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Brain disease

Isabella Zhang, Silvia C Formenti, Jonathan P S Knisely
The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies...
March 15, 2018: Oncology (Williston Park, NY)
Vassilis E Papadopoulos, Georgia Nikolopoulou, Ivi Antoniadou, Antonia Karachaliou, Giovanna Arianoglou, Evangelia Emmanouilidou, S Pablo Sardi, Leonidas Stefanis, Kostas Vekrellis
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's Disease (PD) and are associated with decreased Glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system (CNS) suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein, a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes...
March 14, 2018: Human Molecular Genetics
Michael Baer, Bradley Klemetson, Diana Scott, Andrew S Murtishaw, James W Navalta, Jefferson W Kinney, Merrill R Landers
BACKGROUND AND PURPOSE: Because falls can have deleterious consequences, it is important to understand the influence of fatigue and medications on balance in persons with Parkinson disease (PD). Thus, the purpose of this study was to investigate the effects of fatigue on balance in individuals with PD. Because brain-derived neurotrophic factor (BDNF) has been shown to be related to motor performance, we also explored its role. METHODS: A total of 27 individuals (age = 65...
April 2018: Journal of Neurologic Physical Therapy: JNPT
Tsinsue Chen, Zaman Mirzadeh, Kristina M Chapple, Margaret Lambert, Holly A Shill, Guillermo Moguel-Cobos, Alexander I Tröster, Rohit Dhall, Francisco A Ponce
OBJECTIVE Recent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called "asleep" DBS, and historical cohorts undergoing "awake" DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution...
March 16, 2018: Journal of Neurosurgery
Takuma Ohmichi, Masaki Kondo, Masahiro Itsukage, Hidetaka Koizumi, Shigenori Matsushima, Nagato Kuriyama, Kazunari Ishii, Etsuro Mori, Kei Yamada, Toshiki Mizuno, Takahiko Tokuda
OBJECTIVE The gold standard for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is the CSF removal test. For elderly patients, however, a less invasive diagnostic method is required. On MRI, high-convexity tightness was reported to be an important finding for the diagnosis of iNPH. On SPECT, patients with iNPH often show hyperperfusion of the high-convexity area. The authors tested 2 hypotheses regarding the SPECT finding: 1) it is relative hyperperfusion reflecting the increased gray matter density of the convexity, and 2) it is useful for the diagnosis of iNPH...
March 16, 2018: Journal of Neurosurgery
Mari Miyata, Shingo Kakeda, Kohsuke Kudo, Shigeru Iwata, Yoshiya Tanaka, Yi Wang, Yukunori Korogi
The purposes of this study are to assess the oxygen extraction fraction (OEF) changes on MRI-based quantitative susceptibility mapping (QSM) in systemic lupus erythematosus (SLE) patients and to determine whether QSM-OEF is associated with disease activity in SLE. We enrolled 42 SLE patients and 20 healthy subjects (HS) who had no pathologies on conventional brain MRI. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). For the measurement of QSM-OEF, QSM data were analysed using the Perfusion Mismatch Analyzer software program...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Chih-Wei Hsu, Chin-Chuen Lin, Tiao-Lai Huang
No abstract text is available yet for this article.
March 2018: Psychiatria Danubina
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Inbal Maidan, Freek Nieuwhof, Hagar Bernad-Elazari, Bastiaan R Bloem, Nir Giladi, Jeffrey M Hausdorff, Jurgen A H R Claassen, Anat Mirelman
BACKGROUND: In a randomized control trial conducted in patients with Parkinson's disease, a treadmill training program combined with virtual reality that targeted motor and cognitive aspects of safe ambulation led to fewer falls, compared with treadmill training alone. OBJECTIVE: To investigate if the 2 types of training differentially affected prefrontal activation and if this might explain differences in fall rates after the intervention. METHODS: Sixty-four patients with Parkinson's disease were randomized into the treadmill training arm (n = 34, mean age 73...
March 1, 2018: Neurorehabilitation and Neural Repair
Anna King, Anna Brain, Kelsey Hanson, Justin Dittmann, James Vickers, Carmen Fernandez-Martos
Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice...
March 15, 2018: Metabolic Brain Disease
Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan Lundberg
Major depressive disorder (MDD) is the leading cause of disability worldwide. The serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory receptors such as the serotonin 1B receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the receptor...
March 15, 2018: Psychopharmacology
Matheus D Baldissera, Carine F Souza, Carla Cristina Zeppenfeld, Sharine Descovi, Aleksandro S da Silva, Bernardo Baldisserotto
The phosphotransfer network system, through the enzymes creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), contributes to efficient intracellular energetic communication between cellular adenosine triphosphate (ATP) consumption and production in tissues with high energetic demand, such as cerebral tissue. Thus, the aim of this study was to evaluate whether aflatoxin B1 (AFB1 ) intoxication in diet negatively affects the cerebral phosphotransfer network related to impairment of cerebral ATP levels in silver catfish (Rhamdia quelen)...
March 15, 2018: Fish Physiology and Biochemistry
Brent D Weinberg, Lauren Boreta, Steve Braunstein, Soonmee Cha
Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement...
March 15, 2018: Journal of Neuro-oncology
Jose M Sanchez Bornot, KongFatt Wong-Lin, Alwani Liyana Ahmad, Girijesh Prasad
The brain's functional connectivity (FC) estimated at sensor level from electromagnetic (EEG/MEG) signals can provide quick and useful information towards understanding cognition and brain disorders. Volume conduction (VC) is a fundamental issue in FC analysis due to the effects of instantaneous correlations. FC methods based on the imaginary part of the coherence (iCOH) of any two signals are readily robust to VC effects, but neglecting the real part of the coherence leads to negligible FC when the processes are truly connected but with zero or π-phase (modulus 2π) interaction...
March 15, 2018: Brain Topography
Cyndya A Shibao, Jorge E Celedonio, Robyn Tamboli, Reem Sidani, Latisha Love-Gregory, Terri Pietka, Yanhua Xiong, Yan Wei, Naji N Abumrad, Nada A Abumrad, Charles Robb Flynn
Context: Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism but whether it has similar actions in humans is unknown. We examined impact of a coding single-nucleotide polymorphism in CD36 on post-prandial hormone and bile acid (BA) responses. Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences hormonal responses to a high-fat meal (HFM)...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Qin Rui, Haibo Ni, Fan Gao, Baoqi Dang, Di Li, Rong Gao, Gang Chen
Leucine-rich repeat kinase 2 (LRRK2) is widely expressed in the brain and exerts neurotoxicity in Parkinson's disease. The p38/Drosha signaling activation has been reported to increase cell death under stress. This study was designed to investigate the potential role and mechanism of LRRK2 in secondary brain injury after traumatic brain injury (TBI). A total of 130 male Sprague-Dawley rats were examined using a weight-drop model of TBI. The rats received the specific LRRK2 inhibitor PF-06447475 or LRRK2 pDNA alone or in combination with Drosha pDNA...
2018: Frontiers in Cellular Neuroscience
Misato Yoshikawa, Yoshiyuki Soeda, Makoto Michikawa, Osborne F X Almeida, Akihiko Takashima
Hippocampal hyperactivity, ascribed to amyloid β (Aβ)-induced imbalances in neural excitation and inhibition, is found in patients with mild cognitive impairment, a prodromal stage of Alzheimer's disease (AD). To better understand the relationship between hippocampal hyperactivity and the molecular triggers of behavioral impairments in AD, we used Mn-enhanced MRI (MEMRI) to assess neuronal activity after subjecting mice to a task requiring spatial learning and memory. Depletion of endogenous tau in an amyloid precursor protein (APP) transgenic (J20) mouse line was shown to ameliorate hippocampal hyperactivity in J20 animals, tau depletion failed to reverse memory deficits associated with APP/Aβ overproduction...
2018: Frontiers in Neuroscience
Luis R Peraza, Ruth Cromarty, Xenia Kobeleva, Michael J Firbank, Alison Killen, Sara Graziadio, Alan J Thomas, John T O'Brien, John-Paul Taylor
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias...
March 15, 2018: Scientific Reports
Xueying Wang, Ksenia V Kastanenka, Michal Arbel-Ornath, Caitlin Commins, Akira Kuzuya, Amanda J Lariviere, Grant A Krafft, Franz Hefti, Jasna Jerecic, Brian J Bacskai
Soluble amyloid β oligomers (AβOs) are widely recognized neurotoxins that trigger aberrant signaling in specific subsets of neurons, leading to accumulated neuronal damage and memory disorders in Alzheimer's disease (AD). One of the profound downstream consequences of AβO-triggered events is dysregulation of cytosolic calcium concentration ([Ca2+ ]i ), which has been implicated in synaptic failure, cytoskeletal abnormalities, and eventually neuronal death. We have developed an in vitro/in vivo drug screening assay to evaluate putative AβO-blocking candidates by measuring AβO-induced real-time changes in [Ca2+ ]i ...
March 15, 2018: Scientific Reports
Marc P Forrest, Euan Parnell, Peter Penzes
The structure of neuronal circuits that subserve cognitive functions in the brain is shaped and refined throughout development and into adulthood. Evidence from human and animal studies suggests that the cellular and synaptic substrates of these circuits are atypical in neuropsychiatric disorders, indicating that altered structural plasticity may be an important part of the disease biology. Advances in genetics have redefined our understanding of neuropsychiatric disorders and have revealed a spectrum of risk factors that impact pathways known to influence structural plasticity...
March 16, 2018: Nature Reviews. Neuroscience
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