Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2.

Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month old male Sprague-Dawley rats and EAAT type 3 (EAAT3) knockout mice received or did not receive 30-min electroacupuncture once a day for five consecutive days. They were subjected to a 120-min middle cerebral arterial occlusion (MCAO) at 24h after the last electroacupuncture. Neurological outcome was assessed 2days after the MCAO. Brain tissues were harvested at 24h after the last electroacupuncture for Western blotting. Rats subjected to electroacupuncture at the Baihui acupoint had smaller brain infarct volumes and better neurological deficit scores than control rats. Electroacupuncture increased EAAT type 2 (EAAT2) in the cerebral cortex, tended to increase EAAT3 in the hippocampus, and had no effect on EAAT type 1 expression. Dihydrokainate, an EAAT2 inhibitor, worsened the neurological outcome of rats with electroacupuncture pretreatment. Electroacupuncture pretreatment at the Baihui acupoint increased EAAT2 in the cerebral cortex and improved the neurological outcome of EAAT3 knockout mice. Together, our results suggest that EAAT2 may mediate the electroacupuncture preconditioning-induced neuroprotection.

Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

BACKGROUND: Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. RESULTS: EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. CONCLUSIONS: EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats.

BACKGROUND: We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA. METHODS: Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD). RESULTS: Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release. CONCLUSION: These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.

Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral protection in patients undergoing coronary artery bypass graft surgery: a prospective, randomized, controlled clinical trial.

OBJECTIVES: To evaluate the cerebral and myocardial protective effects of hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery bypass graft surgery. DESIGN: A prospective, randomized, single-blinded study including patients scheduled for elective on-pump or off-pump surgery between December 2007 and February 2009. SETTING: A tertiary care university teaching hospital. PARTICIPANTS: Forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients. INTERVENTIONS: Patients were randomized to either the control (15 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) groups. Patients in the HBO groups underwent preconditioning for 5 days before surgery. MEASUREMENTS AND MAIN RESULTS: On-pump coronary artery bypass graft surgery patients preconditioned with HBO had significant decreases in S100B protein, neuron-specific enolase, and troponin I perioperative serum levels compared with the on-pump control group. Postsurgically, patients in the on-pump HBO group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs. Serum catalase activity 24 hours postoperatively was significantly increased compared with the on-pump control group. In the off-pump groups, there was no difference in any of the same parameters. CONCLUSIONS: Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing on-pump coronary artery bypass graft surgery. No protective effects were noted in off-pump coronary artery bypass graft surgery.

Cannabinoid receptor type 2 activation yields delayed tolerance to focal cerebral ischemia.

We demonstrated in our previous research that pretreatment with electroacupuncture (EA) induces rapid (2h after EA) and delayed (24h after EA) tolerance to focal cerebral ischemia. We further elucidate the endocannabinoid and cannabinoid receptor type 1(CB1) involvment in the rapid ischemic tolerance induced by EA pretreatment. The present study aimed at investigating the involvement of the cannabinoid receptor type 2 (CB2) in the neuroprotection conferred by EA pretreatment. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min at 2h and 24h following EA pretreatment in male Sprague-Dawley rats, respectively. Cerebral ischemic injury was evaluated by neurobehavioral scores and infarction volume percentages 72 h after reperfusion in the presence or absence of AM251, a selective CB1 receptor antagonist, and AM630, a selective CB2 receptor antagonist. The expression of CB1 and CB2 receptor in the striatum of ischemic hemisphere was also evaluated. The rapid and delayed ischemic tolerance induced by EA pretreatment was respectively reversed by AM251 and AM630. CB2 receptor expression was up-regulated in the striatum of rat brains at 24h after EA stimuli. These results indicate that CB2 receptor contributed to the delayed neuroprotective effect whereas CB1 receptor to the rapid ischemic tolerance induced by EA pretreatment against focal cerebral ischemia in rats.

Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1.

BACKGROUND AND PURPOSE: Our previous study has demonstrated that the rapid tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was possibly mediated through an endocannabinoid system-related mechanism. The purpose of this study was to investigate whether activation of epsilon protein kinase C (εPKC) was involved in EA pretreatment-induced neuroprotection via cannabinoid receptor type 1 in a rat model of transient focal cerebral ischemia. METHODS: The activation of εPKC in the ipsilateral brain tissues after EA pretreatment was investigated in the presence or absence of cannabinoid receptor antagonists. At 2 hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in rats. The neurobehavioral scores, infarction volumes, neuronal apoptosis, and the expression of Bcl-2 and Bax were evaluated after reperfusion in the presence or absence of εPKC-selective peptide inhibitor (TAT-εV1-2) or activator (TAT-ψεRACK). RESULTS: EA pretreatment enhanced εPKC activation. Systemic delivery of TAT-ψεRACK conferred neuroprotection against a subsequent cerebral ischemic event when delivered 2 hours before ischemia. Pretreatment with EA reduced infarct volumes, improved neurological outcome, inhibited neuronal apoptosis, and increased the Bcl-2-to-Bax ratio after reperfusion, and the beneficial effects were attenuated by TAT-εV1-2. In addition, the blockade of cannabinoid receptor type 1, but not cannabinoid receptor type 2 receptor, reversed the increase in εPKC activation and neuroprotection induced by EA pretreatment. CONCLUSIONS: EA pretreatment may activate endogenous εPKC-mediated anti-apoptosis to protect against ischemic damage after focal cerebral ischemia via cannabinoid receptor type 1, which represents a new mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia in rats.

Involvement of ERK 1/2 activation in electroacupuncture pretreatment via cannabinoid CB1 receptor in rats.

Our previous study demonstrated that pretreatment with electroacupuncture (EA) elicited protective effects against transient cerebral ischemia through cannabinoid receptor type 1 receptor (CB1R). In the present study, we investigated whether or not the extracellular signal regulated-kinase 1/2 (ERK1/2) pathway was involved in the ischemic tolerance induced by EA pretreatment through CB1R. At 24h after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120min in rats. The neurological scores and infarct volumes were evaluated at 24h after reperfusion. The expression of p-ERK1/2 in the brains was also investigated in the presence or absence of CB1R antagonist AM251. EA pretreatment reduced infarct volumes and improved neurological outcome at 24h after reperfusion, and the beneficial effects were abolished by U0126. The blockade of CB1R by AM251 reversed the up-regulation of p-ERK1/2 expression induced by EA pretreatment. Our findings suggest that the ERK1/2 pathway might be involved in EA pretreatment-induced cerebral ischemic tolerance via cannabinoid CB1 receptor in rats.

Cardioprotective effects of electroacupuncture pretreatment on patients undergoing heart valve replacement surgery: a randomized controlled trial.

BACKGROUND: Cardiac ischemia-reperfusion injury after cardiopulmonary bypass contributes to postoperative morbidity and mortality in patients with open-heart surgery. This randomized controlled trial was designed to address the protective effects of electroacupuncture (EA) pretreatment on myocardial injury in patients undergoing heart valve replacement surgery. METHODS: Sixty patients with acquired heart valve disease were randomly allocated to the EA pretreatment group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC 6), Lieque (LU 7), and Yunmen (LU 2) for 30 minutes each day for five consecutive days before surgery. Hemodynamic data, mechanical ventilation time, inotropic drug use in the intensive care unit, serum cardiac troponin I concentrations, morbidities, and mortalities were compared between the two groups. This trial is registered with ClinicalTrials.gov, number NCT00732459. RESULTS: At 6 hours, 12 hours, and 24 hours after reperfusion, levels of serum cardiac troponin I were significantly decreased in the EA group (5.74 +/- 0.67, 6.22 +/- 0.66, and 5.21 +/- 0.58) compared with that in the control group (7.89 +/- 0.74, 8.34 +/- 1.08, and 7.57 +/- 0.89, p < 0.05). The EA pretreatment significantly reduced overall serum troponin I release at 6 hours, 12 hours, and 24 hours after aortic cross-clamp removal. Meanwhile, EA pretreatment also reduced the inotrope score at 12 hours, 24 hours, and 48 hours after the intensive care unit arrival and shortened intensive care unit stay time (p < 0.05). CONCLUSIONS: The present study demonstrated that EA pretreatment may alleviate cardiac ischemia-reperfusion injury in adult patients undergoing heart valve replacements. This simple and convenient treatment has the potential to be used in the clinic for reducing myocardial injury in patients with heart valve replacement surgery.

Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.

BACKGROUND AND PURPOSE: Our previous study demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. The present study was aimed to investigate the involvement of the endocannabinoid system in the early neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia. METHODS: Two hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in male Sprague-Dawley rats or male C57BL/6 mice. The neurobehavioral scores, infarction volumes, and neuronal apoptosis were evaluated at 24 hours or 7 days after reperfusion in the presence or absence of AM251 (a selective cannabinoid receptor type 1 [CB1] receptor antagonist) or CB1 short interfering RNA. The expression of CB1 receptor and the content of endocannabinoids in the brains were also investigated. RESULTS: EA pretreatment reduced infarct size, improved neurological outcome, and inhibited neuronal apoptosis at 24 hours or 7 days after reperfusion. The beneficial effects were abolished by AM251. CB1 knockdown by CB1 short interfering RNA attenuated EA pretreatment-induced neuroprotection. EA pretreatment upregulated the neuronal expression of CB1 receptor in the rat brains and elevated the brain tissue content of the endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide. Pretreatment with 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide also reduced infarct size and improved neurological outcome. CONCLUSIONS: We conclude that pretreatment with EA increases the production of endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide, which elicits protective effects against transient cerebral ischemia through CB1 receptors. These results suggest a novel mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia.

Hyperbaric oxygen preconditioning induces tolerance against spinal cord ischemia by upregulation of antioxidant enzymes in rabbits.

The present study examined the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen (HBO) preconditioning is triggered by an initial oxidative stress and is associated with an increase of antioxidant enzyme activities as one effector of the neuroprotection. New Zealand White rabbits were subjected to HBO preconditioning, hyperbaric air (HBA) preconditioning, or sham pretreatment once daily for five consecutive days before spinal cord ischemia. Activities of catalase (CAT) and superoxide dismutase were increased in spinal cord tissue in the HBO group 24 h after the last pretreatment and reached a higher level after spinal cord ischemia for 20 mins followed by reperfusion for 24 or 48 h, in comparison with those in control and HBA groups. The spinal cord ischemic tolerance induced by HBO preconditioning was attenuated when a CAT inhibitor, 3-amino-1,2,4-triazole,1 g/kg, was administered intraperitoneally 1 h before ischemia. In addition, administration of a free radical scavenger, dimethylthiourea, 500 mg/kg, intravenous, 1 h before each day's preconditioning, reversed the increase of the activities of both enzymes in spinal cord tissue. The results indicate that an initial oxidative stress, as a trigger to upregulate the antioxidant enzyme activities, plays an important role in the formation of the tolerance against spinal cord ischemia by HBO preconditioning.

Rapid tolerance to focal cerebral ischemia in rats is induced by preconditioning with electroacupuncture: window of protection and the role of adenosine.

The aim of the present study was to investigate the first protective window of preconditioning with electroacupuncture (EA) against focal cerebral ischemia, and to explore whether adenosine is involved in the rapid tolerance phenomenon. Sixty-four male Sprague-Dawley rats were randomly assigned to eight groups (n=8 in each). Animals in the control group received no treatment, and animals in EA1-EA4 groups received EA at 0.5, 1, 2 and 3 h before induction of focal cerebral ischemia, respectively. Rats in DPCPX group were intraperitoneally injected with 1 mg kg-1 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 3 h before induction of focal cerebral ischemia. Animals in vehicle group and EA+DPCPX group were pretreated with 1 ml kg-1 dimethyl sulfoxide (DMSO, the solvent of DPCPX) and 1 mg kg-1 DPCPX 30 min before preconditioning with EA, respectively. All rats were anesthetized with 40 mg kg-1 pentobarbital sodium intraperitoneally. Animals that required EA preconditioning, received EA with intensity of 1 mA and frequency of 15 Hz at the Baihui acupoint (GV 20) for 30 min. The focal cerebral ischemia was produced by the right middle cerebral artery occlusion (MCAO) for 120 min. The neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h after reperfusion. All rats survived until 24 h after reperfusion. Preconditioning with EA at 2 h before induction of focal cerebral ischemia improved neurologic outcome (P<0.05 versus control) and reduced the infarct volume (P<0.01 versus control) at 24 h after reperfusion. These beneficial effects were reversed by pretreatment with 1 mg kg-1 DPCPX, whereas this agent itself did not affect the NDS and volume in drug-ischemic controls after ischemia. The results show that preconditioning with single EA session induces rapid tolerance to focal cerebral ischemia. The rapid ischemic tolerance appears at 2 h (but not at 0.5, 1, or 3 h) after preconditioning, and is possibly mediated through an adenosine A1 receptor-related mechanism.

[Experimental study of evaluation on neuroprotective effect for tetramethylpyrazine against focal cerebral ischemic injury with diffusion-weighted magnetic resonance imaging].

OBJECTIVE: To evaluate the neuroprotective effect of tetramethylpyrazine (TMP) against focal cerebral ischemic injury in rats with diffusion-weighted magnetic resonance imaging (DWMRI). METHODS: Rat models of focal cerebral ischemic injury were established in 16 male SD rats. They were randomly divided into the TMP group and the control group, eight in each group, and pretreated with TMP and normal saline respectively before modeling. Change of infarcted cerebral focus was observed with DWMRI at 1, 2, 6, 12 and 24 hrs after infarction, and the infarction volume (IV) at 24 hrs after modeling was estimated by triphenyltetrazolium chloride (TTC) stain. RESULTS: The IV in all time points observed in the TMP group with DWMRI was significantly smaller than that in the control group (P<0.01). Compared with that at 1 hr after infarction, in the control group at 2, 6, 12 and 24 hrs after modeling, the IV enlarged by 13.3%, 29.7%, 50.3% and 57.3% respectively, while that in the TMP group 9.9%, 21.3%, 37.1% and 40.5% respectively. The cerebral IV estimated by TTC stain 24 hrs after modeling was larger than that estimated by DWMRI. CONCLUSION: TMP pretreatment before modeling was effective in protecting brain against cerebral ischemic damage in rats. DWMRI dynamic scanning observation has important significance in observing the cerebral ischemic developing process and evaluating the effectiveness of brain protective measures.

Shenfu injection reduces toxicity of bupivacaine in rats.

OBJECTIVE: To investigate the effects of injecting Shenfu, an extract of traditional Chinese herbal medicines, on the central nervous system (CNS) and the cardiac toxicity of bupivacaine in rats. METHODS: Sixteen male Sprague-Dawley rats, weighing form 280 to 320 g, were randomly assigned to two groups (n = 8 in each group). Animals in the control group received a saline injection 10 ml/kg while animals in the Shenfu group received an injection of Shenfu 10 ml/kg intraperitoneally 30 minutes before intravenous infusion of bupivacaine. Lead II of an electrocardiogram (EEG) was continuously monitored after 3 needles were inserted into the skin of both forelimbs and the left hind-leg of each rat. The femoral artery was cannulated for measurement of arterial blood pressure and blood sampling. The femoral vein was cannulated for the infusion of bupivacaine. After baseline measurement (arterial blood pressure, heart rate and arterial blood gas), 0.5% bupivacaine was infused intravenously at a rate of 2 mg.kg(-1).min(-1) to all animals until asystole occurred. The time of bupivacaine-induced convulsions, arrhythmia and asystole were determined. The dose of bupivacaine was then calculated at the corresponding time point. RESULTS: The doses of bupivacaine that induced convulsions, arrhythmia and cardiac arrest were remarkably larger in Shenfu injection-treated animals than in saline-treated rats [convulsions, (10.5 +/- 1.9) mg/kg vs (7.2 +/- 1.5) mg/kg; arrhythmia (10.5 +/- 2.0) mg/kg vs (7.2 +/- 1.9) mg/kg; asystole, (32.8 +/- 8.5) mg/kg vs (25.0 +/- 5.0) mg/kg; P = 0.006, 0.009 and 0.044, respectively]. CONCLUSION: The Shenfu injection is able to reduce the toxicity of bupivacaine to CNS and cardiac system in rats.

Pretreatment with repeated electroacupuncture attenuates transient focal cerebral ischemic injury in rats.

OBJECTIVE: To investigate whether pretreatment with repeated electroacupuncture (EA) at the Baihui acupoint could induce ischemic tolerance against transient focal cerebral ischemic injury in rats. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=10 for each): the control group consisted of animals receiving no treatment, the isoflurane (ISO) group had animals that inhaled 1.5% isoflurane for 30 min a day for 5 days, and animals in the EA group received electroacupuncture at the Baihui acupoint for 30 min a day for 5 days under 1.5% isoflurane anesthesia. Twenty-four hours after the last treatment, the middle cerebral artery was occluded with No. 3 nylon monofilament for 120 min. The neurological outcomes were evaluated 24 h after reperfusion. The infarct volumes were then assessed using 2% triphenyltetrazolium chloride staining after the neurological outcome evaluation. RESULTS: The neurological deficit score (NDS) of the EA group [1 (0-2)] was lower than that of the ISO group [2 (1-3)] and the control group [2 (1-4)], P < 0.05. The infarct volume of the EA group (38.3 +/- 25.4 mm(3)) was significantly smaller than that of the control group (220.5 +/- 66.0 mm(3)) and the ISO group (168.6 +/- 57.6 mm(3)) 24 h after reperfusion. CONCLUSION: Electroacupuncture at the Baihui acupoint 30 min a day for 5 days significantly reduces neurological injury induced by transient middle cerebral artery occlusion.

[Effect of sodium ferulate on activation of extracellular signal regulated kinase after cerebral ischemia/reperfusion injury in rats].

OBJECTIVE: To study the activation of extracellular signal regulated kinase (ERK) after focal cerebral ischemia/reperfusion in rats and the effect of sodium ferulate (SF) on it. METHODS: Forty-five male adult SD rats were randomly divided into 3 groups, the sham-operated group, the control group and the SF group. The model of middle cerebral artery occlusion (MCAO) was established by thread ligation method, and in the ischemic phase, to rats in the sham-operated and the control group 4 ml of normal saline was intraperitoneally injected, and to rats in the SF group, 100 mg/kg of SF dissolved in 4 ml of normal saline was injected. The rats were decapitated at 2 hrs, 6 hrs, 12 hrs, 24 hrs and 72 hrs after reperfusion, 3 rats of every group at each time point, and rats brains were taken for immunohistochemistry and histopathological examination. RESULTS: Histopathological examination showed that the cerebral ischemic damage in the SF group was significantly milder than that in the control group at 2 hrs after reperfusion. The cerebral ischemia induced ERK activation reached the peak at 6 hrs and maintained to 72 hrs after reperfusion. As compared with the control group, the ERK activation in the SF group was significantly enhanced with increased positive immune reacted cells (P < 0.01). CONCLUSION: Cerebral ischemia/reperfusion could induce the activation of ERK in the ischemic brain cells, intervention of SF could enhance the activation and alleviate the ischemic injury in cerebral cortex.

Preconditioning with hyperbaric oxygen and hyperoxia induces tolerance against spinal cord ischemia in rabbits.

BACKGROUND: The aim of this study was to determine if the ischemic tolerance could be induced in the spinal cord by pretreatment with hyperbaric oxygen (HBO) and what components of HBO (hyperoxia, hyperbaricity, and combination of these two) were critical in the induction of tolerance against ischemic injury. METHODS: In experiment 1, 21 rabbits were randomly assigned to one of three groups (n = 7 each): animals in the control group received no HBO before spinal cord ischemia; animals in the HBO-1 and HBO-2 groups received HBO (2.5 atmosphere absolute [ATA], 100% O2) pretreatment 1 h/day for 3 and 5 days before ischemia, respectively. In experiment 2, 48 rabbits were randomly assigned to one of four groups (n = 12 each): the control group received no HBO (21% O2, 1 ATA, 1 h/day, 5 days) before spinal cord ischemia; the HB group received 1-h treatment in 21% O2 at 2.5 ATA each day for 5 days; the HO group received 1-h treatment in 100% oxygen at 1 ATA each day for 5 days; and the HBO group received HBO (2.5 ATA, 100% O2) treatment 1 h/day for 5 days. Twenty-four hours after the last treatment, spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, hind-limb motor function and histopathology of the spinal cord were examined in a blinded fashion. RESULTS: In experiment 1, the neurologic outcome in the HBO-2 group was better than that of the control group (P = 0.004). The number of normal neurons in the anterior spinal cord in the HBO-2 group was more than that of the control group (P = 0.021). In experiment 2, the neurologic and histopathologic outcomes in the HBO group were better than that of the control group (P < 0.01). The histopathologic outcome in the HO group was better than that in the control group (P < 0.05). CONCLUSIONS: Serial exposure to high oxygen tension induced ischemic tolerance in spinal cord of rabbits. Simple hyperbaricity (2.5 ATA, 21% O2) did not induce ischemic tolerance.