scholarly journals Mild Hyperthermia Aggravates Glucose Metabolic Consequences in Repetitive Concussion

2020 ◽  
Vol 21 (2) ◽  
pp. 609
Author(s):  
Meghan Blaya ◽  
Jessie Truettner ◽  
Weizhao Zhao ◽  
Helen Bramlett ◽  
William Dalton Dietrich
Keyword(s):  
Brain Injury ◽  
Glucose Metabolism ◽  
Brain Temperature ◽  
Brain Regions ◽  
Cerebral Glucose Metabolism ◽  
Temperature Management ◽  
Diagnostic Tools ◽  
Neurological Outcomes ◽  
The Impact ◽  
The Brain

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability around the world. Mild TBI (mTBI) makes up approximately 80% of reported cases and often results in transient psychological abnormalities and cognitive disruption. At-risk populations for mTBI include athletes and other active individuals who may sustain repetitive concussive injury during periods of exercise and exertion when core temperatures are elevated. Previous studies have emphasized the impact that increased brain temperature has on adverse neurological outcomes. A lack of diagnostic tools to assess concussive mTBI limits the ability to effectively identify the post-concussive period during which the brain is uniquely susceptible to damage upon sustaining additional injury. Studies have suggested that a temporal window of increased vulnerability that exists corresponds to a period of injury-induced depression of cerebral glucose metabolism. In the current study, we sought to evaluate the relationship between repetitive concussion, local cerebral glucose metabolism, and brain temperature using the Marmarou weight drop model to generate mTBI. Animals were injured three consecutive times over a period of 7 days while exposed to either normothermic or hyperthermic temperatures for 15 min prior to and 1 h post each injury. A 14C-2-deoxy-d-glucose (2DG) autoradiography was used to measure local cerebral metabolic rate of glucose (lCMRGlc) in 10 diverse brain regions across nine bregma levels 8 days after the initial insult. We found that repetitive mTBI significantly decreased glucose utilization bilaterally in several cortical areas, such as the cingulate, visual, motor, and retrosplenial cortices, as well as in subcortical areas, including the caudate putamen and striatum, compared to sham control animals. lCMRGlc was significant in both normothermic and hyperthermic repetitive mTBI animals relative to the sham group, but to a greater degree when exposed to hyperthermic conditions. Taken together, we report significant injury-induced glucose hypometabolism after repetitive concussion in the brain, and additionally highlight the importance of temperature management in the acute period after brain injury.

scholarly journals The impact of a multi-domain intervention on cerebral glucose metabolism: analysis from the randomized ancillary FDG PET MAPT trial

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Julien Delrieu ◽  
Thierry Voisin ◽  
Laure Saint-Aubert ◽  
Isabelle Carrie ◽  
Christelle Cantet ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fdg Pet ◽  
Primary Outcome ◽  
Cognitive Stimulation ◽  
Cerebral Glucose Metabolism ◽  
Parahippocampal Gyrus ◽  
Cerebral Magnetic Resonance Imaging ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
The Impact

Abstract Background The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. Methods MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. Results The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. Conclusions MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. Trial registration ClinicalTrials.gov Identifier, NCT01513252.

Heart Rate and Neurological Outcomes in Patients Undergoing Targeted Temperature Management

2020 ◽  
pp. 088506662098250
Author(s):  
Chad M. Conner ◽  
William H. Perucki ◽  
Andre Gabriel ◽  
David M. O’Sullivan ◽  
Antonio B. Fernandez
Keyword(s):  
Heart Rate ◽  
Positive Association ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Neurological Outcomes ◽  
Neurologic Outcomes ◽  
Resuscitation Guidelines ◽  
The Mean ◽  
The Impact ◽  
The Relationship

Introduction: There is a paucity of data evaluating the impact of heart rate (HR) during Targeted Temperature Management (TTM) and neurologic outcomes. Current resuscitation guidelines do not specify a HR goal during TTM. We sought to determine the relationship between HR and neurologic outcomes in a single-center registry dataset. Methods: We retrospectively studied 432 consecutive patients who completed TTM (33°C) after cardiac arrest from 2008 to 2017. We evaluated the relationship between neurologic outcomes and HR during TTM. Pittsburgh Cerebral Performance Categories (CPC) at discharge were used to determine neurological recovery. Statistical analysis included chi square, Student’s t-test and Mann-Whitney U. A logistic regression model was created to evaluate the strength of contribution of selected variables on the outcome of interest. Results: Approximately 94,000 HR data points from 432 patients were retrospectively analyzed; the mean HR was 82.17 bpm over the duration of TTM. Favorable neurological outcomes were seen in 160 (37%) patients. The mean HR in the patients with a favorable outcome was lower than the mean HR of those with an unfavorable outcome (79.98 bpm vs 85.67 bpm p < 0.001). Patients with an average HR of 60-91 bpm were 2.4 times more likely to have a favorable neurological outcome compared to than HR’s < 60 or > 91 (odds ratio [OR] = 2.36, 95% confidence interval [CI] 1.61-3.46, p < 0.001). Specifically, mean HR’s in the 73-82 bpm range had the greatest rate of favorable outcomes (OR 3.56, 95% CI 1.95-6.50), p < 0.001. Administration of epinephrine, a history of diabetes mellitus and hypertension all were associated with worse neurological outcomes independent of HR. Conclusion: During TTM, mean HRs between 60-91 showed a positive association with favorable outcomes. It is unclear whether a specific HR should be targeted during TTM or if heart rates between 60-91 bpm might be a sign of less neurological damage.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

Investigation of Stress Wave Propagation in Brain Tissues Through the Use of Finite Element Method

2010 ◽  
Author(s):  
Biaobiao Zhang ◽  
W. Steve Shepard ◽  
Candace L. Floyd
Keyword(s):  
Finite Element ◽  
Wave Propagation ◽  
Brain Injury ◽  
Stress Wave ◽  
Brain Research ◽  
Complex Structure ◽  
Stress Wave Propagation ◽  
Wave Loads ◽  
The Impact ◽  
The Brain

Because axons serve as the conduit for signal transmission within the brain, research related to axon damage during brain injury has received much attention in recent years. Although myelinated axons appear as a uniform white matter, the complex structure of axons has not been thoroughly considered in the study of fundamental structural injury mechanisms. Most axons are surrounded by an insulating sheath of myelin. Furthermore, hollow tube-like microtubules provide a form of structural support as well as a means for transport within the axon. In this work, the effects of microtubule and its surrounding protein mediums inside the axon structure are considered in order to obtain a better understanding of wave propagation within the axon in an attempt to make progress in this area of brain injury modeling. By examining axial wave propagation using a simplified finite element model to represent microtubule and its surrounding proteins assembly, the impact caused by stress wave loads within the brain axon structure can be better understood. Through conducting a transient analysis as the wave propagates, some important characteristics relative to brain tissue injuries are studied.

Abstract 312: The Impact of Sedation on Quantitative Electroencephalogram Trends and Neurological Outcomes in a Mouse Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Takamitsu Ikeda ◽  
Yusuke Miyazaki ◽  
Eizo Marutani ◽  
Fumito Ichinose
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Neurological Function ◽  
Temperature Management ◽  
Vehicle Group ◽  
Altered Level ◽  
Eeg Activity ◽  
Neurological Outcomes ◽  
Significant Difference ◽  
The Impact

Introduction: The majority of patients resuscitated from cardiac arrest (CA) present in coma or with an altered level of consciousness. Although most CA survivors are sedated during targeted temperature management, the effects of sedation on post-arrest outcomes remain to be determined. Hypothesis: Sedation after CA improves neurological outcomes by modulating cerebral electrical activity and metabolism. Methods: Ten to 14 days after implantation of EEG transmitters, adult male C57BL/6J mice were subjected to CA and cardiopulmonary resuscitation (CPR). After return of spontaneous circulation (ROSC), mice received intravenous infusion of propofol, dexmedetomidine (DEX), or normal saline (vehicle) for 2 hours. Body temperature was maintained at 37°C, and was subsequently lowered to 33°C. Cerebral blood flow (CBF) was measured for 4 hours following ROSC. To quantify time-dependent EEG changes, we calculated the sum of the Delta, Theta, and Alpha band power in consecutive 12-hour intervals after ROSC (D 0-12 and D 12-24 , T 0-12 and T 12-24 , and A 0-12 and A 12-24 , respectively). Because the increase in fast EEG activity over time may reflect neurological recovery after CA, we compared the ratios of D 12-24 to D 0-12 , of T 12-24 to T 0-12 , and of A 12-24 to A 0-12 among groups. Results: As compared with vehicle-treated mice, propofol- or DEX-treated mice exhibited improved survival rate and neurological function after CA, though no difference was found between propofol- and DEX-treated mice. In the vehicle group, CBF was higher than the baseline after ROSC, while the increase in CBF was attenuated in the propofol and DEX group. The values of A 12-24 /A 0-12 and T 12-24 /T 0-12 were significantly higher in propofol- and DEX-treated mice than in vehicle-treated mice ( P = 0.017 and P = 0.004, respectively, propofol vs vehicle; P = 0.038 and P = 0.002, respectively, DEX vs vehicle), but there was no significant difference in D 12-24 /D 0-12 among groups. In all post-arrest mice, both A 12-24 /A 0-12 and T 12-24 /T 0-12 were positively correlated with better neurological function at 24 and 48 hours after CA. Conclusions: Post-arrest sedation was associated with a reduction in CBF and a greater recovery of fast EEG activity after CA, and improved neurological outcomes and survival in mice.

P5349Platelet/lymphocyte ratio as an inflammatory marker and predictor of short-term neurological outcomes in survivors after cardiac arrest

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Rodriguez ◽  
L A Martinez ◽  
S O Rosillo ◽  
L Martin ◽  
C Merino ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Paired Comparison ◽  
Inflammatory Marker ◽  
Cerebral Performance Category ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Early Assessment ◽  
Lymphocyte Ratio ◽  
Neurological Outcomes ◽  
The Impact

Abstract Background Platelet/lymphocyte ratio (PLR), an inflammatory marker associated with poor outcomes in different clinical situations, may play a role in the proinflammatory state triggered during hypoxic-ischemic brain injury secondary to cardiac arrest. Purpose To study PLR dynamics and its relationship with neurologic outcomes in survivors after CA treated with target-temperature-management (TTM). Methods Observational retrospective study from a prospective database of survivors of in-hospital and out-of-hospital CA admitted to our Acute Cardiac Care Unit between August 2006 to December 2018. All patients received TTM according to our local protocol. Results A total of 466 patients were included. Mean age was 62.7±14.4 years and 102 (21.9%) were women. Baseline characteristics are shown in Table 1. 430 (92.2%) of CA were witnessed, 312 (67.0%) had ventricular fibrillation as initial cardiac rhythm. Among them, 236 (51.1%) survived until hospital discharge and 208 (45.1%) presented favorable neurological outcomes (a score 1 or 2 on cerebral performance category (CPC)). The mean value of PLR at admission and during targeted temperature was 100.4±5.2 and 224.5±7.3 respectively (mean difference 123.1±7.1, p<0.0001). This increase in PLR was significantly higher among patients with worse neurological outcomes (CPC 3–5, mean DPLR 138.2±5.5) at 3 months compared with survivors with CPC 1–2 (mean DPLR 108.2±6.3, p=0.0348 for paired comparison between both groups). Table 1 Hypertension, n (%) 235 (54.9) Diabetes, n (%) 113 (26.4) Dyslipidaemia, n (%) 171 (40.0) Smocking habit, n (%) 208 (48.5) Time to ROSC mean ± SD, min 26.6±18.6 Mean arterial pressure at HA mean±DS, mmHg 81.3±22.1 pH at HA mean ± SD 7.18±0.16 Lactic at HA mean ± SD 6.37±4.42 ROSC: return of spontaneus circulation; HA: hospital admission. Conclusion Our findings reflect the impact of inflammation in neurological outcomes after OHCA treated with TTM. Major increases of PLR constitute a novel marker of poor prognosis during early assessment of OHCA patients.

Central Nervous System Complications in Cardiac Surgery: Retrograde Cerebral Perfusion, Pressure, Pulsatility, Temperature, and pH Management During Cardiopulmonary Bypass

2000 ◽  
Vol 4 (2) ◽  
pp. 65-69
Author(s):  
John M. Murkin
Keyword(s):  
Circulatory Arrest ◽  
Management Strategies ◽  
Arterial Line ◽  
Neurological Outcomes ◽  
Hypothermic Perfusion ◽  
Management Techniques ◽  
Ph Management ◽  
Pulmonary Bypass ◽  
The Impact ◽  
The Brain

Currently, clinical management strategies during cardio pulmonary bypass (CPB) are undergoing profound changes. Renewed interest in normothermic versus hypothermic perfusion during CPB has resulted in appar ently contradictory results regarding patient outcomes. Much effort has been devoted to defining physiological responses of the brain to various alterations during CPB (eg, pH strategy, normothermia versus hypothermia, pulsatile or nonpulsatile perfusion, use of arterial line filtration, circulatory arrest, retrograde cerebral perfu sion). In addition, prospective studies are examining the impact of diverse strategies on neuropsychological and neurological outcomes after CPB, to define optimal management techniques.

Traumatic Brain Injury: The Silent Epidemic

1992 ◽  
Vol 3 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Kathy Coburn
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
National Database ◽  
Assessment Practices ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Acute Health Care ◽  
Focal Injury ◽  
The Impact ◽  
The Brain

It is difficult to accurately determine the number of people affected annually by the devastating effects of traumatic brain injury. It is clear, however, that the impact of traumatic brain injury exceeds the financial cost of acute health care. The long-term outcome of patients with traumatic brain injury has been targeted specifically for improvement during this decade. The initial brain injury—known as the primary injury—may occur in one area of the brain (focal injury) or may affect the entire brain (diffuse injury). The outcome depends on many factors, including the severity of the brain injury and the effectiveness of the interventions received. Accurate assessment of the scope of the problem would be improved by the development of a national database and the standardization of assessment practices. Critical care nurses can contribute skill and knowledge in the care of patients with traumatic brain injury and in efforts to prevent the accidents and violence that cause traumatic brain injury

111 New Observations in Cerebral Glucose Metabolism Following Traumatic Brain Injury

Neurosurgery ◽  
2015 ◽  
Vol 62 ◽  
pp. 200
Author(s):  
Joshua Robert Dusick ◽  
Thomas C. Glenn ◽  
Paul M. Vespa ◽  
Neil A. Martin
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism
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