusion and that energy metabolism may not be limited by oxygen delivery but rather by the activity of aerobic metabolic enzymes (McKinley et al. 1996; Rosenthal et al. 2003). Hyperbaric reduction in blood–brain barrier damage preventing inflammatory processes and inhibition of neutrophil adhesion to the endothelium are also factors which may contribute in neuronal protection (Buras and Reenstra 2007; Veltkamp et al. 2005). "
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    ABSTRACT: Anoxic brain injury resulting from cardiac arrest is responsible for approximately two-thirds of deaths. Recent evidence suggests that increased oxygen delivered to the brain after cardiac arrest may be an important factor in preventing neuronal damage, resulting in an interest in hyperbaric oxygen (HBO) therapy. Interestingly, increased oxygen supply may be also reached by application of normobaric oxygen (NBO) or hyperbaric air (HBA). However, previous research also showed that the beneficial effect of hyperbaric treatment may not directly result from increased oxygen supply, leading to the conclusion that the mechanism of hyperbaric prevention of brain damage is not well understood. The aim of our study was to compare the effects of HBO, HBA and NBO treatment on gerbil brain condition after transient forebrain ischemia, serving as a model of cardiac arrest. Thereby, we investigated the effects of repetitive HBO, HBA and NBO treatment on hippocampal CA1 neuronal survival, brain temperature and gerbils behavior (the nest building), depending on the time of initiation of the therapy (1, 3 and 6 h after ischemia). HBO and HBA applied 1, 3 and 6 h after ischemia significantly increased neuronal survival and behavioral performance and abolished the ischemia-evoked brain temperature increase. NBO treatment was most effective when applied 1 h after ischemia; later application had a weak or no protective effect. The results show that HBO and HBA applied between 1 and 6 h after ischemia prevent ischemia-evoked neuronal damage, which may be due to the inhibition of brain temperature increase, as a result of the applied rise in ambient pressure, and just not due to the oxygen per se. This perspective is supported by the finding that NBO treatment was less effective than HBO or HBA therapy. The results presented in this paper may pave the way for future experimental studies dealing with pressure and temperature regulation.
    Experimental Brain Research 01/2013; 224(1):1-14. DOI:10.1007/s00221-012-3283-5 · 2.04 Impact Factor
    • "Rats randomized to HBOT had reduced infarct size and improved neurological outcomes compared with untreated rats, and the degree of neurologic damage was highly correlated with the level of MPO activity.[30] In a separate model of cardiac arrest and resuscitation, the same investigators found that dogs treated with HBOT had better neurological outcomes and, histologically, fewer dying neurons than dogs treated conventionally.[31] The magnitude of neuronal injury correlated well with the neurological outcomes, but was not related to cerebral oxygen delivery or to the rate of oxygen metabolism. "
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    ABSTRACT: A brain injury results in a temporary or permanent impairment of cognitive, emotional, and/or physical function. Predicting the outcome of pediatric brain injury is difficult. Prognostic instruments are not precise enough to reliably predict individual patient's mortality and long-term functional status. The purpose of this article is to provide a guide to the strengths and limitations of the use of hyperbaric oxygen therapy (HBOT) in treating pediatric patients with severe brain injury. We studied total 56 patients of head injury. Out of them 28 received HBOT. Only cases with severe head injury [Glasgow Coma Scale (GCS) < 8] with no other associated injury were included in the study group. After an initial period of resuscitation and conservative management (10-12 days), all were subjected to three sessions of HBOT at 1-week interval. This study group was compared with a control group of similar severity of head injury (GCS < 8). The study and control groups were compared in terms of duration of hospitalization, GCS, disability reduction,and social behavior. Patients who received HBOT were significantly better than the control group on all the parameters with decreased hospital stay, better GCS, and drastic reduction in disability. In children with traumatic brain injury, the addition of HBOT significantly improved outcome and quality of life and reduced the risk of complications.
    Journal of Pediatric Neurosciences 03/2012; 7(1):4-8. DOI:10.4103/1817-1745.97610
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    • "Concerning the underlying molecular mechanisms, HBO was shown (iv) to attenuate the glucose utilization in the ischemic core (Lou et al., 2007), (v) to preserve the mitochondrial transmembrane potential and (vi) to decrease pro-apoptotic caspases after focal brain injury (Palzur et al., 2008). Consequently, reduced apoptosis or neuronal death were demonstrated as a result of HBO in transient global cerebral ischemia in gerbils (Konda et al., 1996), transient (Yin et al., 2003) and permanent focal cerebral ischemia in rat (Calvert et al., 2003), as well as canine cardiac arrest (Rosenthal et al., 2003). In a first report on simultaneously applied tPA and HBO following experimental embolic stroke in rats (Michalski et al., 2009), our group has noted inconsistent long-term effects with a tendency of increased neurological deficits after tPA +HBO, but improved functional recovery after tPA and tPA +HBO. "
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    ABSTRACT: Acute focal cerebral ischemia and consecutive energy failure are accompanied by neuronal death in regions with impaired cerebral blood flow. Several translational attempts of potential neuroprotective agents have failed, hence extended perspectives are required regarding the regional differences of neuronal impairment and glial involvement by using clinically relevant stroke models. This study aimed on neuronal loss following experimental focal cerebral ischemia, considering tissue plasminogen activator (tPA) as established treatment in stroke and hyperbaric oxygenation (HBO) as potential neuroprotective co-treatment. Wistar rats were subjected to embolic middle cerebral artery occlusion and underwent either treatment with tPA only, combined tPA+HBO, or no treatment. Neuronal impairment was assessed by Neuronal Nuclei (NeuN) staining in 4 ischemia-related areas and at 4 different time points after stroke induction (24hours, 7, 14 and 28 days). Additionally, spatial relationships between neuronal loss and gliosis were revealed by triple fluorescence staining of neurons, astrocytes and microglia, comparing the ipsi- and contra-lesional hemisphere. Analyzing the ischemic injury in general, a shell-like distribution of neuronal damage was observed, starting in the ischemic core and diminishing over the general ischemic area to the ischemic border zone and the primary non-affected area. This pattern remained detectable up to 4weeks after ischemia induction. Surprisingly, tPA and tPA+HBO did not markedly affect the post-ischemic course of neuronal impairment. Further studies are needed to investigate the effects of treatment with tPA or potential neuroprotective agents on neuronal integrity, with emphasis on the separation of intact neurons from those undergoing apoptosis or necrosis.
    Brain research 08/2011; 1417:115-26. DOI:10.1016/j.brainres.2011.08.024 · 2.84 Impact Factor
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