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brain chemistry

Matthew G Stovell, Marius O Mada, Adel Helmy, T Adrian Carpenter, Eric P Thelin, Jiun-Lin Yan, Mathew R Guilfoyle, Ibrahim Jalloh, Duncan J Howe, Peter Grice, Andrew Mason, Susan Giorgi-Coll, Clare N Gallagher, Michael P Murphy, David K Menon, Peter J Hutchinson, Keri L H Carpenter
A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with 31 P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days)...
July 24, 2018: Scientific Reports
Niels Hadrup, Katrin Loeschner, Karen Mandrup, Gitte Ravn-Haren, Henrik L Frandsen, Erik H Larsen, Henrik R Lam, Alicja Mortensen
Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28 d with either: 0.05, 0.5, or 4 mg Se/kg body weight (bw)/day as 20 nm Se nanoparticles or 0.05 or 0.5 mg Se/kg bw/day as sodium selenite. Male rats were dosed 4 mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment...
July 23, 2018: Drug and Chemical Toxicology
A West, J Best, A Abdalla, F Nijhout, M Reed, P Hashemi
The medial prefrontal cortex (mPFC) is an important brain region, that controls a variety of behavioral and functional outputs. As an important step in characterizing mPFC functionality, In this paper we focus on chemically defining serotonin transmission in this area. We apply cutting-edge analytical methods, fast-scan cyclic voltammetry (FSCV) and fast-scan controlled adsorption cyclic voltammetry (FSCAV), pioneered in our laboratory, for the first real-time in vivo analysis of serotonin in the mPFC. In prior in vivo work in the substantia nigra, pars reticulata, we found that our sub-second measurements of a single evoked serotonin release were subject to two clearance mechanisms...
July 18, 2018: Neurochemistry International
Lina Begdache, Hamed Kianmehr, Nasim Sabounchi, Maher Chaar, Jade Marhaba
Independent reports describe the structural differences between the human male and female brains and the differential gender-susceptibility to mood disorders. Nutrition is one of the modifiable risk factors that has been reported to impact brain chemistry and affect mental health. OBJECTIVES: To study dietary patterns in adult men and women in relation to mental distress. Another aim was to develop evidence-based prototypes using System Dynamic Modeling methodology to better describe our findings...
July 20, 2018: Nutritional Neuroscience
Harvey S Chen, Dong Jin Joo, Mohammed Shaheen, Yi Li, Yujia Wang, Jian Yang, Clara T Nicolas, Kelly Predmore, Bruce Amiot, Gregory Michalak, Taofic Mounajjed, Jeff Fidler, Walter K Kremers, Scott L Nyberg
BACKGROUND: Acute Liver Failure (ALF) is a catastrophic condition that can occur after major liver resection. The aim of this study was to determine the effects of the spheroid reservoir bio-artificial liver (SRBAL) on survival, serum chemistry and liver regeneration in post-hepatectomy ALF pigs. METHODS: Wild-type large white swine (20-30kg) underwent ICP probe placement followed by 85% hepatectomy. CT volumetrics were performed to measure the extent of resection, and at 48 hours post-hepatectomy to assess regeneration of the remnant liver...
July 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mohammad K Ashfaq, Mohamed Sadek Abdel-Bakky, Mir Tahir Maqbool, Volodymyr Samoylenko, Aziz Abdur Rahman, Ilias Muhammad
In this study, 2,3-dihydro-1 H -indolizinium alkaloid-prosopilosidine (PPD), that was isolated from Prosopis glandulosa , was evaluated against C. neoformans in a murine model of cryptococcosis. In vitro and in vivo toxicity of indolizidines were also evaluated. Mice were infected via the tail vein with live C. neoformans . Twenty-four hours post-infection, the mice were treated with PPD once a day (i.p.) or twice a day ( bid ) orally, or with amphotericin B (Amp B) intraperitoneally (IP), or with fluconazole (Flu) orally for 5 days...
July 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Anke H Scultetus, Michelle A Jefferson, Ashraful Haque, Lam Thuy Vi Tran Ho, Brittany Hazzard, Biswajit K Saha, Steve J Chun, Charles R Auker, Paula F Moon-Massat, Richard M McCarron, Debra L Malone
BACKGROUND: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria on either the flight crew or patients. The effects of hypobaria was investigated using healthy swine. METHODS: Anesthetized Yorkshire swine underwent a simulated 4 h "transport" to an altitude of 2,441 m (8,000 ft.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiological and biochemical data were collected...
July 5, 2018: Journal of Trauma and Acute Care Surgery
Scott P Fletcher, Asif Noor, James L Hickey, Catriona A McLean, Jonathan M White, Paul S Donnelly
Age-associated deposition of amyloid-β in cerebral blood vessels, a condition referred to as cerebral amyloid angiopathy, can contribute to stroke and dementia. This research aimed to design new radioactive technetium-99 m complexes that bind to amyloid-β plaques that have the potential to assist in diagnosis of cerebral amyloid angiopathy using single-photon-emitted computed tomography (SPECT) imaging. Six new pyridylthiosemicarbazide ligands containing either benzofuran or styrylpyridyl functional groups that are known to selectively bind to amyloid plaques were prepared...
July 7, 2018: Journal of Biological Inorganic Chemistry: JBIC
Gang Jia, Yong Han, Yanli An, Yinan Ding, Chen He, Xihui Wang, Qiusha Tang
Currently, glioma treatment is limited by two main factors: timely detection at onset or relapse and restriction of drugs by the blood-brain barrier (BBB) from entering the brain and influencing tumor growth. However, a safe BBB-traversing drug delivery system has brought new hope to glioma treatment. Exosomes have strong cargo-loading capacity and have the ability to cross the BBB. They can also be conferred with the ability for targeted delivery. Therefore, exosomes have great promise to be a targeted drug delivery vehicles...
September 2018: Biomaterials
Qiaozhu Tan, Zhitao Liu, Hong Li, Yongjun Liu, Zhenghua Xia, Yuancan Xiao, Muhammad Usman, Yuzhi Du, Hongtao Bi, Lixin Wei
Mercury chloride (HgCl2 ), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2 , mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1β and inhibited cell proliferation...
July 5, 2018: Toxicology
Jeroen G H P Verhoeven, Karin Boer, Ron H N Van Schaik, Olivier C Manintveld, Manon M H Huibers, Carla C Baan, Dennis A Hesselink
Despite modern immunosuppressive therapy, allograft rejection remains a major cause of solid organ transplant (SOT) dysfunction. For clinical care, organ transplant function is routinely monitored by measuring biomarkers that, depending on the organ transplanted, include serum creatinine, N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) and aspartate aminotransferase (ASAT). All can be measured easily in clinical chemistry laboratories. The main problem with these biomarkers is that they have a low sensitivity for the detection of allograft damage and are non-specific for the detection of allograft rejection...
June 26, 2018: Therapeutic Drug Monitoring
Md Mostafijur Rahman, Md Bayejid Hosen, M Zakir Hossain Howlader, Yearul Kabir
BACKGROUND: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease,and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. METHODS: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method...
June 29, 2018: Current Computer-aided Drug Design
Maria A De Luca, Matthew W Buczynski, Gaetano Di Chiara
Loren (Larry) H. Parsons passed away at the age of 51. In spite of his premature departure, Larry much contributed to the drug abuse field. Since his graduate studies for the Ph.D. in Chemistry in J.B. Justice lab, microdialysis is the tread that links Larry's research topics, namely, the role of dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate and endocannabinoids (eCBs) in drug reinforcement and dependence. Larry was the first to show that abstinence from chronic cocaine reduces extracellular DA in the NAc, consistent with the so called 'dopamine depletion hypothesis' of cocaine addiction...
June 27, 2018: Addiction Biology
Xiao Wang, William E Allen, Matthew A Wright, Emily L Sylwestrak, Nikolay Samusik, Sam Vesuna, Kathryn Evans, Cindy Liu, Charu Ramakrishnan, Jia Liu, Garry P Nolan, Felice-Alessio Bava, Karl Deisseroth
Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility...
July 27, 2018: Science
Decai Tian, Xiaodong Zhu, Rong Xue, Peng Zhao, Yuanrong Yao
History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function...
July 2018: Radiology
Walter Koroshetz, Joshua Gordon, Amy Adams, Andrea Beckel-Mitchener, James Churchill, Gregory Farber, Michelle Freund, Jim Gnadt, Nina S Hsu, Nicholas Langhals, Sarah Lisanby, Guoying Liu, Grace C Y Peng, Khara Ramos, Michael Steinmetz, Edmund Talley, Samantha White
The BRAIN Initiative arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system (CNS). As the Initiative enters its fifth year, NIH has supported >500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities...
July 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Elisabeth Hansson, Linda Block, Johan Forshammar, Christopher Lundborg, Björn Biber
Background Long-term or chronic pain represents a major health problem and is associated with significant socio-economic costs. During injury, pain can be dissociated from its normal physiological role. It can persist for a longer period of time, even after the primary noxious stimulus has more or less subsided. Analgesic drugs, with predominant neuronal sites of actions, seem to be relatively ineffective. Chronic pain is probably partly a consequence of ongoing neuroinflammation. The mechanisms behind these phenomena, and how the neuronal and non-neuronal activities evoked by painful stimuli and inflammation are processed in the brain and throughout the CNS, are not well understood...
December 29, 2017: Scandinavian Journal of Pain
Tatiana N Olivares-Bañuelos, Isabel Martínez-Hernández, Luisa C Hernández-Kelly, Donají Chi-Castañeda, Libia Vega, Arturo Ortega
Glutamate, the main excitatory neurotransmitter in the vertebrate Central Nervous System, is involved in almost every aspect of brain physiology, and its signaling properties are severely affected in most neurodegenerative diseases. This neurotransmitter has to be efficiently removed from the synaptic cleft in order to prevent an over-stimulation of glutamate receptors that leads to neuronal death. Specific sodium-dependent membrane transporters, highly enriched in glial cells, elicit the clearance of glutamate...
June 13, 2018: Neurochemistry International
Jessica Fernandes, M Vivek Ghate, Sanchari Basu Mallik, Shaila A Lewis
Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-l-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX...
August 25, 2018: International Journal of Pharmaceutics
Catarina Praça, Akhilesh Rai, Tiago Santos, Ana C Cristovão, Sonia L Pinho, Romeo Cecchelli, Marie-Pierre Dehouck, Liliana Bernardino, Lino S Ferreira
Stimulation of adult neurogenesis by targeting the endogenous neural stem cells (NSCs), located in hippocampus and subventricular zone (SVZ), with nanoformulations has been proposed for brain repair in cases of neurodegenerative diseases. Unfortunately, it is relatively unknown the nanoformulation properties to facilitate their accumulation in the neurogenic niches after intravenous injection. Here, we have screened different gold-based formulations having variable morphology, surface chemistry and responsiveness to light for their capacity to cross the blood brain barrier (BBB) and accumulate preferentially in the neurogenic niches...
August 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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