Effect of acute hypoxic preconditioning on qEEG and functional recovery after cardiac arrest in rats

Acute hypoxic preconditioning (AHPC) can confer neuroprotection from global cerebral ischemia such as cardiac arrest. We hypothesize that acute neuroprotection by AHPC will be detected early by quantitative EEG (qEEG) entropy analysis after asphyxial cardiac arrest (aCA). Cerebral ischemia lowers EEG signal randomness leading to low entropy. A qEEG entropy index defined as the duration when the entropy measure is 15% below uninjured baseline entropy is used as a measure of injury. We compared 3 groups of adult Wistar rats: (1) untreated controls that were subjected to 5 min of aCA and were resuscitated (n = 5); (2) AHPC-treated group with 10% FI O2 for 30 min, then 25 min of room air, 5 min of aCA followed by resuscitation (n = 5); and (3) a surgical sham group (no aCA) (n = 3). Functional outcome was assessed by neurodeficit score (NDS) which consisted of level of consciousness, cranial nerve, motor-sensory function, and simple behavioral tests (best = 100 and brain dead = 0). We found that increasing entropy index of injury at 0-5 h from return of spontaneous circulation (ROSC) is associated with worsening NDS at 24 h (linear regression: r = 0.81, P < 0.001). The NDS of the group sham (84.7 +/- 2.8) (mean +/- SEM) and AHPC group (84.6 +/- 2.9, P > 0.05) was better than control injury group (52.2 +/- 8.4, P < 0.05) (ANOVA with Tukey test). We therefore conclude that AHPC confers acute neuroprotection at 24 h, which was detected by qEEG entropy during the first 5 h after injury.     

Quantitative EEG and neurological recovery with therapeutic hypothermia after asphyxial cardiac arrest in rats

We test the hypothesis that quantitative electroencephalogram (qEEG) can be used to objectively assess functional electrophysiological recovery of brain after hypothermia in an asphyxial cardiac arrest rodent model. Twenty-eight rats were randomly subjected to 7-min (n = 14) and 9-min (n = 14) asphyxia times. One half of each group (n = 7) was randomly subjected to hypothermia (T = 33 degrees C for 12 h) and the other half (n = 7) to normothermia (T = 37 degrees C). Continuous physiologic monitoring of blood pressure, EEG, and core body temperature monitoring and intermittent arterial blood gas (ABG) analysis was undertaken. Neurological recovery after resuscitation was monitored using serial Neurological Deficit Score (NDS) calculation and qEEG analysis. Information Quantity (IQ), a previously validated measure of relative EEG entropy, was employed to monitor electrical recovery. The experiment demonstrated greater recovery of IQ in rats treated with hypothermia compared to normothermic controls in both injury groups (P < 0.05). The 72-h NDS of the hypothermia group was also significantly improved compared to the normothermia group (P < 0.05). IQ values measured at 4 h had a strong correlation with the primary neurological outcome measure, 72-h NDS score (Pearson correlation 0.746, 2-tailed significance <0.001). IQ is sensitive to the acceleration of neurological recovery as measured NDS after asphyxial cardiac arrest known to occur with induced hypothermia. These results demonstrate the potential utility of qEEG-IQ to track the response to neuroprotective hypothermia during the early phase of recovery from cardiac arrest.     

Removal of ECG interference from the EEG recordings in small animals using independent component analysis.

In experiments involving small animals, the electroencephalogram (EEG) recorded during severe injury and accompanying resuscitation exhibit the strong presence of electrocardiogram (ECG). For improved quantitative EEG (qEEG) analysis, it is therefore imperative to remove ECG interference from EEG. In this paper, we validate the use of independent component analysis (ICA) to effectively suppress the interference of ECG from EEG recordings during normal activity, asphyxia and recovery following asphyxia. Two channels of EEG from five rats were recorded continuously for 2 h. Simultaneous recording of one channel ECG was also made. Epochs of 4 s and 1 min were selected from baseline, asphyxia and recovery (every 10 min) and their independent components and power spectra were calculated. The improvement in normalized power spectrum of EEG obtained for all animals was 7.71+/-3.63 db at the 3rd minute of recovery and dropped to 1.15+/-0.60 db at 63rd minute. The application of ICA has been particularly useful when the power of EEG is low, such as that observed during early brain hypoxic-asphyxic injury. The method is also useful in situations where accurate indications of EEG signal power and frequency content are needed.     

Dexmedetomidine preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest

Background/Aims: To investigate the protection effect of dexmedetomidine preconditioning on global cerebral ischemic injury following asphyxial cardiac arrest (CA) in rats. Methods: Seventy-two rats were randomly assigned into three groups, sham group (no asphyxia), control group (asphyxia only), and dexmedetomidine preconditioned group (asphyxia + dexmedetomidine). Dexmedetomidine was administered 5 minutes before an 8 min of asphyxia. Rats were resuscitated by a standardized method. Blood O₂ and CO₂ partial pressures were, pH, base excess (BE), and blood glucose concentration measured before asphyxial CA and 1 h after resuscitation. Neurological deficit score (NDS) was measured at 12, 24, 48, and 72 h after CA. Histopathologic changes in the hippocampal region were observed by H&E staining and histopathologic damage score. Ultrastructural morphology was observed by transmission electron microscopy. HIF-1 and VEGF expression were measured by immunostaining of serial sections obtained from brain tissue. Results: Asphyxial CA -induced global cerebral ischemic decreased PaO₂, pH, BE and increased PaCO₂, blood glucose. Dexmedetomidine preconditioning improved neurologic outcome, which was associated with reduction in histopathologic injury measured by H&E staining, the histopathologic damage score and electron microscopy. Dexmedetomidine preconditioning also elevated HIF-1α and VEGF expression after global cerebral ischemia following asphyxial CA. Conclusion: Dexmedetomidine preconditioning protected against cerebral ischemic injury and was associated with upregulation of HIF-1α and VEGF expression.     

Quantitative EEG during early recovery from hypoxic-ischemic injury in immature piglets: burst occurrence and duration.

This study examined the course of EEG recovery in an animal model of hypoxic-ischemic injury. The model used periods of hypoxia, room air and asphyxia to induce cardiac arrest. One-week-old piglets (n = 16) were exposed to a period of hypoxia, room air and complete asphyxia for 7 minutes. After cardiac arrest and resuscitation, two EEG features were evaluated as prognostic indicators of behavioral outcome as assessed by a neuroscore at 24 hours after insult. A prominent EEG feature was the number and duration of bursts evident during recovery. Episodes of bursting were detected through the thresholds on sustained periods of elevated power. After the animal was resuscitated, the EEG was monitored continuously for 4 hours. To assess outcome in the recovering animal, a behavioral testing scale was used to test the animal's neurological capabilities. Trends of EEG burst counts were measured through thresholds on sustained power changes. Bursts are energy transients in the EEG record. High degrees of bursting were characteristic of animals having good neurological condition whereas piglets having low burst counts had poor 24 hr neuroscores. At 100 min the average burst rate of the good neuroscore outcome group was more than 8 per min and was significantly different from the poor outcome group's level of 2.7 (p < or = 0.05). When these counts were weighted by their total duration, differences between groups increased (p < or = 0.02). This study showed that the QEEG measure of burst counts and duration together provided a strong prognostic indication of the 24 hour outcome after asphyxic injury in a neonatal animal model. The critical determinant of the bursting character was the time when bursting occurred. Bursting occurring early in recovery was a good gauge of outcome. We conclude that quantitative EEG analysis and interpretation can be an important tool for the outcome determination during recovery from cerebral injury states.     

Early restitution of electrocorticogram predicts subsequent behavioral recovery from cardiac arrest.

Previous studies have shown that parameters of EEG restitution reflect the severity of global hypoxic-ischemic brain injury. Here, the hypothesis is tested that patterns of EEG restitution during the first 4 hours predict later behavioral recovery. Time course and correlations between behavior, electrocorticogram (EcoG), and neuronal injury were investigated in a rodent model of asphyctic cardiac arrest. Forty Wistar rats were subjected to 5 minutes of asphyxia and cardiopulmonary resuscitation. Behavior was assessed by repeated scoring of neurodeficits and open field activity until euthanasia at 48 hours. Electrocorticographic bursting occurred at 13.2 +/- 4 minutes after resuscitation. Bursts increased in frequency and duration until the EcoG reverted to a continuous signal. The resuscitation-continuous EcoG interval correlated with the first appearance of spontaneous movements (r = 0.80, P < 0.05). Larger intervals were associated with hyperactivity in the open field at 24 hours (r = 0.61, P < 0.05), indicating a more severe behavioral deficit. Larger intervals were also associated with worse 48-hour neurodeficit scores (P < 0.05). Neuronal damage in the hippocampus correlated with the degree of open field hyperactivity at 14 hours (P < 0.05). These findings demonstrate a close temporal and prognostic relationship between electrical and behavioral recovery after hypoxic-ischemic brain injury.     

The impact of repeated short episodes of circulatory arrest on cerebral function. Reassuring electroencephalographic (EEG) findings during defibrillation threshold testing at defibrillator implantation

The impact of circulatory arrest on EEG features during defibrillation threshold testing for implantation of a cardioverter defibrillator has been disputed. Cumulation of cerebral ischemic effects during threshold testing has been observed, and consequently the advice was given to avoid short intervals between tests and to limit the test number. This study investigated the duration of EEG signs of cerebral ischemia as well as the occurrence of cumulation. EEGs were recorded during standardized general anesthesia. Subsequent tests were performed after recovery of EEG, electrocardiogram, systemic arterial blood pressure, and heart rate.In 36 consecutive survivors of out-of-hospital cardiac arrest 286 episodes of induced circulatory arrest were analyzed. Ischemic EEG changes were present in all episodes of circulatory arrest, consisting of slowing, progressing to absence of activity. The relation between the onset time or recovery time and the test number and test interval was studied.A highly significant correlation between circulatory arrest and recovery time was found (P < 0.001). A significant negative correlation existed between test number and recovery time (P < 0.05). Test interval was not related with either onset or recovery time.We conclude that repeated threshold tests which are monitored by assessment of EEG and hemodynamics are not associated with cumulative EEG changes as a result of ischemia. Our results do not support the advice that the number of tests should be limited.     

双氧水预处理对大鼠局灶性脑缺血损伤及氧自由基的影响

目的探讨双氧水预处理对大鼠局灶性脑缺血损伤及氧自由基的影响。方法实验一：20只雄性sD大鼠，随机分为单纯缺血再灌注组和双氧水预处理组（每组10只）。实验二：18只雄性SD大鼠分为空白对照组，单纯缺血再灌注组和双氧化预处理（每组6只）。预处理组动物于缺血前24h用微量泵1h内静脉内缓慢泵入3％的双氧水1ml。动物再灌注后24h，对实验一两组动物行神经功能障碍评分，并处死动物取大脑行TFC染色测量脑梗死容积；取实验二的所有动物的脑组织行超氧化物歧化酶（SOD）和神经元特异性烯醇酶（NSE）测定。结果双氧化预处理组神经功能损害评分和脑梗死容积明显较对照组低（P〈0．05）。缺血再灌注组SOD含量和NSE含量明显低于对照组和双氧水预处理组（P〈0.05）。结论双氧水预处理可诱导超氧化物歧化酶生成，降低自由基对大脑的损害，对大鼠局灶性脑缺血损伤具有明显的保护作用。     

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.     

Reductions in qEEG slowing over 1 year and after treatment with Cerebrolysin in patients with moderate–severe traumatic brain injury

Changes in quantitative EEG (qEEG) recordings over a 1-year period and the effects of Cerebrolysin (Cere) on qEEG slowing and cognitive performance were investigated in postacute moderate-severe traumatic brain injury (TBI) patients. Time-related changes in qEEG activity frequency bands (increases of alpha and beta, and reductions of theta and delta relative power) and in qEEG slowing (reduction of EEG power ratio) were statistically significant in patients with a disease progress of less than 2 years at baseline, but not in those patients having a longer disease progress time. Slowing of qEEG activity was also found to be significantly reduced in TBI patients after 1 month of treatment with Cere and 3 months later. Therefore, Cere seems to accelerate the time-related reduction of qEEG slowing occurring in untreated patients. The decrease of qEEG slowing induced by Cere correlated with the improvement of attention and working memory. Results of this exploratory study suggest that Cere might improve the functional recovery after brain injury and encourage the conduction of further controlled clinical trials.     

急性脑梗死患者发生脑心综合征的相关因素

目的探讨急性脑梗死患者发生脑心综合征(CCS)的相关因素。方法比较86例CCS和90例非CCS急性脑梗死患者的血浆B型利钠肽(BNP)水平、心肌酶谱水平、EEG异常率、神经功能缺损程度评分(NDS)、左室射血分数(LVEF)和左室舒张内径(LVEDD),并进行相关性分析。结果 CCS组[(1482.93±233.76)pg/ml]血浆BNP水平显著高于非CCS组[(164.53±27.05)pg/ml](P<0.05),而心肌酶谱指标差异无统计学意义。与非CCS组比较,CCS组ECG异常率显著增高(P<0.05),而LVEDD、LVEF和NDS的差异均无统计学意义。血浆BNP水平与乳酸脱氢酶及NDS重型呈正相关(r=0.360,r=0.382;均P<0.05)。经多元Logistic回归分析显示,血浆BNP水平是CCS的独立影响因素(r=6.852,P=0.009)。根据ROC曲线,BNP诊断CCS的分界值取219.95 pg/ml时,曲线下面积为0.938(95%CI:0.865～1.010;P<0.01),敏感性为93.8%,特异性为80.0%。结论血浆BNP水平是CCS的独立影响因素之一。     

Kynurenate inhibition of cell excitation decreases stroke size and deficits

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad-spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4-hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p less than 0.001) and improved neurological outcome (p less than 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.     

缺血后处理对脑缺血再灌注损伤大鼠的脑保护作用及其最佳时间窗的探讨

目的探讨缺血后处理(IP)对大鼠局灶性脑缺血再灌注(I/R)神经保护作用的最佳时间窗。方法 80只雄性SD大鼠,随机分为5组(假手术组、对照组、IP 15s组、IP 30s组和IP 1min组)。假手术组和对照组行单纯I/R;IP 15s组、IP 30s组和IP 1min组,反复3次缺血再灌注。除假手术组外的大鼠均采用线栓法闭塞大鼠大脑中动脉(MACO)建立脑缺血SD大鼠模型。所有大鼠行神经功能障碍评分(NDS),并应用组织原位标记凋亡细胞检测、免疫组织化学等技术观察IP后海马CA1区细胞凋亡及肿瘤坏死因子(TNF-α)表达的变化。结果再灌注24 h后,IP各组NDS明显低于对照组(P<0.05),其中IP 15s组、IP 30s组NDS低于IP 1min组(P<0.05)。对照组海马CA1区TNF-α、凋亡细胞表达量明显增加,IP 15s组、IP 30s组海马CA1区TNF-α、凋亡细胞的表达量较IP 1min组明显下降(P<0.05)。结论 IP可改善局灶性脑缺血大鼠的神经功能、减少海马CA1区炎性因子TNF-α及细胞凋亡的表达。大鼠局灶性脑缺血再灌注损伤保护作用的最佳时间窗为15s、30s。     

Quantitative electroencephalography spectral analysis and topographic mapping in a rat model of middle cerebral artery occlusion

Electroencephalography (EEG) has a long history in clinical evaluations of cerebrovascular disease. Distinct EEG abnormalities, such as increased slow delta activity, voltage depression and epileptiform discharge, have been identified in stroke patients. However, preclinical use of EEG analysis of cerebral ischaemia is less documented. We report a new rat model of EEG topographic mapping during permanent and transient middle cerebral artery occlusion. Ten EEG electrodes were implanted on the rat skull, symmetrically covering the cortical regions of two hemispheres. Monopolar EEG recordings were acquired from each animal at multiple time points during the initial 24 h, and again once daily for 7 days. Traditional EEG examinations, quantitative EEG (qEEG) spectral analysis and topographic EEG mapping were employed for comprehensive data analyses. Several distinct spatiotemporal EEG abnormalities were identified in the ischaemic rat brain. In the ipsilateral hemisphere, pronounced increase in delta activity was observed in each recorded area within 24 h of injury. While sharp waves and spike complexes dominated the parietal region, a nearly isoelectric EEG state was seen in the temporal region. After 48 h, spontaneous, albeit incomplete, recovery of EEG activities developed in all rats. Reperfusion appeared to promote delta and alpha recovery more efficiently. The contralateral EEG changes were also recorded in two phases: an acute moderate increase in delta activities with intermittent rhythmic activities, followed by a delayed and significant increase in beta activities across the hemisphere. The similarities of rat qEEG profiles identified in this study to that of stroke patients and the application of topographic mapping broaden our research technology for preclinical experimental studies of brain injury.     

Stimulation of the fastigial nucleus enhances EEG recovery and reduces tissue damage after focal cerebral ischemia.

Stimulation of the cerebellar fastigial nucleus (FN) increases CBF but not metabolism and reduces the tissue damage resulting from focal cerebral ischemia. This effect may result from enhancing CBF in the ischemic tissue without increasing local metabolic demands. To test this hypothesis, we studied whether the reduction in tissue damage is restricted to the neocortex, a region in which the CBF increase is independent of metabolism, and whether stimulation of the dorsal medullary reticular formation (DMRF), a treatment that increases both cerebral metabolism and CBF, also protects the brain from ischemia. In halothane-anesthetized Sprague-Dawley rats, the middle cerebral artery (MCA) was occluded either proximally or distally to the lenticulostriate branches. The FN or DMRF were then stimulated for 1 h (50-100 microA; 50 Hz; 1 s on/l s off). Twenty-four hours later, the infarct volume was determined. FN stimulation substantially reduced the size of the infarct, an effect that was greater with distal (-69 +/- 8%; n = 6; p < 0.001; mean +/- SD) than with proximal (-38 +/- 8%; n = 8; p < 0.001) MCA occlusion. The reduction occurred only in neocortex (-43 +/- 9%; p < 0.001) and not in striatum (-16 +/- 21%; p > 0.05). Stimulation of the FN also enhanced recovery of EEG amplitude in the ischemic cortex (+48%; p < 0.003). DMRF stimulation (n = 7) did not affect the stroke size or EEG recovery (p > 0.05). Thus, stimulation of the FN, but not the DMRF, attenuates the damage resulting from focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurobehavioral consequences of induced spreading depression following photothrombotic middle cerebral artery occlusion

In a model of experimental focal cerebral ischemia, we have recently reported a strong correlation between the magnitude of ischemic depolarizations in the peri-infarct borderzone and the extent of histological injury. In the present study, we assessed the neurobehavioral consequences of spontaneously occurring and induced ischemic depolarizations in rats following middle cerebral artery (MCA) occlusion, as well as the effects of induced spreading depression (SD) in intact animals. Halothane-anesthetized, artificially ventilated Sprague-Dawley rats underwent photothrombotic MCA occlusion coupled with ipsilateral common carotid artery (CCA) occlusion. The electroencephalogram and direct current (DC) potential were recorded in the parietal infarct borderzone-corresponding to the cortical forelimb area-for 3 h following MCA occlusion. Group 1 rats (n = 9) received MCA/CCA occlusion, and the spontaneously occurring negative DC shifts were recorded in the ischemic borderzone. In Group 2 animals (n = 9), the (non-ischemic) frontal pole of the ipsilateral hemisphere was electrically stimulated in order to double the frequency of peri-infarct DC shifts occurring over the initial 3 h postocclusion. Group 3 consisted of intact rats (n = 3) in which SD was repeatedly evoked in the frontal pole. Four animals served as sham-operated controls. A battery of sensorimotor behavioral tests, consisting of beam balance, postural reflex and elicited forelimb placing, was applied in a blinded fashion. Sham controls and animals of Groups 1 and 2 were tested 24 h after surgery, and Group 3 rats were tested 2, 6 and 24 h after generation of SDs. A cumulative neurobehavioral index, ranging from 0 to 144, was calculated by adding the individual test results. Brains were perfusion-fixed 24 h following surgery for calculation of volumes of infarction and scattered neuronal injury. Functional outcome at 24 h was significantly worse in Group 2 animals (spontaneous plus induced ischemic depolarizations) (neurobehavior index 43 ± 19, mean ± S.D.) compared to Group 1 rats, in which only spontaneous depolarizations occurred (neurobehavior index 24 ± 19,P < 0.05). The cumulative neurobehavioral index of Group 1 and 2 animals correlated positively with the volume of total ischemic injury (r = 0.765, P < 0.001) and with the frequency of ischemic depolarizations (r = 0.474, P < 0.05). Correlations between severe forelimb placing deficits and severe degrees of histological injury (necrosis or ischemic cell change) in the corresponding primary sensorimotor cortical region FR1 were significant in these rats. Group 3 rats showed severe neurobehavioral deficits at 2 and 6 h following SD stimulation (index 57 ± 1 and 39 ± 1, respectively) but returned to normal at 24 h (4 ± 0). The findings indicate that cortical spreading depression is accompanied by transient neurobehavioral deterioration and that SD in the ischemic hemisphere of animals subjected to MCA occlusion worsened functional outcome 24 h after surgery.     

预防性应用阿托伐他汀对SD大鼠局部脑缺血再灌注脑组织Caspase-3表达的影响

目的 探讨预防性应用阿托伐他汀对SD大鼠局灶性脑缺血再灌注损伤是否具有脑保护作用及其可能的机制.方法 72只雄性SD大鼠,按随机化原理分成3组:假手术组(n=24)、缺血再灌注组(简称对照组n=24)、阿托伐他汀组(n=24),各组按缺血2 h再灌注2 h、6 h、24 h、36 h分为4个亚组,每组各6只.结果 各相同再灌注时间点,阿托伐他汀组与对照组比较,缺血区变性、坏死的神经元数量减少,空泡样改变减轻,组织间水肿减轻.阿托伐他汀组较对照组Caspase-3阳性表达细胞数明显减少,再灌注2 h、6 h,2组间比较差别有统计学意义(P＜0.05),再灌注24 h及36 h 2组间比较差别有显著性统计学意义(P＜0.01).结论 预防性应用阿托伐他汀能减轻SD大鼠局灶性脑缺血再灌注损伤,减轻神经细胞变性、坏死及组织水肿,使缺血周边区及海马区Caspase-3表达减少.     

Sevoflurane-induced preconditioning protects against cerebral ischemic neuronal damage in rats

In the present study, we tested the ability of sevoflurane to induce early and late preconditioning against ischemic neuronal injury using an in vivo model of global cerebral ischemia in the rat. Seven-minute global ischemia was induced by cardiac arrest, followed by resuscitation and recovery for 7 days. Hippocampal slices were then prepared and the amplitude of extracellularly recorded, orthodromically evoked, CA1 population spikes (neuronal function) was quantified. Rats were preconditioned for 30 min with 1.0 minimum alveolar concentration (MAC) of sevoflurane once or on 4 consecutive days, 15 min (single exposure, early) or 24 h (four exposures, late preconditoning) prior to cardiac arrest. After early or late preconditioning, sevoflurane reduced ischemic neuronal damage from 43 +/- 3% [sham rats, (mean +/- SEM)] to 30 +/- 3% and 35 +/- 4%, respectively. Histopathology demonstrated a preserved morphology of the CA1 region of preconditioned rats, whereas pyknosis was present in control and sham-treated rats. Sevoflurane-induced preconditioning confers neuroprotection during an early as well as late time window.     

Sleep homeostasis in suprachiasmatic nuclei-lesioned rats: effects of sleep deprivation and triazolam administration

The electroencephalogram (EEG) and electromyogram of rats with lesions in the suprachiasmatic nuclei (SCNx) were recorded during two series of 24-h baseline, 6-h sleep deprivation (SD), and 24-h recovery. At recovery onset, rats were injected i.p. with vehicle (VEH) control solution or 0.4 mg/kg triazolam (TRZ) in a balanced crossover design. Consecutive 10-s epochs were scored for vigilance states and EEG power spectra were computed. Arousal states were uniformly distributed during 24-h baseline (wake 47% of recording time, non-rapid-eye movement sleep (nonREMS) 47%, REMS 7%), and EEG spectra (0-25 Hz) were devoid of significant trends. State-specific EEG power spectra profiles in SCNx rats were similar to those of intact animals reported previously. However, EEG delta power (0.5-3.5 Hz) of nonREMS was markedly lower in SCNx rats. Recovery from 6-h SD was characterised by a short-lasting reduction of REMS, and a long-lasting increase of nonREMS time at the cost of wakefulness. EEG delta power rebounded during the first 8 h in recovery, and fell below baseline level after 12 h in recovery. During 0-2 h TRZ recovery, rats spent more time in nonREMS with higher EEG slow wave activity as compared to the corresponding VEH recovery period. EEG slow wave activity fell below baseline levels 10 h after TRZ injection and termination of SD. We conclude that major features of homeostatic sleep EEG regulation are present in SCNx rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

The development of spectral EEG changes during short periods of circulatory arrest.

The EEG was monitored in 56 patients during implantation of an internal cardioverter defibrillator. The purpose of this study was to determine the main EEG frequency ranges that represent ischemic changes during short periods of circulatory arrest. The EEG was recorded with a 16-channel common reference montage (Cz). After onset of circulatory arrest, the log spectral changes of three-epoch moving averages were calculated relative to the baseline spectrum. For factor analysis, 17 EEG periods were selected that showed changes progressing to an isoelectrical period. Topographic differences and the time course of quantitative EEG (qEEG) changes were studied in all 56 patients. For each patient the EEG period with the longest duration of circulatory arrest was chosen. Factor analysis revealed four factors that represented the spectral EEG changes occurring during circulatory arrest and recovery. The frequency intervals of these factors were 0 to 0.5 Hz, 1.5 to 3 Hz, 7.5 to 9.5 Hz, and 15 to 20 Hz for all channels. Only minor topographic differences were found in the power of the spectral changes; the sequence of events was similar for all electrode positions. The first EEG change after circulatory arrest was an initial increase in alpha power and a decrease in beta power. On average, after approximately 15 seconds alpha power started to decrease, beta power decreased further, delta-1 power started to increase, and delta-2 power started to decrease. After approximately 25 seconds, the delta-1 power increase appeared to plateau or to decrease. A circulatory arrest longer than approximately 30 seconds resulted in an isoelectrical EEG. After restoration of the circulation, there was a fast transient increase in delta-1 and delta-2 power, followed by a decrease to baseline. alpha and beta power showed a more gradual increase in power toward baseline and were the last to restore after 60 to 90 seconds. In general, the spectral changes in the alpha and beta frequency ranges were most pronounced and consistent. In conclusion, to detect intraoperative cerebral ischemia, monitoring of changes in the four frequency ranges found is preferable to monitoring changes in the classically defined frequency bands. Furthermore, these results stress the importance of the alpha and beta ranges in detecting cerebral ischemia.