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.     

Interleukin-1 receptor antagonist attenuates regional neuronal cell death and cognitive dysfunction after experimental brain injury.

The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region (P < 0.05), dentate hilus (P < 0.05), and cortex (P < 0.05) but impaired recovery of motor function at 7 days after trauma (P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours (P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.     

Factors predictive of seizures and neurologic outcome in perinatal depression

To identify which early clinical variables are predictive of outcome in newborns with perinatal depression, we prospectively examined newborns with persistently abnormal neurologic examinations at 48 hours and (1) arterial pH 相似文献   

MAPK信号转导通路中ERK、JNK和P38在大鼠肝脏缺血再灌注和缺血后处理中表达的变化

背景：近年来,随着器官移植的不断开展和深入研究,人们逐渐认识到供肝原发性无功能是引起肝移植患者早期死亡的主要原因,而缺血再灌注损伤是导致供肝功能不良的重要因素。如何减轻或消除缺血再灌注损伤一直是临床研究的热点。 目的：观察肝缺血再灌注损伤和缺血后处理后MAPK级联通路中P38,JNK和ERK活化的情况。 设计、时间及地点：随机对照动物实验,于2007-05/10在中南大学湘雅医院动物实验中心完成。 材料：102只Wistar大鼠随机分为假手术组6只,缺血30 min再灌注组48只和缺血后处理组48只,后2组又分为0,0.5,1,2,4,8,12,24 h不同时间处理亚组,每亚组6只。 方法：建立大鼠肝脏体内局部缺血再灌注-缺血后处理模型,于复灌后0,0.5,1,2,4,8,12,24 h取肝脏组织。 主要观察指标：应用免疫组织化学的方法对磷酸化的p-P38、p-JNK和p-ERK进行免疫组化检测并作半定量分析。 结果：①p-ERK,p-JNK在缺血后即有轻度增高,但在再灌注后30 min开始增高明显,持续到再灌注后4 h,高峰出现在再灌注后2 h。缺血后处理组p-ERK,p-JNK的表达在再灌注后1,2,4 h较缺血再灌注组增高(P < 0.05)。②p-P38在缺血后即有轻度地增高,但在再灌注后30 min开始增高明显,高峰出现在再灌注后1 h,2 h后开始下降,表达程度维持在缺血后水平。与缺血再灌注组相比,缺血后处理组p-P38的表达增高,但仅在再灌注后1 h明显增高(P < 0.05)。 结论：缺血后处理可通过增高ERK和P38的磷酸化水平,降低JNK的磷酸化水平减轻缺血再灌注导致的肝脏损伤。     

Outcome after ischemia in the developing sheep brain: an electroencephalographic and histological study.

The role of seizures occurring with perinatal hypoxic-ischemic encephalopathies is unclear. We examined the relationships between the time course of parasagittal electroencephalographic (EEG) activity and pathological outcome following transient cerebral ischemia, which was induced in 33 chronically instrumented fetal sheep by occluding the carotid arteries after ligation of the vertebral-carotid anastomoses. The EEG was quantified with real-time spectral analysis. Histological outcome was assessed 72 hours later. After 10 or 20 minutes of ischemia, EEG activity was depressed and then progressively recovered and mild selective neuronal loss was seen. The length of this depression correlated with the duration of ischemia (r = 0.88). After 30 or 40 minutes of ischemia, EEG activity remained depressed for 8 +/- 2 hours, followed by a rapid transition to low-frequency epileptiform activity that reached maximum intensity at 10 +/- 3 hours. By 72 hours, EEG intensity had fallen below control levels. This sequence of prolonged depression, epileptiform activity, and then loss of intensity was associated with the development of laminar necrosis of the underlying cortex. These electrophysiological sequelae may have prognostic value. The results indicate that after a severe hypoxic-ischemic insult, the parasagittal cortex becomes hyperexcitable before the final loss of activity. Secondary neuronal death may occur in this phase.     

MK-801 does not protect against hypoxic-ischemic brain injury in piglets

BACKGROUND AND PURPOSE: The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801. METHODS: Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group). RESULTS: Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups. CONCLUSIONS: MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.     

Cervical Vagus Nerve Stimulation Improves Neurologic Outcome After Cardiac Arrest in Mice by Attenuating Oxidative Stress and Excessive Autophagy

BackgroundCerebral ischemia and reperfusion (I/R) induces oxidative stress and activates autophagy, leading to brain injury and neurologic deficits. Cervical vagus nerve stimulation (VNS) increases cerebral blood flow (CBF). In this study, we investigate the effect of VNS-induced CBF increase on neurologic outcomes after cardiac arrest (CA).Materials and MethodsA total of 40 male C57Bl/6 mice were subjected to ten minutes of asphyxia CA and randomized to vagus nerve isolation (VNI) or VNS treatment group. Eight mice received sham surgery and VNI. Immediately after resuscitation, 20 minutes of electrical stimulation (1 mA, 1 ms, and 10 Hz) was started in the VNS group. Electrocardiogram, blood pressure, and CBF were monitored. Neurologic and histologic outcomes were evaluated at 72 hours. Oxidative stress and autophagy were assessed at 3 hours and 24 hours after CA.ResultsBaseline characteristics were not different among groups. VNS mice had better behavioral performance (ie, open field, rotarod, and neurologic score) and less neuronal death (p < 0.05, vs VNI) in the hippocampus. CBF was significantly increased in VNS-treated mice at 20 minutes after return of spontaneous circulation (ROSC) (p < 0.05). Furthermore, levels of 8-hydroxy-2?-deoxyguanosine in the blood and autophagy-related proteins (ie, LC-3Ⅱ/Ⅰ, Beclin-1, and p62) in the brain were significantly decreased in VNS mice. Aconitase activity was also reduced, and the p-mTOR/mTOR ratio was increased in VNS mice.ConclusionsOxidative stress induced by global brain I/R following CA/ROSC leads to early excessive autophagy and impaired autophagic flux. VNS promoted CBF recovery, ameliorating these changes. Neurologic and histologic outcomes were also improved.     

Window of opportunity of cerebral hypothermia for postischemic white matter injury in the near-term fetal sheep.

Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4 +/- 0.1 degrees C to between 30 and 33 degrees C), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal white matter 5 days after ischemia. Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41 +/- 20 vs 18 +/- 11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14 +/- 12 vs 91 +/- 51, P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4 +/- 6 vs 38 +/- 18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24 +/- 12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.     

Kainic acid-induced generalized seizures in cats--microinjection into caudate nucleus]

Electroencephalographic and behavioral changes were observed after 2 micrograms of kainic acid (KA) injection through a chronically implanted cannula into unilateral caudate nucleus (CN) of freely moving and non-anesthetized cats. The control group showed no changes on EEG or behavior during the observation period. In KA group, from 2 to 5 minutes after KA injection, the cats showed contralateral circling. On EEG, focal spikes were elicited at the injected site of the right CN. From 15 to 25 minutes after the injection, secondarily generalized seizures were observed on EEG repeatedly. However, the behavioral change was not remarkable and only the behavioral arrest was observed during the electrographic generalized seizure. From 6 to 8 hours after injection, they showed clonic seizure of the contralateral hindlimb followed by generalized tonic-clonic convulsion. These seizures were frequent during 6 to 16 hours after injection. However, these seizures subsided within 48 hours after the injection and the cats became normal afterward. Histopathological examination revealed focal pyknosis and gliosis only at the injection site of caudate nucleus. The results suggested that an epileptogenic focus of the caudate nucleus demonstrated a rapid evolution from the focal seizure status to the secondarily generalized seizure status. This fact explains that the caudate nucleus may be a possible key structure as a relay nucleus for the secondary generalization of a focal seizure.     

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.     

The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury.

Large-conductance, calcium-activated potassium (maxi-K) channels regulate neurotransmitter release and neuronal excitability, and openers of these channels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcome after lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized Sprague-Dawley rats (n = 142) were subjected to moderate FP brain injury (n = 88) or surgery without injury (n = 54) and were randomized to receive a bolus of 0.1 mg/kg BMS-204352 (n = 26, injured; n = 18, sham), 0.03 mg/kg BMS-204352 (n = 25, injured; n = 18, sham), or 2% dimethyl sulfoxide (DMSO) in polyethylene glycol (vehicle, n = 27, injured; n = 18, sham) at 10 minutes postinjury. One group of rats was tested for memory retention (Morris water maze) at 42 hours postinjury, then killed for evaluation of regional cerebral edema. A second group of injured/sham rats was assessed for neurologic motor function from 48 hours to 2 weeks postinjury and cortical lesion area. Administration of 0.1 mg/kg BMS-204352 improved neurologic motor function at 1 and 2 weeks postinjury (P < 0.05) and reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus, and adjacent cortex (P < 0.05). Administration of 0.03 mg/kg BMS-204352 significantly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No effects on cognitive function or cortical tissue loss were observed with either dose. These results suggest that the novel maxi-K channel opener BMS-204352 may be selectively beneficial in the treatment of experimental TBI.     

Suppression of postischemic epileptiform activity with MK-801 improves neural outcome in fetal sheep.

To determine the effect of suppression of epileptiform activity that develops after hypoxic-ischemic injury in the immature brain, chronically instrumented near-term fetal sheep (119-133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3-mg/kg bolus of MK-801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real-time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 +/- 2 to 30 +/- 3 hours in the control group was completely suppressed in the MK-801-treated group. The onset of secondary cortical edema was delayed from 9.4 +/- 1.1 hours to 14.8 +/- 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N-methyl-D-aspartate-mediated epileptiform activity that develops after a global hypoxic-ischemic insult worsens neuronal outcome in the immature brain.     

Characterization of postischemic behavioral deficits in gerbils with and without hypothermic neuroprotection

Five minutes of global ischemia in gerbil results in delayed hippocampal CA1 neuronal degeneration, which is accompanied by working memory impairments and hyperactivity in novel environments. In this study, postischemic activity was characterized in familiar and in novel environments to determine whether hyperactivity was due to impaired spatial habituation or another form of motor hyperactivity. This study also determined whether 6-h delayed hypothermia, which reduces CA1 neuronal injury, would attenuate functional impairments. Gerbils were subjected to 5 min of normothermic ischemia or sham operation 2 days following implantation of brain temperature probes. One of two ischemic groups was cooled (>48 h) starting at 6-h postischemia. Locomotor activity in a familiar cage was measured for 6 days while activity in three novel environments was intermittently measured on days 4, 5 and 6. Open field behavior and working memory in a T-maze were also assessed. Untreated ischemia caused marked hyperactivity in the familiar cage on day 1, which reverted to near-normal by day 2. Nonetheless, these gerbils showed hyperactivity during novel environment sessions on days 4–6. This maze behavior, which predicted hippocampal CA1 injury, was not due to different habituation rates nor baseline hyperactivity. Conversely, open field sessions on day 8 revealed ischemic habituation rate deficits. Ischemia also impaired working memory in the T-maze. Delayed hypothermia, which reduced neuronal loss in the CA1 sector to 12% from 81%, reduced all functional impairments. Ischemic gerbils quickly developed spontaneous locomotion hyperactivity that returned to near-normal after 1 day. This motor hyperactivity did not explain the elevated activity found with delayed testing in novel environments. Regardless, only the open field test on day 8 revealed a habituation-like deficit.     

Does Status Epilepticus Influence the Motor Development of Immature Rats?

Summary: Purpose : To study the effect of severe status epilepticus (SE) on the motor development of rats.
Methods : SE was induced in 12-day-old rats (P12 group) and 25-day-old rats (P25 group) using the lithium-pilocarpine model. Seizures were interrupted after 2 hours by paraldehyde with an intraperitoneal dose of 0.3 or 0·6 mL/kg, respectively. Starting 3 days after SE, all animals were repeatedly exposed to a battery of motor and behavioral tests, including the bar-holding test, rotarod test, and open field test.
Results : In P12 animals, motor impairment occurred 2 months after SE, when significantly worse performance in the rotarod test was found. No difference between controls and experimental rats was found in any other test used. In contrast, P25 animals were significantly poorer in the bar-holding test from postnatal day 34 until adulthood. In open field study, P25 rats were found to be hyperactive during the whole period of testing, whereas P12 animals exhibited an initial period of hypoactivity (in the first test) that was replaced by hyperactivity that lasted until 2 months of age. In the last test performed at the age of 98 days, experimental P12 animals were again less active than age-matched controls.
Conclusions : Animals of both age groups exhibited permanent changes of motor performance; however, both the pattern and the time course of these changes was related to age when SE was elicited.     

Influence of nitric oxide synthase inhibitor on gerbil behavior after hyperbaric oxygen-induced convulsion★

BACKGROUND:Studies have reported that nitric oxide synthase (NOS) inhibitor can prolong the latency of hyperbaric oxygen-induced convulsion (HBOC). However, there are very few reports addressing the influence of NOS inhibitor on mental behavior. OBJECTIVE: To investigate behavioral changes after HBOC in gerbils, as well as the influence of NOS inhibitor. DESIGN, TIME AND SETTING: Randomized experiments were performed in the Laboratory of Hyperbaric Pressure and Diving Physiology, Naval Medical Research Inst...     

新生大鼠缺氧缺血性脑损伤后CIRP表达与意义

目的观察新生大鼠缺氧缺血性脑损伤(HIBD)后冷诱导RNA结合蛋白(CIRP)表达的变化情况。方法将40只7日龄新生SD大鼠随机分为假手术组和HIBD组,分别采用real-time PCR及免疫组织化学方法检测假手术组和HIBD后不同时间点(6、12、24和48h)CIRP在大鼠脑皮质与海马表达的变化。结果利用免疫组化和real-time PCR检测发现,大鼠脑皮质的CIRP蛋白和CIRP mRNA表达呈持续降低趋势,HIBD后6、12 h开始减少;24~48h下降更为明显。海马CIRP蛋白和CIRP mRNA表达则表现为6 h先升48h后降。结论CIRP参与了新生大鼠脑缺氧缺血的应激过程,可能与缺氧缺血性脑损伤后的脑水肿及神经元凋亡相关。     

Hypoxia—ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum

The neonatal striatum degenerates after hypoxia–ischemia (H-I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration after H-I. Newborn piglets were subjected to 30 minutes of hypoxia (arterial O₂ saturation, 30%) and then 7 minutes of airway occlusion (O₂ saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putaminal neurons were injured, without differing significantly thereafter, but neuronal densities were reduced progressively (21–44%). By DNA nick-end labeling, the number of dying putaminal cells per square millimeter was increased maximally at 24 to 48 hours. Glial fibrillary acidic protein–positive cell body densities were reduced 48 to 55% at 24 to 48 hours but then recovered by 96 hours. Early postischemia, subsets of astrocytes had fragmented DNA; later postischemia, subsets of astrocytes proliferated. By immunocytochemistry, glutamate transporter 1 (GLT1) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid carrier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels were 85% and 45% of control, respectively, at 24 hours of recovery. Thus, astroglial and neuronal injury occurs rapidly in H-I newborn striatum, with early gliodegeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.     

Electroencephalogram confirmatory rate in neonatal seizures

The electroencephalogram (EEG) is confirmatory in 70% of children and adults with seizures, although gestation- and etiology-specific EEG confirmatory rates in neonates have not been well defined. All neonates treated for seizures and who underwent EEG were identified from 4,575 neonates admitted between 1985 and 1996 to a neonatal intensive care unit. The relationship between EEG findings (epileptiform discharges and background abnormalities) and gestation, mortality rate, and seizure etiology was examined using the Student t test. One hundred eighty-three neonates treated for seizures underwent a total of 352 EEGs: 144 of these neonates (79%) had an abnormal EEG (epileptiform discharges in 113 (60%) and nonepileptiform background abnormalities in 31). The EEG confirmatory rate increased with gestation (63% at 28 weeks vs 77% at term, P < 0.02). Etiology for seizures also influenced the EEG confirmatory rate: central nervous system (CNS) infection 95% (P < 0.05), hypoxic-ischemic encephalopathy 80% (P < 0.05), germinal matrix-intraventricular hemorrhage 65%, and CNS malformations 65%. The EEG confirmatory rate was predictive of neonatal mortality (19% vs 6%, P < 0.03). The EEG was directly confirmatory (epileptiform discharges) in 60% and supportive (nonepileptiform background abnormalities) in a further 17% of neonates with seizures. Gestation and etiology influence the EEG confirmatory rate in neonatal seizures.     

Moderate hypothermia in neonatal encephalopathy: efficacy outcomes

Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury, but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth. This study reports a multicenter, randomized, controlled, pilot trial of moderate systemic hypothermia (33 degrees C) vs normothermia (37 degrees C) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event. The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers, and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vineland tests between normothermic and hypothermic groups. Thirty-two hypothermic and 33 normothermic neonates were enrolled. The entry criteria selected a severely affected group of neonates, with 77% Sarnat stage III. Ten hypothermia (10/32, 31%) and 14 normothermia (14/33, 42%) patients expired. Controlling for treatment group, outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers (odds ratio 10.7, 95% confidence interval 1.3-90). Severely abnormal motor scores (Psychomotor Development Index < 70) were recorded in 64% of normothermia patients and in 24% of hypothermia patients. The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group (52%) than the normothermia group (84%) (P = 0.019). Although these results need to be validated in a large clinical trial, this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury.     

Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats

Sprague-Dawley neonatal rats within 7 days after birth were used in this study. The left common carotid artery was occluded and rats were housed in an 8% O2 environment for 2 hours to establish a hypoxic-ischemic brain damage model. 17β-estradiol (1 × 10-5 M) was injected into the rat abdominal cavity after the model was successfully established. The left hemisphere was obtained at 12, 24, 48, 72 hours after operation. Results showed that malondialdehyde content in the left brain of neonatal rats gradually increased as modeling time prolonged, while malondialdehyde content of 17β-estrodial-treated rats significantly declined by 24 hours, reached lowest levels at 48 hours, and then peaked at 72 hours after injury. Nicotinamide-adenine dinucleotide phosphate histochemical staining showed the nitric oxide synthase-positive cells and fibers dyed blue/violet and were mainly distributed in the cortex, hippocampus and medial septal nuclei. The number of nitric oxide synthase-positive cells peaked at 48 hours and significantly decreased after 17β-estrodial treatment. Our experimental findings indicate that estrogen plays a protective role following hypoxic-ischemic brain damage by alleviating lipid peroxidation through reducing the expression of nitric oxide synthase and the content of malondialdehyde.