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

Geocadin, Romergryko G.; Malhotra, Amit D.; Tong, Shanbao; Seth, Akhil K.; Moriwaki, Goroku; Hanley, Daniel F.; Thakor, Nitish V.

doi:10.1016/j.brainres.2005.04.046

Cited by 19 publications

(17 citation statements)

References 41 publications

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“…Neurological function was evaluated in the rats at 24, 48 and 72 h post-resuscitation using a neurological deficit scale (NDS) scoring system (score range, 0–100; score 0, normal; score 100, brain dead; Table I) (13,14). …”

Section: Methodsmentioning

confidence: 99%

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Sui

2014

Experimental and Therapeutic Medicine

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The aim of the present study was to determine the effects of ulinastatin (UTI) on brain injury in rats subjected to cardiopulmonary resuscitation (CPR) following asphyxial cardiac arrest (CA) and identify the underlying mechanisms. In total, 100 healthy male Wistar rats were randomly divided into control and treatment groups (n=50). After 4 min of asphyxial CA, all the rats were immediately subjected to CPR. The treatment group animals were administered 15 mg/kg UTI at the onset of resuscitation. The mortality rate in the two groups was recorded at 24 h post-resuscitation. In addition, neurological function was evaluated at 24, 48 and 72 h post-resuscitation using a neurological deficit scale (NDS). Furthermore, the effects of UTI on the Toll-like receptor 4 (TLR4) signaling pathway in brain tissues were determined by assessing TLR4 mRNA expression, nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels at 1, 3, 6, 12, 24, 48 and 72 h post-resuscitation. After 24 h, the mortality rate significantly decreased in the treatment group when compared with the control animals (10 vs. 30%; P<0.05). Additionally, an overt improvement was observed in the NDS score following UTI treatment when compared with the control (P<0.01). Finally, statistically significant decreases in the levels of TLR4 mRNA expression, NF-κB activity and TNF-α and IL-6 were observed in the treatment group at each time point (P<0.01). Therefore, UTI treatment at the onset of CPR significantly inhibits the TLR4 signaling pathway, thereby alleviating the inflammatory responses following resuscitation and improving neurological function.

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Section: Methodsmentioning

confidence: 99%

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Sui

2014

Experimental and Therapeutic Medicine

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“…While we have previously demonstrated that histopathological markers for ischemic cell death correlate with qEEG and NDS measures (26,37,45), we also acknowledge that postmortem histological markers in rats have been a poor indicator of clinical significance in human trials of the same agents and have been less predictive than early behavioral assessments (46)(47)(48). As such, we put more emphasis on functional outcome and realtime biological measures of recovery (qEEG) as a means to clinical translation.…”

Section: Discussionmentioning

confidence: 99%

Early electrophysiologic markers predict functional outcome associated with temperature manipulation after cardiac arrest in rats

Jia

Koenig

Nickl

et al. 2008

Critical Care Medicine

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Objective-Therapeutic hypothermia after cardiac arrest improves survival and functional outcomes, whereas hyperthermia is harmful. The optimal method of tracking the effect of temperature on neurologic recovery after cardiac arrest has not been elucidated. We studied the recovery of cortical electrical function by quantitative electroencephalography after 7-min asphyxial cardiac arrest, using information quantity (IQ). Design-Laboratory investigation.Setting-University medical school and animal research facility. Subjects-A total of 28 male Wistar rats.Interventions-Using an asphyxial cardiac arrest rodent model, we tracked quantitative electroencephalography of 6-hr immediate postresuscitation hypothermia (at 33°C), normothermia (37°C), or hyperthermia (39°C) (N=8 per group). Neurological recovery was evaluated using the Neurological Deficit Score. Four rats were included as a sham control group. Measurements and MainResults-Greater recovery of IQ was found in rats treated with hypothermia (IQ=0.74), compared to normothermia (IQ=0.60) and hyperthermia (IQ=0.56) (p<. 001). Analysis at different intervals demonstrated a significant separation of IQ scores among the temperature groups within the first 2 hrs postresuscitation (p<.01). IQ values of >0.523 at 60 mins postresuscitation predicted good neurological outcome (72-hr Neurological Deficit Score of≥60) with a specificity of 100% and sensitivity of 81.8%. IQ was also significantly lower in rats that died prematurely compared to survivors (p<.001). IQ values correlated strongly with 72-hr Neurological Deficit Score as early as 30 mins post-cardiac arrest (Pearson correlation 0.735, p<.01) and maintained a significant association throughout the 72-hr experiment. No IQ difference was noted in sham rats with temperature manipulation. Approximately 164,600 cardiac arrests (CAs) occur in the United States each year (1). Among initial survivors, 80% remain comatose after resuscitation (2) and neurological complications represent the leading cause of disability (3,4). The ischemic brain is sensitive to temperature, such that small differences can critically influence neuropathological outcomes (5). Hyperthermia has been demonstrated to worsen ischemic outcome and is associated with increased brain injury in animal models (5,6) and clinical studies (7-9). On the other hand, induced hypothermia to 32-34°C is recommended for comatose survivors of CA (10,11) and was recently shown to significantly mitigate brain injury in animal models (12)(13)(14) and clinical trials (15-18). NIH Public AccessNeurological monitoring of comatose CA survivors is complicated by the requirement for sedative and paralytic agents, particularly in patients who are treated with hypothermia. Comatose CA survivors are typically cared for by nurses and physicians in general or cardiac intensive care units with little specialized training in neurological examination. In addition, the ability to detect even major changes in brain function in comatose patients is limited. Electroencephalograp...

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“…These areas were chosen because CA-1 is selectively vulnerable to global cerebral ischemia in animals and humans studies and the cerebral cortex is closely related to functional outcome and EEG changes 11,18,26,38,39 . Stereologic technique was performed in the predefined set of random, non-overlapping microscope fields using Adreas Stereo Investigator software 5.05.4 (MicroBrightField, Williston, VT) to estimate the degree of neuronal injury.…”

Section: Quantitative Brain Histopathological Damage Scoring (Hds)mentioning

confidence: 99%

Improving neurological outcomes post-cardiac arrest in a rat model: Immediate hypothermia and quantitative EEG monitoring

Jia¹,

Koenig²,

Shin³

et al. 2008

Resuscitation

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133

136

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SummaryObjectives-Therapeutic hypothermia (TH) after cardiac arrest (CA) improves outcomes in a fraction of patients. To enhance the administration of TH, we studied brain electrophysiological monitoring in determining the benefit of early initiation of TH compared to conventional administration in a rat model. Methods-Using an asphyxial CA model, we compared the benefit of immediate hypothermia (IH, T=33°C, immediately post-resuscitation, maintained 6 hours) to conventional hypothermia (CH, T=33°C, starting 1 hour post-resuscitation, maintained 12 hours) via surface cooling. We tracked quantitative EEG using relative entropy (qEEG) with outcome verification by serial Neurological Deficit Score (NDS) and quantitative brain histopathological damage scoring (HDS). Thirty-two rats were divided into 4 groups based on CH/IH and 7/9-minute duration of asphyxial CA. Four sham rats were included for evaluation of the effect of hypothermia on qEEG.Results-The 72-hour NDS of the IH group was significantly better than the CH group for both 7-minute (74/63; Median, IH/CH, p<0.001) and 9-minute (54/47, p=0.022) groups. qEEG showed greater recovery with IH (p<0.001) and significantly less neuronal cortical injury by HDS (IH: 18.9 ±2.5% versus CH: 33.2±4.4%, p=0.006). The 1-hour post-resuscitation qEEG correlated well with 72-hour NDS (p<0.05) and 72-hour behavioral subgroup of NDS (p<0.01). No differences in qEEG were noted in the sham group. *Corresponding author: Xiaofeng JIA MD, PhD, CRB II Building 3M-South, 1550 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA, Telephone number: +1-410-502-2820, Fax: +1-410-502-7869, E-mail address: xjia1@jhmi.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Portions of this work were previously presented in 4 th Annual Meeting of the Neurocritical Care Society in Baltimore, MD (November 2006) and at the 36 th Annual Meeting of the Society for Neuroscience at Atlanta, Georgia (October 2006) where it was selected for the lay language summary press book. Conflict of interest statementThere are no conflicts of interest in this study. Conclusions-Immediate but shorter hypothermia compared to CH leads to better functional outcome in rats after 7-and 9-minute CA. The beneficial effect of IH was readily detected by neuroelectrophysiological monitoring and histological changes supported the value of this observation. NIH Public Access

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

Cited by 19 publications

References 41 publications

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation

Early electrophysiologic markers predict functional outcome associated with temperature manipulation after cardiac arrest in rats

Improving neurological outcomes post-cardiac arrest in a rat model: Immediate hypothermia and quantitative EEG monitoring

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