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Aim: Around six percent of comatose patients after cardiac arrest have a Cerebral Performance Categories score of three (CPC3) at six months after the arrest, classified as severe neurological disability. There is limited knowledge regarding the likelihood of further recovery in the cognitive, emotional, and quality of life domains. We aimed to estimate the probability of recovery towards independency., Methods: From a prospective Registry on comatose cardiac arrest patients admitted between 2013 and 2017 in two Dutch hospitals, we included patients with a CPC3 at six months after cardiac arrest. We followed patients up to November 2023. The primary outcome measure was the CPC score at time of follow up. Secondary outcomes were scores on questionnaires on cognition, mood, and quality of life according to the minimal dataset of acquired brain injury., Results: In our cohort of 667 patients, 29 (4.3%) had a CPC3 score at six months (median age 68 years, 83% male). At a median time of eight years after cardiac arrest, sixteen patients had died. Twelve of thirteen alive patients still had a CPC3 score (92%) and one a CPC2 (8%). Seven patients agreed with further interviewing, one showed independency in activities of daily living (14%). Six patients (86%) reported limitations due to physical and one (14%) due to emotional problems. All had severe cognitive impairment. Six (86%) missed cognitive rehabilitation., Conclusion: Our study shows that while the probability of recovery towards independence for patients with severe neurological disability at six months after cardiac arrest is limited, most long-term survivors are satisfied with their quality of life., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘J. Hofmeijer is supported by a Dutch governmental grant from ZonMW (grant number 95105001). J. Hofmeijer is supported by a grant from the Dutch Heart Association (grant number CEI 2018T070). Furthermore there is nothing to declare’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Approximately half of cardiac arrest survivors have persistent cognitive impairment. Guidelines recommend early screening to identify patients at risk for cognitive impairment, but there is no consensus on the best screening method. We aimed to identify quantitative EEG measures relating with short- and long-term cognitive function after cardiac arrest for potential to cognitive outcome prediction., Methods: We analyzed data from a prospective longitudinal multicenter cohort study designed to develop a prediction model for cognitive outcome after cardiac arrest. For the current analysis, we used twenty-minute EEG registrations from 80 patients around one week after cardiac arrest. We calculated power spectral density, normalized alpha-to-theta ratio (nATR), peak frequency, and center of gravity (CoG) of this peak frequency. We related these with global cognitive functioning (scores on the Montreal Cognitive Assessment (MoCA)) at one week, three and twelve months follow-up with multivariate mixed effect models, and with performance on standard neuropsychological examination at twelve months using Pearson correlation coefficients., Results: Each individual EEG parameter related to MoCA at one week (β nATR  = 7.36; P < 0.01; β peak frequency = 1.73, P < 0.01; β CoG  = -9.88, P < 0.01). The nATR also related with the MoCA at three months ((β nATR  = 2.49; P 0.01). No EEG metrics significantly related to the MoCA score at twelve months. nATR and peak frequency related with memory performance at twelve months. Results were consistent in sensitivity analyses., Conclusion: Early resting-state EEG parameters relate with short-term global cognitive functioning and with memory function at one year after cardiac arrest. Additional predictive values in multimodal prediction models need further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Rhythmic and periodic patterns (RPPs) on the electroencephalogram (EEG) in comatose patients after cardiac arrest have been associated with high case fatality rates. A good neurological outcome according to the Cerebral Performance Categories (CPC) has been reported in up to 10% of cases. Data on cognitive, emotional, and quality of life outcomes are lacking. We aimed to provide insight into these outcomes at one-year follow-up., Methods: We assessed outcome of surviving comatose patients after cardiac arrest with RPPs included in the 'treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation' (TELSTAR) trial at one-year follow-up, including the CPC for functional neurological outcome, a cognitive assessment, the hospital anxiety and depression scale (HADS) for emotional outcomes, and the 36-item short-form health survey (SF-36) for quality of life. Cognitive impairment was defined as a score of more than 1.5 SD below the mean on ≥ 2 (sub)tests within a cognitive domain., Results: Fourteen patients were included (median age 58 years, 21% female), of whom 13 had a cognitive impairment. Eleven of 14 were impaired in memory, 9/14 in executive functioning, and 7/14 in attention. The median scores on the HADS and SF-36 were all worse than expected. Based on the CPC alone, 8/14 had a good outcome (CPC 1-2)., Conclusion: Nearly all cardiac arrest survivors with RPPs during the comatose state have cognitive impairments at one-year follow-up. The incidence of anxiety and depression symptoms seem relatively high and quality of life relatively poor, despite 'good' outcomes according to the CPC., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prognostication of comatose patients after cardiac arrest aims to identify patients with a large probability of favourable or unfavouble outcome, usually within the first week after the event. Electroencephalography (EEG) is a technique that is increasingly used for this purpose and has many advantages, such as its non-invasive nature and the possibility to monitor the evolution of brain function over time. At the same time, use of EEG in a critical care environment faces a number of challenges. This narrative review describes the current role and future applications of EEG for outcome prediction of comatose patients with postanoxic encephalopathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: To increase efficiency of continuous EEG monitoring for prognostication of neurological outcome in patients after cardiac arrest, we investigated the reliability of EEG in a four-electrode frontotemporal (4-FT) montage, compared to our standard nine-electrode (9-EL) montage., Methods: EEG recorded with Ag/AgCl cup-electrodes at 12 and/or 24 h after cardiac arrest of 153 patients was available from a previous study. 220 EEG epochs of 5 minutes were reexamined in a 4-FT montage according to the ACNS criteria. Background classification was compared to the available 9-EL classification using Cohens kappa. Reliability for prognostication was assessed in 151 EEG epochs at 24 h after CA using sensitivity and specificity for prediction of poor (cerebral performance categories (CPC) 3-5) and good (CPC 1-2) neurological outcome., Results: Agreement for EEG background classification between the two montages was substantial with a kappa of 0.85 (95%-CI 0.81-0.90). Specificity for prediction of poor outcome was 100% (95%-CI 95-100) for both montages, sensitivity was 31% (95%-CI 21-43) for the 4-FT montage and 35% (95%-CI 24-47) for the 9-EL montage. Good outcome was predicted with 65% specificity (95%-CI 53-76) and 81% sensitivity (95%-CI 71-89) for the 4-FT montage, similar to the 9-EL montage., Conclusion: In this cohort, EEG background patterns determined in a four-electrode frontotemporal montage predict both poor and good outcome after CA with similar reliability. Our results may contribute to decreasing the workload of EEG monitoring in patients after CA without compromising reliability of outcome prediction. However, validation in a larger cohort is necessary, as is a multimodal approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome., Design: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR) trial., Setting: Eleven ICUs in the Netherlands and Belgium., Patients: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring., Interventions: Anti-seizure medication vs no anti-seizure medication in addition to standard care., Measurements and Main Results: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32)., Conclusions: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Cardiac arrest survivors are at risk of long-term cognitive impairment. Patients with cognitive impairments do not always have cognitive complaints and vice versa. Not reporting cognitive complaints could be caused by a lack of awareness. We hypothesized that caregivers report more cognitive failures than patients, indicating patients' lack of insight into cognitive functioning., Methods: This is a secondary analysis of the Activity and Life After Survival of Cardiac Arrest study on survivors of cardiac arrest and their caregivers. They were assessed at two weeks, three months, and one year after cardiac arrest. At each time point, the patient and the caregiver filled out the cognitive failure questionnaire (CFQ) regarding the patient. We analysed the correlation, intraclass correlation, and self-proxy discrepancy between patients and caregivers on the CFQ over time., Results: One-hundred-and-nineteen cardiac arrest survivors (mean age = 60, 85 % male) and their caregivers were included. The CFQ scores of the patients and caregivers were equally low. The correlation (T1 r = 0.31; T2 r = 0.40; T3 r = 0.55) and intraclass correlation (T1 r = 0.48; T2 r = 0.56; T3 r = 0.71) between patient and caregiver increased over time., Conclusion: This study does not support a lack of awareness of cognitive impairments by long-term cardiac arrest survivors. Future research may focus on alternative explanations for why patients have less cognitive complaints than expected based on the frequency of cognitive impairments. Possible explanations include a response shift., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To assess neurological outcome after targeted temperature management (TTM) at 33 °C vs. 36 °C, stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h., Design: Post hoc analysis of prospective cohort study., Setting: Five Dutch Intensive Care units., Patients: 479 adult comatose post-cardiac arrest patients., Interventions: TTM at 33 °C (n = 270) or 36 °C (n = 209) and continuous EEG monitoring., Measurements and Main Results: Outcome according to the cerebral performance category (CPC) score at 6 months post-cardiac arrest was similar after 33 °C and 36 °C. However, when stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h after cardiac arrest, the proportion of good outcome (CPC 1-2) in patients with moderate encephalopathy was significantly larger after TTM at 33 °C (66% vs. 45%; Odds Ratios 2.38, 95% CI = 1.32-4.30; p = 0.004). In contrast, with mild encephalopathy, there was no statistically significant difference in the proportion of patients with good outcome between 33 °C and 36 °C (88% vs. 81%; OR 1.68, 95% CI = 0.65-4.38; p = 0.282). Ordinal regression analysis showed a shift towards higher CPC scores when treated with TTM 33 °C as compared with 36 °C in moderate encephalopathy (cOR 2.39; 95% CI = 1.40-4.08; p = 0.001), but not in mild encephalopathy (cOR 0.81 95% CI = 0.41-1.59; p = 0.537). Adjustment for initial cardiac rhythm and cause of arrest did not change this relationship., Conclusions: Effects of TTM probably depend on the severity of encephalopathy in comatose patients after cardiac arrest. These results support inclusion of predefined subgroup analyses based on EEG measures of the severity of encephalopathy in future clinical trials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sjoukje Nutma, PhD candidate, has been paid by funding of ZonMW and Hersenstichting., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: The survival rate of out-of-hospital cardiac arrest (OHCA) patients has increased over the past decades. This gives rise to a growing number of patients with hypoxic-ischemic brain damage and cognitive impairment. Currently, cognitive impairment is underdiagnosed in OHCA patients. There is a need for a validated cognitive screening instrument to identify patients with cognitive impairment. This study aimed to examine the diagnostic value of the Montreal Cognitive Assessment (MoCA) in patients after OHCA., Methods: Survivors (age ≥ 18 years) of OHCA completed the MoCA and a gold standard neuropsychological test battery, including tests for memory, attention, perception, language, reasoning, and executive functioning, at around one year after OHCA. Results of the MoCA are related to the results of the neuropsychological test battery. Analyses of diagnostic accuracy included receiver operating characteristics and calculation of predictive values., Results: We included 54 OHCA survivors (mean age = 57.3, 74% male). The area under the curve (AUC) was 0.8, 95% CI [0.67, 0.93]. The MoCA showed excellent sensitivity of 86%, 95% CI [57, 98] and adequate specificity of 70.0%, 95% CI [53, 83] to detect cognitive impairment at the regular cut-off score of 26. The positive predictive value of the MoCA was 50%, 95% CI [30, 70] and the negative predictive value was 93%, 95% CI [76, 99]., Conclusion: This study shows that the MoCA may be a valid cognitive screening instrument for use in the OHCA patient population., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To elicit preferences for prognostic information, attitudes towards withdrawal of life-sustaining treatment (WLST) and perspectives on acceptable quality of life after post-anoxic coma within the adult general population of Germany, Italy, the Netherlands and the United States of America., Methods: A web-based survey, consisting of questions on respondent characteristics, perspectives on quality of life, communication of prognostic information, and withdrawal of life-sustaining treatment, was taken by adult respondents recruited from four countries. Statistical analysis included descriptive analysis and chi2-tests for differences between countries., Results: In total, 2012 respondents completed the survey. In each country, at least 84% indicated they would prefer to receive early prognostic information. If a poor outcome was predicted with some uncertainty, 37-54% of the respondents indicated that WLST was not to be allowed. A conscious state with severe physical and cognitive impairments was perceived as acceptable quality of life by 17-44% of the respondents. Clear differences between countries exist, including respondents from the U.S. being more likely to allow WLST than respondents from Germany (OR = 1.99, p < 0.001) or the Netherlands (OR = 1.74, p < 0.001) and preferring to stay alive in a conscious state with severe physical and cognitive impairments more than respondents from Italy (OR = 3.76, p < 0.001), Germany (OR = 2.21, p < 0.001), or the Netherlands (OR = 2.39, p < 0.001)., Conclusions: Over one-third of the respondents considered WLST unacceptable when there is any remaining prognostic uncertainty. Respondents had a more positive perspective on acceptable quality of life after coma than what is currently considered acceptable in medical literature. This indicates a need for a closer look at the practice of WLST based on prognostic information, to ensure responsible use of novel prognostic tests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Electroencephalography (EEG) is an important tool for neurological outcome prediction after cardiac arrest. However, the complexity of continuous EEG data limits timely and accurate interpretation by clinicians. We develop a deep neural network (DNN) model to leverage complex EEG trends for early and accurate assessment of cardiac arrest coma recovery likelihood., Methods: We developed a multiscale DNN combining convolutional neural networks (CNN) and recurrent neural networks (long short-term memory [LSTM]) using EEG and demographic information (age, gender, shockable rhythm) from a multicenter cohort of 1,038 cardiac arrest patients. The CNN learns EEG feature representations while the multiscale LSTM captures short-term and long-term EEG dynamics on multiple time scales. Poor outcome is defined as a Cerebral Performance Category (CPC) score of 3-5 and good outcome as CPC score 1-2 at 3-6 months after cardiac arrest. Performance is evaluated using area under the receiver operating characteristic curve (AUC) and calibration error., Results: Model performance increased with EEG duration, with AUC increasing from 0.83 (95% Confidence Interval [CI] 0.79-0.87 at 12h to 0.91 (95%CI 0.88-0.93) at 66h. Sensitivity of good and poor outcome prediction was 77% and 75% at a specificity of 90%, respectively. Sensitivity of poor outcome was 50% at a specificity of 99%. Predicted probability was well matched to the observation frequency of poor outcomes, with a calibration error of 0.11 [0.09-0.14]., Conclusions: These results demonstrate that incorporating EEG evolution over time improves the accuracy of neurologic outcome prediction for patients with coma after cardiac arrest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: To establish incidence, phenotype, long-term functional outcome, and early EEG predictors of delirium after cardiac arrest., Methods: This is an ad hoc analysis of a prospective cohort study on outcome prediction of comatose patients after cardiac arrest. Patients with recovery of consciousness, who survived until hospital discharge, were subdivided in groups with and without delirium based on psychiatric consultation. Delirium phenotype and medical treatment were retrieved from patient files. All other data were prospectively collected. We used univariate analyses of baseline and early EEG characteristics for identification of possible delirium predictors. Association of delirium with neurological recovery at six months was analyzed with multinomial logistic regression analysis., Results: Of 233 patients, 141 survived until hospital discharge, of whom 47 (33%) were diagnosed with delirium. There were no differences in baseline characteristics between patients with and without delirium. All delirious patients were treated with relatively high dosages of psychopharmaceuticals, mostly haloperidol and benzodiazepine agonists. Prevalent characteristics were disturbed cognition, perception and psychomotor functioning (98%). Half of the patients had language disorders or shouting. Delirium was associated with longer ICU and hospital admission, and more frequent discharge to rehabilitation centre or nursing home. There was a trend towards poorer neurological recovery. EEG measurements within 12 h after cardiac arrest could predict delirium with 91% specificity and 40% sensitivity., Discussion: Delirium is common after cardiac arrest, and probably leads to longer hospitalization and poorer outcome. Optimal treatment is unclear. Early EEG holds potential to identify patients at risk., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Depression after a stroke is a common complication that negatively influences stroke rehabilitation. Early identification, followed by adequate treatment of depression, improves recovery from stroke. To support early identification, the Post-stroke Depression Prediction Scale (DePreS) was developed to predict in the first week after stroke, the risk of depression in the second month. In this study we investigate the predictive accuracy of the DePreS in stroke patients., Methods: In this prospective multicenter observational study, hospitalized stroke patients were included from three stroke units in the Netherlands and Germany using consecutive sampling. In the first week after stroke, the predicted risk for depression was estimated with the DePreS. Two months after stroke, major depressive disorder was determined with the Composite International Diagnostic Interview., Results: Of the 93 included patients, 17 (18.3%) showed symptoms of major depressive disorder. With a cut-off value of ≥ 0, DePreS performed optimally with a sensitivity of 0.65 (95% CI 0.42-0.87), specificity of 0.74 (95% CI 0.64-0.84), positive predictive value of 0.35 (95% CI 0.19-0.52), and negative predictive value of 0.90 (95% CI 0.80-1.00). The AUC was 0.71 (95% CI 0.56-0.86)., Limitations: The generalizability of the study findings is limited to patients able to communicate adequately., Conclusions: This study demonstrates that the DePreS is an adequate instrument for early and reliable identification of stroke patients who are not at risk of MDD in the second months after stroke. This limits the need for structural diagnostic follow-up to patients with a high risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Early EEG patterns and SSEP responses are associated with neurological recovery of comatose patients with postanoxic encephalopathy after cardiac arrest. However, the nature and distribution of brain damage underlying the characteristic EEG and SSEP patterns are unknown. We relate EEG and SSEP findings with results from histological analyses of the brains of eleven non-survivors. With restoration towards continuous rhythms within 24 h after cardiac arrest, no signs of structural neuronal damage were observed. Absent SSEP responses were always accompanied by thalamic damage. Pathological burst suppression patterns were associated with a variable degree of neuronal damage to cortex, cerebellum and hippocampus. In patients with additional thalamic involvement, burst-suppression with identical bursts was observed, a characteristic EEG pattern presumably reflecting residual activity from a relatively isolated and severely compromised cortex., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Hypoxic-ischemic brain injury is the main cause of death and disability of comatose patients after cardiac arrest. Early and reliable prognostication is challenging. Common prognostic tools include clinical neurological examination and electrophysiological measures. Brain imaging is well established for diagnosis of focal cerebral ischemia but has so far not found worldwide application in this patient group., Objective: To review the value of Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) for early prediction of neurological outcome of comatose survivors of cardiac arrest., Methods: A literature search was performed to identify publications on CT, MRI or PET in comatose patients after cardiac arrest., Results: We included evidence from 51 articles, 21 on CT, 27 on MRI, 1 on CT and MRI, and 2 on PET imaging. Studies varied regarding timing of measurements, choice of determinants, and cut-off values predicting poor outcome. Most studies were small (n = 6-398) and retrospective (60%). In general, cytotoxic oedema, defined by a grey-white matter ratio <1.10, derived from CT, or MRI-diffusion weighted imaging <650 × 10 -6  mm 2 /s in >10% of the brain could differentiate between patients with favourable and unfavourable outcomes on a group level within 1-3 days after cardiac arrest. Advanced imaging techniques such as functional MRI or diffusion tensor imaging show promising results, but need further evaluation., Conclusion: CT derived grey-white matter ratio and MRI based measures of diffusivity and connectivity hold promise to improve outcome prediction after cardiac arrest. Prospective validation studies in a multivariable approach are needed to determine the additional value for the individual patient., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim of the Study: Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest., Methods: We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery (MFV MCA ) by transcranial Doppler. Arterial and jugular blood samples were used for calculation of the jugular venous-to-arterial CO 2 /arterial to-jugular venous O 2 content difference ratio., Results: After cardiac arrest, MFV MCA increased from 26.0[18.6-40.4]cm/sec on admission to 63.9[48.3-73.1]cm/sec after 72h (p<0.0001), with no significant differences between survivors and non-survivors (p=0.4853). The MFV MCA in controls was 59.1[52.8-69.0]cm/sec. The oxygen extraction fraction (O 2 EF) was 38.9[24.4-47.7]% on admission and decreased significantly to 17.3[12.1-26.2]% at 72h (p<0.0001). The decrease in O 2 EF was more pronounced in non-survivors (p=0.0173). O 2 EF in the control group was 35.4[32.4-38.7]%. The jugular bulb-arterial CO 2 to arterial-jugular bulb O 2 content difference ratio was >1 at all time points after cardiac arrest and did not change during admission, with no differences between survivors and non-survivors. Values in cardiac arrest patients were similar to those in normal subjects., Conclusions: In this study, low CBF after cardiac arrest is not associated with anaerobic metabolism. Hypoperfusion appears to be the consequence of a decrease of neuronal functioning and metabolic needs. Alternatively, hypoperfusion may decrease cerebral metabolism. Subsequently, metabolism increases in survivors, consistent with resumption of neuronal activity, whereas in non-survivors lasting low metabolism reflects irreversible neuronal damage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We aimed to establish a rat model of space-occupying hemispheric infarction to evaluate potential treatment strategies. For adequate timing of therapy in future experiments, we studied the development of tissue damage, edema formation, and perfusion over time with different MRI techniques. Permanent middle cerebral artery (MCA) occlusion was performed in 32 Fisher-344 rats. Forty-six MRI experiments including diffusion weighted (DW), T2-weighted (T2W), flow-sensitive alternating inversion recovery (FAIR) perfusion-weighted, and T1-weighted (T1W) imaging before and after gadolinium were performed at 1, 3, 8, 16, 24, and 48 h of ischemia. MCA occlusion consistently led to infarction of the complete MCA territory. Mortality was 75%. Lesion volumes as derived from apparent diffusion coefficient (ADC) and T2 maps increased to maximum values of 400+/-48 mm3 at 24 h and 420+/-54 mm3 at 48 h of ischemia, respectively. Midline shift peaked at 24 h. The area with diffusion-perfusion deficit decreased to a minimum at 24 h after onset of ischemia and perfusion of the contralateral hemisphere dropped at the same time point. Leakage of gadolinium through the blood-brain barrier in the entire infarct occurred within 3 h of ischemia. Permanent intraluminal MCA occlusion in Fisher-344 rats is an adequate model for space-occupying cerebral infarction. Rats may benefit from intervention aimed at reducing tissue shift and intracranial pressure (ICP), and at improving cerebral blood flow, if initiated before 24 h after MCA occlusion. The value of treatment modalities depending on an intact blood-brain barrier should be questioned.