Abstract 9180: Importance of Preventing Decreased Levels of Lysophosphatidylcholine—DHA in Brain and Plasma for Attenuating Brain Injury After Cardiac Arrest

Introduction: Lysophosphatidylcholine (LPC) was found to be decreased in plasma in the early phase of resuscitation after cardiac arrest (CA), including a species containing docosahexaenoic acid (LPC-DHA). Supplementing this deficiency of plasma LPC-DHA post-CA significantly attenuated brain dysfunction implicating a causative role of plasma decreased LPC-DHA for brain injury. Previous studies showed the importance of LPC-DHA as a carrier of DHA to maintain proper brain function. However, the role of LPC-DHA for brain function has not been fully understood. Objective: This study is aimed at determining the importance of maintaining proper brain LPC-DHA level via plasma supplementation to prevent brain damage after CA using human patients, animal model, and in-vitro cell studies. Methods and Results: We first evaluated associations between the plasma LPC-DHA levels and neurological outcomes using 45 post-CA patients. We then measured LPC-DHA levels and histological, biochemical, metabolic alterations in the plasma and brain after 10 min CA rat model and examined how these alterations were attenuated by supplementing LPC-DHA. Finally, we further investigated the beneficial effect of LPC-DHA using cell cultures. We found that the decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased level of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized the brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocyte, and expression of various inflammatory and mitochondrial dysfunction genes. We also found normalized overall metabolic alterations from the untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. Conclusion: The attenuation of biochemical and physiologic alterations, and the normalization of decreased brain LPC-DHA post-CA with LPC-DHA supplementation demonstrate plasma LPC-DHA is important for the maintenance of proper brain LPC-DHA levels, which is essential for preventing brain damage post-CA.

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Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Stroke Research and Treatment ◽

10.1155/2013/263974 ◽

2013 ◽

Vol 2013 ◽

pp. 1-42

Author(s):

Jennifer A. Frontera

Keyword(s):

Clinical Trials ◽

Cardiac Arrest ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Randomized Clinical Trials ◽

Early Brain Injury ◽

Aneurysm Rupture ◽

Neurological Outcomes ◽

Injury Research ◽

The Brain

Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH).Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included.Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically.Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

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Neuropsychological Rehabilitation

Examining Biological Foundations of Human Behavior - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-7998-2860-0.ch013 ◽

2020 ◽

pp. 226-242

Author(s):

Geeta Singh ◽

G. S. Kaloiya

Keyword(s):

Brain Injury ◽

Everyday Life ◽

Brain Damage ◽

Cognitive Deficits ◽

Behavioral Deficits ◽

Neuropsychological Rehabilitation ◽

Cognitive Retraining ◽

Life Functioning ◽

The Brain

Neuropsychological rehabilitation is concerned with achievement of maximum potential in diverse domains of psychological, social, vocational, and everyday life functioning in people with cognitive, emotional, psychosocial, and behavioral deficits caused by an insult to the brain. Hence, neuropsychological rehabilitation is the process of helping a patient to recover the functions that are impaired due to brain injury. The major role of neuropsychological rehabilitation is the improvement of cognitive deficits resulting from brain damage using extensive cognitive retraining. This chapter explores neuropsychological rehabilitation.

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Real-Time Brain Monitoring by Near-Infrared Spectroscopy Predicts Neurological Outcome after Cardiac Arrest and Resuscitation in Rats: A Proof of Concept Study of a Novel Prognostic Measure after Cardiac Arrest

Journal of Clinical Medicine ◽

10.3390/jcm11010131 ◽

2021 ◽

Vol 11 (1) ◽

pp. 131

Author(s):

Ryosuke Takegawa ◽

Kei Hayashida ◽

Tai Yin ◽

Rishabh C. Choudhary ◽

Santiago J. Miyara ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Near Infrared ◽

Mitochondrial Fission ◽

Spontaneous Circulation ◽

Gene Expressions ◽

Dynamic Changes ◽

Neurological Outcomes ◽

Fluoro Jade B ◽

The Brain

Clinical studies have demonstrated that dynamic changes in regional cerebral oxygen saturation (rSO2) after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) have a role in predicting neurological outcomes after the return of spontaneous circulation (ROSC). Our study evaluated whether the timing of rSO2 decline shortly after CPR reflects the severity of brain injury in a rat model of CA. Rats were subjected to different durations of asphyxia to produce variable severities of brain injury, due to CA. Time from ROSC to achieving the initial minimum rSO2 was defined as Tnadir. A Tnadir cut-off of 24 min had optimal sensitivity and specificity for predicting good neurological outcomes at 72 h after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; p < 0.01). Immunohistochemistry at 72 h post-CA revealed that the number of Fluoro-Jade B positive degenerating neurons in the hippocampus CA1 sector were markedly higher in animals with Tnadir > 24 min than that in animals with Tnadir ≤ 24 min. There was no difference in the gene expressions of cytokines and mitochondrial fission proteins in the brain at 2 h after ROSC between rats with Tnadir > 24 min and with Tnadir ≤ 24 min. In conclusion, Tnadir can be a novel predictor of good neurological outcomes after CA/CPR.

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Abstract 122: The Role of Plasma Lysophosphatidylcholine in Patients With Out-of-Hospital Cardiac Arrest

Circulation ◽

10.1161/circ.138.suppl_2.122 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Tsukasa Yagi ◽

Tai Yin ◽

Koichiro Shinozaki ◽

Lance B Becker ◽

Junhwan Kim

Keyword(s):

Fatty Acids ◽

Cardiac Arrest ◽

Brain Damage ◽

Brain Function ◽

Saturated Fatty Acids ◽

Acyl Chain ◽

University Hospital ◽

Proper Function ◽

The Brain ◽

Hospital Cardiac Arrest

Background: Phosphatidylcholine (PC) is the most abundant class of phospholipid found in plasma. Lysophosphatidylcholine (LPC), PC missing one acyl chain, is believed to be the main carrier of polyunsaturated fatty acids (PUFAs) to the brain. The continuous supply of PUFAs, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), are important to maintain proper function of the brain. Therefore, alterations in the plasma levels of LPC containing these fatty acids, LPC-EPA, LPC-DHA, and LPC-AA, indicate impaired delivery of fatty acids, which in turn may indicate abnormal brain function. Numerous animal studies have found altered LPC compositions in Alzheimer’s disease, cognitive impairment, brain ischemia, and aging. Moreover, administration of LPC has been shown to improve brain function in these pathological conditions. Since brain damage is the main cause of death in cardiac arrest, altered LPC profiles may be indicative of brain damage and also play a role in the recovery of brain function. The aim of this study was to measure the content of plasma LPC species in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. Methods: Blood samples were obtained from 11 OHCA patients, who were admitted to Northshore University Hospital and achieved return of spontaneous circulation. Within 4 h of drawing, plasma was separated from the whole blood using centrifugation and stored at -80°C. Control samples were obtained from 19 healthy volunteers. The contents of LPC species were measured using LC-mass spectrometry. Results: We found the overall content of LPC is significantly lower in OHCA patients. The decrease is found in all species of LPC, including LPC-EPA (patients vs Controls = 0.17 vs 0.55 μmol/L, p=0.003), LPC-DHA (patients vs Controls = 0.47 vs 1.72 μmol/L, p=0.003), and LPC-AA (patients vs Controls = 1.98 vs 5.39 μmol/L, p<0.001). We also found decreased in LPC species containing saturated fatty acids, showing the decrease was not specific to PUFAs. Conclusion: We found OHCA patients have a significantly lower plasma LPC content. Understanding the detailed mechanism for this decrease and the role that LPC plays in the recovery of patients after OHCA requires more investigation.

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Creatine Supplementation and Brain Health

Nutrients ◽

10.3390/nu13020586 ◽

2021 ◽

Vol 13 (2) ◽

pp. 586 ◽

Cited By ~ 2

Author(s):

Hamilton Roschel ◽

Bruno Gualano ◽

Sergej M. Ostojic ◽

Eric S. Rawson

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Cognitive Function ◽

Cognitive Processing ◽

Brain Function ◽

Creatine Supplementation ◽

Short Review ◽

Future Research ◽

Brain Health

There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (e.g., cognitive processing, brain function, and recovery from trauma). This is a growing field of research, and the purpose of this short review is to provide an update on the effects of creatine supplementation on brain health in humans. There is a potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by brain creatine deficits, which could be induced by acute stressors (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression). Despite this, the optimal creatine protocol able to increase brain creatine levels is still to be determined. Similarly, supplementation studies concomitantly assessing brain creatine and cognitive function are needed. Collectively, data available are promising and future research in the area is warranted.

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ChemInform Abstract: Role of Heart-Type Fatty Acid Binding Protein in the Brain Function

ChemInform ◽

10.1002/chin.200926278 ◽

2009 ◽

Vol 40 (26) ◽

Author(s):

Keiju Motohashi ◽

Yui Yamamoto ◽

Norifumi Shioda ◽

Hisatake Kondo ◽

Yuji Owada ◽

...

Keyword(s):

Fatty Acid ◽

Brain Function ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

The Brain

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Abstract 273: Noninvasive Mitochondrial Modulation: Neuroprotection in a Translational Model of Cardiac Arrest and Resuscitation

Circulation ◽

10.1161/circ.140.suppl_2.273 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Joseph M Wider ◽

Erin Gruley ◽

Jennifer Mathieu ◽

Emma Murphy ◽

Rachel Mount ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Near Infrared ◽

Small Animal ◽

Spontaneous Circulation ◽

Infrared Light ◽

Swine Model ◽

Treatment Groups ◽

The Brain ◽

Neuroprotective Therapies

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.

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Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

Current Medicinal Chemistry ◽

10.2174/0929867328666210923143713 ◽

2021 ◽

Vol 28 ◽

Author(s):

Lucas Alexandre Santos Marzano ◽

Fabyolla Lúcia Macedo de Castro ◽

Caroline Amaral Machado ◽

João Luís Vieira Monteiro de Barros ◽

Thiago Macedo e Cordeiro ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Clinical Studies ◽

Molecular Mechanisms ◽

Hippocampal Neurogenesis ◽

Cognitive Outcomes ◽

Adult Hippocampal Neurogenesis ◽

The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

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The concentration of ascorbic acid in the cerebral cortex and internal organs of rats in chronic and acute hyperglycemia

Problems of Endocrinology ◽

10.14341/probl199844140-42 ◽

1998 ◽

Vol 44 (1) ◽

pp. 40-42

Author(s):

I. P. Grigoriev

Keyword(s):

Ascorbic Acid ◽

Brain Cortex ◽

Mental Disease ◽

Streptozotocin Diabetes ◽

Causative Role ◽

Internal Organs ◽

Acute Hyperglycemia ◽

Acute Hypoglycemia ◽

The Brain

The author hypothesizes a probable causative role of alteration of ascorbic acid concentration in the brain in the development of mental disease in diabetics. In order to verify this hypothesis, ascorbic acid was measured in the brain cortex of rats 21 days after induction of streptozotocin diabetes or 1 h after intraperitoneal injection of glucose in a dose of 5 g/kg. Ascorbic acid level was increased both in diabetes (456+26 yg/g tissue versus 415+37 \vg/g in the control, p<0.01) and in acute hyperglycemia (475+54 \tg/g versus 406+65 \xg/g in the control, p<0.001). This confirmed that changed concentration of ascorbic acid in the brain can promote the development of a mental disease in diabetics. In the liver the concentration of ascorbic acid was decreased in streptozotocin diabetes (by 17%), p<0.001) and increased in acute hypoglycemia (by 24%, p<0.01). The findings permit us to hypothesize that hypoglycemia inhibits the production of ascorbic acid from the liver to the blood in rats and impedes the transport of ascorbic acid through the gut wall into the blood in humans.

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Neurogenesis and Oligodendrogenesis in a Mouse Model of Blast-Induced Traumatic Brain Injury

Neurology and Neurobiology ◽

10.31487/j.nnb.2020.03.07 ◽

2020 ◽

pp. 1-14

Author(s):

Michal K. Stachowiak ◽

D. Freedman ◽

N. Nived ◽

B. Decker ◽

S. Narla ◽

...

Keyword(s):

Brain Injury ◽

Brain Function ◽

Brain Cortex ◽

Post Traumatic Stress ◽

Model Following ◽

Initial Injury ◽

Initial Activation ◽

Post Traumatic ◽

Oligodendrocyte Precursor ◽

The Brain

Neurological manifestations of blast-induced Post Traumatic Stress Disorder (PTSD) extend long after the initial injury indicating lasting changes in brain function. In this study, we characterized brain injury, changes in neurogenesis and oligodendrogenesis in an adult murine blast model following a short (5 days) and long (21 days) post-blast recovery. Acoustic blasts led to an initial, activation of microglia and astrogliosis and a widespread cortical and subcortical apoptosis. The loss of myelinated cortical axons at 5 days was followed by the reappearance of abnormal misdirected fibers at 21 days. At 21 days post-blast, we observed increases in doublecortin-positive (DCX+ ) neuroblasts in the subventricular zone (SVZ) and hippocampal subgranular zone (SGZ) indicating increased neurogenesis. No changes in DCX+ cells were found in the brain cortex. In the cortex, the early disappearance of myelinated neuronal fibers was accompanied by a loss of O4+ oligodendrocytes and their Ki67-expreasing (Ki67+ ) oligodendrocyte precursor cells (OPC). However, at 5 days we observed a robust appearance of cells expressing Olig2 (O2+ ), an early determinant of oligodendrocyte lineage. At 21 days post-blast, the population of OPC increased and the mature O4+ oligodendrocytes were restored to control levels. In contrast, in the SVZ and SGZ, O4+ cells were not affected by the blast suggesting a local cortical origin for cortical oligodendrogenesis. These results suggest that blast-induced activation of SVZ and SGZ neurogenesis and cortical oligodendrogenesis could have long-lasting impact on brain function including memory disorders observed in both animal models and human’s PTSD.

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