Correction to: Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

In the original publication of the article, the first sentence was published incorrectly under the section "Patients and preoperative assessment". The correct sentence should read as, "The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)".

Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

PURPOSE: We assessed the cerebrovascular CO2 reactivity (CO2R) in chronic renal failure (CRF) patients without diabetes mellitus (DM), uncontrolled hypertension, peripheral vascular disease, or neurological disease under isoflurane-nitrous oxide anesthesia. METHODS: Forty-nine patients undergoing surgery, including 36 CRF patients (30 receiving dialysis and six pre-dialysis patients) and 13 patients without CRF (controls). Middle cerebral artery flow velocity (VMCA) was measured by transcranial Doppler ultrasonography at an end-tidal CO2 of 35 to 45 mmHg. CO2R was calculated as an absolute value (change in VMCA per mmHg PaCO2) and a relative value (absolute CO2R/baseline VMCA × 100). Factors associated with CO2R were evaluated simultaneously. RESULTS: Despite no significant differences in the absolute and relative values of CO2R between the CRF (mean 2.5 cm/s/mmHg; median 5.0%/mmHg) and control (2.4 cm/s/mmHg; 5.0%/mmHg) groups, blood urea nitrogen (BUN) concentrations in the CRF group correlated inversely with both absolute and relative CO2R. BUN concentration was higher (mean 72 versus 53 mg/dl, p = 0.006) and relative CO2R was lower (mean 2.6 versus 5.7%/mmHg, p = 0.011) in patients with pre-dialysis CRF (n = 6) versus CRF patients receiving dialysis (n = 30). CONCLUSIONS: CO2R in CRF patients was not significantly different from that in controls. However, in CRF patients with high BUN concentrations, CO2R might be impaired, leading to reduced cerebrovascular reserve capacity. Because DM is a major cause of CRF and we excluded DM patients, our results might not be applicable to patients with DM-induced CRF.

Effects of a short-acting [beta]1 receptor antagonist landiolol on hemodynamics and tissue injury markers in patients with subarachnoid hemorrhage undergoing intracranial aneurysm surgery.

Sympathetic activation after subarachnoid hemorrhage (SAH) can induce tachycardia as well as cardiac and brain injury. We examined the effects of beta1 receptor antagonist landiolol on hemodynamics and the levels of tissue injury markers in patients with SAH. Fifty-six SAH patients undergoing intracranial aneurysm surgery with tachycardia (>or=90 beats per minute) randomly allocated to landiolol (L) or control (C) group were examined. In L group, landiolol was continuously administered during anesthesia. In C group, landiolol was not administered except bolus dose used in cases that exhibited uncontrolled tachycardia. Hemodynamics, the incidence of electrocardiographic abnormality, and levels of B-type natriuretic peptide, troponin T, S-100beta, 8-Hydroxy-2'-deoxyguanosine, interleukin-6 (IL-6), and IL-1 receptor antagonist were compared. Heart rate values from time of intubation to the end of anesthesia were significantly lower in L group than in C group, whereas blood pressure was similar between the groups. Although the incidence of bradycardia (<60 beats per minute) was significantly higher in L group than in C group (57% vs. 18%, respectively), bradycardia could be recovered without any adverse effects. The serum S-100beta levels 24 hours after operation were significantly lower in L group than in C group, whereas there were no significant differences in the incidence of electrocardiographic abnormality and levels of B-type natriuretic peptide, troponin T, 8-Hydroxy-2'-deoxyguanosine, IL-6, and IL-1 receptor antagonist between groups. We conclude that landiolol can be effectively used in the treatment of tachycardia in SAH patients and significantly reduced the serum S-100beta levels 24 hours after the operation.

Temporal profiles of aquaporin 4 expression and astrocyte response in the process of brain damage in fat embolism model in rats.

PURPOSE: Fat embolism syndrome is a serious complication observed after trauma, orthopedic surgery, and cardiac surgery. We investigated brain damage in relationship to temporal profiles of water channel aquaporin 4 (AQP4) and astrocyte response to fat embolism in rats. METHODS: Triolein (2 microl) was injected into the right internal carotid artery in rats. Neurological outcome (score: range, 0-5 = no deficit-dead), brain water content, histopathology, and immunohistochemistry for AQP4 and glial fibrillary acidic protein (GFAP) were evaluated at 2 h (2 h group, n = 12), 24 h (24 h group, n = 12), and 72 h (72 h group, n = 12) after triolein injection. Saline was injected in the control (C) group (n = 12). RESULTS: Neurological deficit score (median score of 2) and brain water content (mean value, 86.2%) increased significantly at 2 h with no progressive increase over 72 h. Damaged tissues with shrunken and triangular-shaped neurons with vacuole degeneration in cytoplasm and halo formation were distributed mainly, but not exclusively, to the ipsilateral hemisphere and were associated with increase in infiltration of inflammatory cells during the time course. Increases in immunostaining for AQP4 and GFAP were observed in the peri-affected region but not in the core. Reactive astrocytes with hypertrophy and dendrite elongation were detected at 72 h in the peri-affected region. CONCLUSION: The results suggest that brain damage with edema is induced very rapidly after triolein injection in association with increase in AQP4 expression and GFAP in the peri-affected region.

Repeated preconditioning with hyperbaric oxygen induces neuroprotection against forebrain ischemia via suppression of p38 mitogen activated protein kinase.

We previously reported in rats that preconditioning with hyperbaric oxygen (HBO; 100% O(2) 3.5-atomsphere absolute (ATA), 1 h/day for 5 days) provided neuroprotection against transient (8 min) forebrain ischemia possibly through protein synthesis relevant to neurotrophin receptor and inflammatory-immune system. A recent report suggested that HBO-induced neuroprotection is relevant to brain derived neurotrophic factor and its downstream event involving suppression of p38 mitogen activated protein kinase (p38) activation. In the present study, we first performed a dose comparison (1, 2, and 3.5 ATA) of HBO-induced neuroprotection and then investigated pharmacological modification by 10 mg/kg anisomycin (a protein synthesis inhibitor and potent activator for p38) and 200 microg/kg SB203580 (a p38 inhibitor), which were given intraperitoneally 60 and 30 min before every 3.5 ATA-HBO treatment, respectively. Most prominent protective effect on hippocampal CA1 neurons was observed with 3.5 ATA-HBO (survived neurons: 69% [62-73%] vs. untreated: 3.9% [2-8%], 1 ATA: 8.8% [0-26%], 2 ATA-HBO: 46% [22-62%] (median [range]) (7 days after ischemia). Anisomycin abolished a neuroprotective effect (survived neuron: 1.2% [0-7%]). SB203580, when given between administration of anisomycin and HBO treatment, resumed a neuroprotective effect (survived neuron: 52% [37-62%]). The level of phosphorylated p38 at 10-min reperfusion was significantly decreased in 3.5 ATA-HBO group (32% [12-53%] of sham). Single pretreatment with 100 and 200 microg/kg of SB203580 exerted a similar neuroprotective effect (39% [25-51%] and 59% [50-72%]) to 2 and 3.5 ATA-HBO preconditioning, respectively. It is concluded that suppression of p38 phosphorylation plays a key role in HBO-induced neuroprotection and that pretreatment with a p38 inhibitor (SB203580) can provide similar neuroprotection.

[Hypertension and tachycardia during endoscopic radial artery harvesting in two patients undergoing coronary artery bypass grafting].

Hypertension and tachycardia occurred during endoscopic radial artery harvesting in two patients undergoing coronary artery bypass grafting. Despite anesthesia maintained with moderate doses of fentanyl and isoflurane, hypertension and tachycardia occurred 10-15 min after tourniquet application and graft harvesting procedure. Tourniquet pain or direct stimulation to radial nerve by CO2 insufflation might be the causes. Although endoscopic radial artery harvesting is reported excellent for cosmetics with low incidence of complications such as infection and hematoma, hemodynamic change can occur during harvesting. Careful evaluation and management of hemodynamic changes should be exercised during this procedure in the patient with unstable angina and low cardiac function.

[Anesthetic management for electroconvulsive therapy in the patients with a history of neuroleptic malignant syndrome].

We report three patients with a history of neuroleptic malignant syndrome for whom modified electroconvulsive therapy (m-ECT) was scheduled. Two patients suffered from schizophrenia, and one suffered from depression. Their symptoms, such as hyperthermia, consciousness disturbance, myotonus, tremor, sweating, and tachycardia, improved gradually with administration of dantrolene and fluid infusion. However, their psychotic state was exacerbated. Therefore, m-ECT was scheduled. When patients were restless at the hospital ward, they were sedated with propofol and transferred to the operating room. General anesthesia was induced with thiopental 2.5-5 mg x kg(-1). After loss of consciousness, vecuronium bromide 0.01 mg x kg(-1) followed by a dose of 0.1 mg x kg(-1) was administered and ventilation was assisted using a face mask and 100% oxygen. After the ECT stimulus, the patients were sedated with propofol until full recovery from muscle relaxation. Although anesthesia time (mean 38 min) was slightly longer (19 min) than in those anesthetized with thiopental and suxamethonium chloride, m-ECT was performed safely and effectively.

Does high-dose opioid anesthesia exacerbate ischemic spinal cord injury in rabbits?

PURPOSE: Intrathecal morphine given during a post-ischemic period has been reported to have the potential to exacerbate ischemic spinal cord injury. However, it remains unknown whether synthetic opioids administered systemically exacerbate ischemic injury. We sought to compare the damage of the spinal cord after transient spinal cord ischemia in rabbits anesthetized with three different regimens; isoflurane, fentanyl with isoflurane, and remifentanil with isoflurane. METHODS: We assigned rabbits to three groups (n = 9 in each); an isoflurane group (isoflurane 1 minimum alveolar concentration [MAC]), a fentanyl group (isoflurane 0.5 MAC + 100 microg x kg(-1) i.v. fentanyl given over 30 min before aortic occlusion), and a remifentanil group (isoflurane 0.5 MAC + 1 microg x kg(-1) x min(-1) i.v. remifentanil started 30 min before aortic occlusion and maintained until 1 h after reperfusion). Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Hindlimb motor function (score range: 4, normal to 0, paraplegia) was assessed daily for 7 days, and then the number of normal neurons in the anterior spinal cord was counted. RESULTS: Severe motor dysfunction (score < or = 1) was observed in seven, four, and five animals in the isoflurane, fentanyl, and remifentanil groups, respectively. There were no significant intergroup differences in neurological scores. There were no differences in the numbers of normal neurons among the three groups (22 +/- 22, 42 +/- 30, 33 +/- 28, respectively). CONCLUSION: Our results suggest that neither i.v. fentanyl nor i.v. remifentanil added to 0.5 MAC isoflurane exacerbated ischemic spinal cord injury in rabbits when compared to 1 MAC isoflurane.

Prediction of postoperative delirium after abdominal surgery in the elderly.

PURPOSE: Indications for the surgical treatment of elderly patients have been increasing. Postoperative central nervous system dysfunction, including delirium, is one of the most common complications in elderly surgical patients. The relationship between patient factors, including cerebral oxygen saturation, and the incidence of postoperative delirium was evaluated. METHODS: Twenty American Society of Anesthesiologists (ASA) physical status I-II patients, older than 65 years, scheduled for elective abdominal surgery were enrolled in the study. The patients' cognitive function was assessed, using the Hasegawa dementia score (HDS) and kana-hiroi test, on the day before surgery and then again 1 week after the surgery. Regional cerebral oxygen saturation (rSO2) was continuously monitored during the surgery, using near-infrared spectroscopy (INVOS 3100). General anesthesia was induced with 3 mg x kg(-1) thiopental and 5% sevoflurane. After tracheal intubation, the sevoflurane concentration was adjusted to maintain the bispectral index (BIS) value between 45 and 60. Postoperative delirium was diagnosed if DSM IV criteria were present and the patient scored 12 or more points on the Delirium Rating Scale. RESULTS: After surgery, 5 (25%) patients developed delirium. The age in the delirium (+) group (76 +/- 4 years) was significantly higher than that in delirium (-) group (68 +/- 3 years). Preoperative and postoperative HDS did not differ between the groups. The score on the preoperative kana-hiroi-test in the delirium (+) group (16 +/- 5) was significantly lower than that in the delirium (-) group (32 +/- 10). There were no significant differences between preoperative and postoperative kana-hiroi test scores in either group. Baseline rSO2 in the delirium (+) group (60 +/- 5%) was significantly lower than that in the delirium (-) group (66 +/- 7%). However, there were no significant differences between the groups in the rSO2 after the start of surgery. CONCLUSION: Patients' age, low preoperative kana-hiroi test score, and low preoperative rSO2 were important risk factors for postoperative delirium.

Neutrophil elastase inhibitor attenuates hippocampal neuronal damage after transient forebrain ischemia in rats.

Inflammatory responses have been known to contribute to the development of neuronal damage after brain ischemia in experimental animals. Also, neutrophil elastase activity in the plasma has been elevated in the patients with acute cerebral infarction. In order to clarify whether neutrophil elastase distributes into the brain parenchyma and exacerbates neuronal damage following ischemia, we examined the effects of specific neutrophil elastase inhibitor, ONO-5046, on hippocampal CA1 neuronal death in relation to neutrophil elastase activity in the plasma and its distribution in the brain and to caspase-3/7 activity. ONO-5046 (5 and 10 mg/kg) or saline (control group) was administrated after 8 min of forebrain ischemia in rats. Ratio of surviving neurons (median, [range]) in hippocampal CA1 seven days after ischemia was significantly higher in the ONO-5046 5 mg/kg (31% [12-57%]), and 10 mg/kg groups (69% [39-76%]) than in the control group (3.2% [0-10%]). Plasma neutrophil elastase activity in the ONO-5046 10 mg/kg group was significantly lower than in the control group (14 [11-25] vs. 41 [35-68] nmol/ml). Neutrophil elastase distributed in the extracellular space in the hippocampal CA1 neuronal layer in the control group, while, in the ONO-5046 10 mg/kg group, trace of neutrophil elastase was detected only in the endothelium. Caspase-3/7 activity was elevated after ischemia over 8 h in the control group, while, in the ONO-5046 10 mg/kg group, no elevation was observed. The results suggest that neutrophil elastase may contribute to neuronal death in hippocampal CA1 following forebrain ischemia and that neutrophil elastase inhibitor attenuates neuronal death.

Critical alkalosis following intraperitoneal irrigation with sodium bicarbonate in a patient with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease, presenting with large amounts of mucinous ascites, and treatment with intraperitoneal irrigation with mucolytic agents has been tried. We report a patient with PMP who underwent intraperitoneal irrigation with sodium bicarbonate and exhibited marked alkalosis. The patient was a 78-year-old woman who had mucinous ascites, and an appendiceal and an ovarian tumor. Bilateral salpingo-oophorectomy and appendectomy were performed, and she then underwent intraperitoneal irrigation with sodium bicarbonate (7%, 1000 ml). Shortly after the irrigation, blood gas analysis showed critical alkalosis (pH, 7.66; base excess [BE], 24 mEq x l(-1); HCO3 (-), 50 mEq x l(-1)) with electrolyte imbalance (Na+, 153 mEq x l(-1); K+, 2.8 mEq x l(-1); Ca2+, 0.98 mEq x l(-1), Cl(-1), 99 mEq x l(-1)). The alkalosis and electrolyte imbalance were ameliorated with the administration of potassium chloride and calcium chloride intravenously, and the patient was extubated after the 2-h surgical procedure. The patient was discharged home after 15 days without problems. Sodium bicarbonate may be an effective mucolytic agent for PMP. However, during irrigation with sodium bicarbonate, careful evaluation of the acid-base balance and serum electrolytes, and prompt treatment of alkalosis or electrolyte imbalance, should this occur, are of great importance.

[Anesthesia management for fetoscopic treatment of twin-to-twin transfusion syndrome].

BACKGROUND: The fetoscopic laser coagulation of the vascular anastomoses on the monochorianic placenta for twin-to-twin transfusion syndrome (TTTS) has recently been shown to be effective. There have been few reports on the anesthetic techniques used for the fetoscopic laser coagulation. We report cases in which midazolam and fentanyl were used for the anesthetic management of the fetoscopic laser coagulation. METHODS: Twenty-two healthy (ASA I, II) women in the second trimester of pregnancy, carrying twins and scheduled for the fetoscopic laser coagulation for TTTS, were included. Midazolam 1 mg and fentanyl 2 microg x kg(-1) were infused intravenously before insertion of urethral catheter. Thereafter, fentanyl was infused at a rate of 2 microg x kg x hr(-1) lidocaine (1%, 5 ml) was administered locally. RESULTS: The procedure was performed successfully in 21 of 22 cases with acceptable pain. In one case, general anesthesia was necessary because the pain was not controlled. Maternal respiratory rate and end-tidal CO2 remained stable during the procedure. No patient had the respiratory rate below 10 breaths x min(-1). CONCLUSIONS: Continuous fentanyl infusion with midazolam provided acceptable maternal analgesia and sedation during endscopic treatment of TTTS. Careful titration with simulation of fentanyl concentration and respiratory monitoring enable safe and effective anesthesia management.

[Present state of anesthetic management for awake craniotomy in Japan].

To avoid the neurological deficits after neurosurgical procedures, awake craniotomy applying intraoperative awake functional brain mapping has been employed. Anesthesia for awake craniotomy requires particular attention to airway management, control of seizures and measures for decreasing the anxiety of the patients. We investigated the current status of anesthetic management for awake craniotomy in Japan to establish a standard procedure for safe anesthesia. A questionnaire was sent to 80 universities with departments of anesthesia in Japan and 34 (43%) responded. In 19 institutes, awake craniotomies are being practiced. The first experience of awake craniotomy was in 1996 in Japan and since then most of the institutes have experienced only three or fewer cases. Airway management, control of nausea and vomiting, stable awakening during functional mapping and control of seizures were pointed out as problems during awake craniotomy. Based on the present results, our experience and the information from previous investigations, standard anesthetic management for awake craniotomy in our country will be documented.

[Case of electrocardiogram showing ST depression after nonionic contrast media (iopromide) administration].

A 77-year-old man with coronary artery stenosis underwent the left limb artery bypass grafting. When the contrast media was administered on intraoperative limb reperfusion after revascularization, electrocardiogram showed ST depression without skin symptoms and blood pressure decline. The change was not in the right coronary artery area (99% stenosis), but in the left coronary artery area (50% stenosis). The nonionic contrast media may elicit coronary artery vasoconstriction, although there are few side effects including anaphylactic in comparison with the ionic contrast media. In administration of the nonionic contrast media to the patient with coronary artery stenosis (50% or more), it is important to examine electrocardiogram, and is advisable to administer coronary artery dilating drug before-hand.

[Anesthetic management for a patient with Huntington disease].

A 41-year-old man (169 cm, 48 kg), having a 10 year history of Huntington disease, was presented for percutaneous endoscopic gastrostomy because of repeated aspiration episodes. He had suffered from choreiform movements, misswallowing and progressive mental deterioration. Midazolam 2 mg i.v. was given on transferring the patient to the operating room. On arriving, the patient was somnolent but responded to call. BIS index was 55. Anesthesia was induced with thiopental 120 mg i.v. and fentanyl 100 microg i.v. followed by vecuronium 4 mg i.v. After tracheal intubation, anesthesia was maintained with sevoflurane 1.5% in 33% oxygen. Bispectral index and train of four ratio were monitored throughout the anesthesia. BIS index and TOF ratios were proper for the drug dose used. At the end of the procedure, neuromuscular blockade was antagonized with neostigmine 2.0 mg and atropine 1.0 mg i.v. with no worsening of symptoms. The duration of anesthesia was 85 minutes. The patient woke up (BIS index 78) and spontaneous respiration returned and he was extubated. The postoperative course was uneventful. In this case, BIS index was abnormally low before induction of anesthesia as well as after anesthesia. Whether Huntington disease is responsible for the abnormally low bispectral index remains uncertain. But, anesthesiologists should be aware of this phenomenon to avoid an inappropriate adjustment of the anesthetic depth.

[Survey on patients' impression of and degree of satisfaction to epidural anesthesia].

BACKGROUND: [corrected] Epidural analgesia is one of the methods to relieve pain after the operation. In general, patient-controlled epidural analgesia (PCEA) is efficient in providing high patient's satisfaction. However, it is not clear whether the patients are really satisfied with this analgesic technique in our hospital. Therefore, we studied this issue in 70 patients who had received elective surgery and epidural analgesia postoperatively. METHODS: We used questionnaires to investigate patients' impression of and degree of satisfaction to, epidural analgesia. We interviewed patients before operation and, 1 and 7 days after operation. We also evaluated PCEA usage, analgesic usage and side effects of epidural analgesia during the postoperative period. RESULTS: Preoperatively 80% of the patients had an anticipation of adequate analgesia with epidural analgesia. Although 54% of the patients had anxiety/fear during the epidural puncture, postoperative analgesia met their expectation in 86% of the patients. PCEA was used only in limited number of patients. CONCLUSIONS: The limited use of PCEA may be caused by inadequate information given to the patients. Therefore, it is necessary to give more easily understandable information to the patients about this analgesic procedure for better patients' acceptance, comfort and satisfaction.

Tight glycemic control by insulin, started in the preischemic, but not postischemic, period, protects against ischemic spinal cord injury in rabbits.

BACKGROUND: It is not well established whether insulin protects against ischemic spinal cord injury. We examined the effects of a single dose of insulin that corrects mild hyperglycemia on the outcome after transient spinal cord ischemia in rabbits. METHODS: We assigned rabbits to four groups (n = 8 in each); untreated control (C) group, preischemic insulin (Pre-I) group, preischemic insulin with glucose (GI) group (glucose concentrations were maintained at levels similar to the C group by the administration of glucose), and postischemic insulin (Post-I) group. Insulin (0.5 IU/kg) was administered 30 min before ischemia in the Pre-I and GI groups, and just after reperfusion in the Post-I group. Spinal cord ischemia was produced by occluding the abdominal aorta for 13 min. Neurologic and histopathologic evaluations were performed 7 days after ischemia. RESULTS: The mean blood glucose concentration before ischemia in the Pre-I group (118 mg/dL) was significantly lower than in the other three groups (158-180 mg/dL) and those of 30 min after reperfusion in the Pre-I (92 mg/dL) and Post-I (100 mg/dL) groups were significantly lower than in the C (148 mg/dL) and GI (140 mg/dL) groups. The motor function score and number of normal neurons in the anterior lumbar spinal cord in the Pre-I group were significantly greater than in the other three groups. CONCLUSIONS: These results suggest that a relatively small dose of preischemic insulin protects against ischemic spinal cord injury, and that the protective effects result from tight glycemic control before ischemia.

[Brain and spinal cord preconditioning for the protection against ischemic injury].

Recent studies have suggested that the brain preconditioning could induce tolerance to ischemia in humans. It has been believed that newly synthesized proteins are required for the acquisition of delayed tolerance in the brain and spinal cord. However, the mechanism other than the synthesis of neuroprotective proteins may also play a pivotal role. Preconditioning may reprogram the response to ischemic injury as seen during hibernation. Preconditioning with hyperbaric oxygen, volatile anesthetics, and xenon seems to be the focus of the attention from the standpoint of the clinical setting. Strong neuroprotection by the preconditioning with isoflurane and xenon is reported in animal experiments and may change the traditional idea of neuroprotection by anesthetics. The discovery that erythropoietin exerts neuroprotective properties has opened new therapeutic avenues. Erythropoietin is induced in the brain by hypoxic preconditioning and by the pharmacological preconditioning. In addition, the intravenous administration of erythropoietin has been shown to be safe and beneficial for acute stroke in humans. Therefore, erythropoietin is now one of the most promising neuroprotective agents. The research in the brain and spinal cord preconditioning will contribute to the elucidation of the mechanism of ischemic injury and to the establishment of new therapies for neuroprotection.

The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen.

Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons 55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection.