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Brain death

Maria Shoaib, Jacqueline J Kraus, Muhammad T Khan
Herpes simplex virus encephalitis (HSVE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis. We report a case of HSVE presenting as a stroke mimic in a 76-year-old female with a history of atrial fibrillation on warfarin. She was admitted to our medical intensive care unit with intermittent fever, lethargy, and new onset left-sided hemiparesis...
January 15, 2018: Curēus
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
Jin Wu, Todd Vogel, Xiang Gao, Bin Lin, Charles Kulwin, Jinhui Chen
No FDA approved pharmacological therapy is available that would reduce cell death following traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective agonist of alpha-2 adrenergic receptors and has demonstrated neuroprotective effects in hippocampal slice cultures undergoing direct impact. However, no one has tested whether Dex, in addition to its sedative action, has neuroprotective effects in an animal model of TBI. Thus, in the present study, we investigated the effects of Dex on an animal model of TBI...
March 21, 2018: Scientific Reports
Marianne S Joerger-Messerli, Byron Oppliger, Marialuigia Spinelli, Gierin Thomi, Ivana di Salvo, Philipp Schneider, Andreina Schoeberlein
Hypoxic-ischemic (HI) insult in the perinatal phase harbors a high risk of encephalopathy in the neonate. Brain cells undergo apoptosis, initiating neurodegeneration. So far, therapeutic approaches such as cooling remain limited. Transplantation of mesenchymal stem cells (MSCs) exhibits therapeutic success despite the short-time survival in the host brain, providing strong evidence that their beneficial effects are largely based on secreted factors, including extracellular vesicles (EVs). The aim of this study was to investigate the effects of human Wharton's jelly MSC (hWJ-MSC)-derived EVs on neuroprotection and neuroregeneration, using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) mimicking HI injury in the mouse neuroblastoma cell line neuro2a (N2a)...
January 2018: Cell Transplantation
Ewelina Bratek, Apolonia Ziembowicz, Elzbieta Salinska
Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear...
March 17, 2018: Brain Sciences
D Allan Butterfield, Debra Boyd-Kimball
Oxidative stress is implicated in the pathogenesis and progression of Alzheimer's disease (AD) and its earlier stage, amnestic mild cognitive impairment (aMCI). One source of oxidative stress in AD and aMCI brains is that associated with amyloid-β peptide, Aβ1-42 oligomers. Our laboratory first showed in AD elevated oxidative stress occurred in brain regions rich in Aβ1-42, but not in Aβ1-42-poor regions, and was among the first to demonstrate Aβ peptides led to lipid peroxidation (indexed by HNE) in AD and aMCI brains...
2018: Journal of Alzheimer's Disease: JAD
Patrizia Mecocci, Marta Baroni, Umberto Senin, Virginia Boccardi
Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Faissal Stipho, Robert Jackson, Marwan N Sabbagh
BACKGROUND: Homozygous APOEɛ4 status is a well-known risk factor in the development of Alzheimer's disease (AD). However, other genotypes of APOE have not yet been found to have equal clinical significance. There is a paucity of reports regarding clinically or pathologically described AD in APOEɛ2 homozygotes compared to the other alleles. OBJECTIVE: To notify clinicians that patients with homozygous APOEɛ2 are also at risk of developing AD based on results from the largest prospectively gathered registry of brain samples to date...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Walderik W Zomerman, Sabine L A Plasschaert, Siobhan Conroy, Frank J Scherpen, Tiny G J Meeuwsen-de Boer, Harm J Lourens, Sergi Guerrero Llobet, Marlinde J Smit, Lorian Slagter-Menkema, Annika Seitz, Corrie E M Gidding, Esther Hulleman, Pieter Wesseling, Lisethe Meijer, Leon C van Kempen, Anke van den Berg, Daniël O Warmerdam, Frank A E Kruyt, Floris Foijer, Marcel A T M van Vugt, Wilfred F A den Dunnen, Eelco W Hoving, Victor Guryev, Eveline S J M de Bont, Sophia W M Bruggeman
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling...
March 20, 2018: Cell Reports
Selene Pozzebon, Aaron Blandino Ortiz, Federico Franchi, Stefano Cristallini, Mirko Belliato, Olivier Lheureux, Alexandre Brasseur, Jean-Louis Vincent, Sabino Scolletta, Jacques Creteur, Fabio Silvio Taccone
BACKGROUND: Acute cerebral complications (ACC) of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are associated with poor long-term neurologic outcome. We described the role of rSO2 monitoring in detecting ACC and desaturations and their relationship with poor outcome when employing VA-ECMO. METHODS: Retrospective analysis of patients monitored by cerebral frontal near-infrared spectroscopy (NIRS) (CAS Medical Systems Inc., Branford, CT, USA) during VA-ECMO (November 2008-December 2015)...
March 20, 2018: Neurocritical Care
E David Bell, Matthew Converse, Haojie Mao, Ginu Unnikrishnan, Jaques Reifman, Kenneth L Monson
Traumatic brain injury (TBI), resulting from either impact- or non-impact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries...
March 19, 2018: Journal of Biomechanical Engineering
Mads N Olesen, Josefine R Christiansen, Steen Vang Petersen, Poul Henning Jensen, Wojciech Paslawski, Marina Romero-Ramos, Vanesa Sanchez-Guajardo
We have previously shown that immunological processes in the brain during α-synuclein-induced neurodegeneration vary depending on the presence or absence of cell death. This suggests that the immune system is able to react differently to the different stages of α-synuclein pathology. However, it was unclear whether these immune changes were governed by brain processes or by a direct immune response to α-synuclein modifications. We have herein locally increased the peripheral concentration of α-synuclein or its pathology-associated variants, nitrated or fibrillar, to characterize the modulation of the CD4 T cell pool by α-synuclein and brain microglia in the absence of any α-synuclein brain pathology...
January 2018: Heliyon
Daniel G Miller, Priyanka Vakkalanka, Mark L Moubarek, Sangil Lee, Nicholas M Mohr
Introduction: This study investigated whether a 9.6% decrease in the use of head computed tomography (HCT) for patients presenting to the emergency department (ED) with a chief complaint of headache was followed by an increase in proportions of death or missed intracranial diagnosis during the 22.5-month period following each index ED visit. Methods: We reviewed the electronic medical records of all patients sampled during a quality improvement effort in which the aforementioned decrease in HCT use had been observed...
March 2018: Western Journal of Emergency Medicine
Anjan Debnath, Andrew T Nelson, Angélica Silva-Olivares, Mineko Shibayama, Dionicio Siegel, James H McKerrow
Primary amebic meningoencephalitis (PAM) is a fatal infection caused by the free-living ameba Naegleria fowleri , popularly known as the "brain-eating ameba." The drugs of choice in treating PAM are the antifungal amphotericin B and an antileishmanial miltefosine, but these are not FDA-approved for this indication and use of amphotericin B is associated with severe adverse effects. Moreover, very few patients treated with the combination therapy have survived PAM. Therefore, development of efficient drugs is a critical unmet need to avert future deaths of children...
2018: Frontiers in Microbiology
Thanh G Phan, Jian Chen, Shaloo Singhal, Henry Ma, Benjamin B Clissold, John Ly, Richard Beare
Background: Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. Method: The inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003-2011)...
2018: Frontiers in Neurology
Amish Chinoy, Indraneel Banerjee, Sarah E Flanagan, Sian Ellard, Bing Han, Zainab Mohamed, Mark J Dunne, Stefania Bitetti
Congenital hyperinsulinism (CHI) is the commonest cause of persistent and severe hypoglycemia in infancy due to unregulated insulin secretion from pancreatic β-cells. Prompt early diagnosis is important, as insulin reduces glucose supply to the brain, resulting in significant brain injury and risk of death. Histologically, CHI has focal and diffuse forms; in focal CHI, an inappropriate level of insulin is secreted from localized β-cell hyperplasia. We report a 4-month-old male infant, who presented with sudden illness and collapse without a recognized cause and died...
January 1, 2018: Pediatric and Developmental Pathology
Candy S Hwang, Lauren C Smith, Yoshihiro Natori, Beverly Ellis, Bin Zhou, Kim D Janda
The sharp increase in overdose deaths involving illicit opioid use has been declared a national crisis in the United States. This growing number of overdose deaths can in part be attributed to the increased frequency of fentanyl contamination in the United States heroin supply. To combat this growing trend, we designed a vaccine containing a mixture of heroin and fentanyl hapten-conjugates as a proof-of-concept immunotherapy targeting a combination of these drugs. Rodents immunized with the admixture vaccine showed drug retention in serum and reduced distribution in the brain after administration of an intravenous bolus of heroin coadministered with fentanyl (10% w/w)...
March 23, 2018: ACS Chemical Neuroscience
Hyun Goo Kang, Bum Joon Kim, Sang Hun Lee, Dong-Wha Kang, Sun U Kwon, Jong S Kim
BACKGROUND: Lateral medullary infarction (LMI) is not an uncommon disease. Although lesions are usually restricted to the lateral medullary area, some patients have additional infarcts in other parts of the brain. The clinical features and prognosis of isolated LMI (pure LMI, LMIpr) have been investigated. However, it remains unclear whether clinical characteristics, prognosis and factors associated with prognosis differ between patients with LMIpr and those with additional lesions (LMI plus, LMIpl)...
March 20, 2018: Cerebrovascular Diseases
Michelle Hershman, Raymond Carmody, Unni K Udayasankar
History A 19-year-old woman with no pertinent medical history was brought to the emergency department after being found unconscious on her bathroom floor by her roommate. In the preceding weeks, she had reported intractable nausea and vomiting, for which she had been taking ondansetron. No other medications had been prescribed. The day prior to presentation, she had contacted her mother and described increasing confusion. Glasgow coma scale score on arrival in the emergency department was 4. Intravenous naloxone was administered, without immediate response...
April 2018: Radiology
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
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