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https://www.readbyqxmd.com/read/29786802/-treatment-with-neurostimulation-and-ketogenic-diet-for-people-with-medically-refractory-epilepsy
#1
Eva Kumlien, Tove Hallbook, Maria Dahlin
For some people with medically refractory epilepsy adjunct treatment with neurostimulation and ketogenic diet can be an option. Vagal nerve stimulation, VNS, consists of chronic intermittent electrical stimulation of the vagus nerve. VNS is effective and well tolerated in adolescents and adults. There is insufficient evidence on the efficacy of deep brain stimulation, DBS, and brain-responsive neurostimulation, RNS. Ketogenic diet is an established treatment in epilepsy with an increased number of indications, especially in neurometabolic diseases, where dietary therapy can completely eliminate epilepsy and improve cognitive and motor development...
May 22, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29786697/imaging-glutathione-depletion-in-the-rat-brain-using-ascorbate-derived-hyperpolarized-mr-and-pet-probes
#2
Hecong Qin, Valerie N Carroll, Renuka Sriram, Javier E Villanueva-Meyer, Cornelius von Morze, Zhen Jane Wang, Christopher A Mutch, Kayvan R Keshari, Robert R Flavell, John Kurhanewicz, David M Wilson
Oxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized 13 C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species accumulation) in vivo...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29786658/melatonin-as-a-therapy-for-traumatic-brain-injury-a-review-of-published-evidence
#3
REVIEW
Nicole Osier, Emily McGreevy, Lan Pham, Ava Puccio, Dianxu Ren, Yvette P Conley, Sheila Alexander, C Edward Dixon
Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786451/annexin-a2-is-a-robo4-ligand-that-modulates-arf6-activation-associated-cerebral-trans-endothelial-permeability
#4
Wenlu Li, Zhigang Chen, Jing Yuan, Zhanyang Yu, Chongjie Cheng, Qiuchen Zhao, Lena Huang, Katherine A Hajjar, Zhong Chen, Eng H Lo, Haibin Dai, Xiaoying Wang
Blood-brain barrier (BBB) disruption in neurological disorders remains an intractable problem with limited therapeutic options. Here, we investigate whether the endothelial cell membrane protein annexin A2 (ANXA2) may play a role in reducing trans-endothelial permeability and maintaining cerebrovascular integrity after injury. Compared with wild-type mice, the expression of cerebral endothelial junctional proteins was reduced in E15.5 and adult ANXA2 knockout mice, along with increased leakage of small molecule tracers...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29786109/engulfment-of-platelets-delays-endothelial-cell-aging-via-girdin-and-its-phosphorylation
#5
Yong Lan, Yongjun Li, Dajun Li, Peng Li, Jiyang Wang, Yongpeng Diao, Guodong Ye, Yangfang Li
Endothelial cells are critical in angiogenesis and maintain the homeostasis of the blood‑brain barrier (BBB). Platelets (PLTs) are essential in vascular biology, including angiogenesis. The present study aimed to investigate the effect of PLTs on the aging of endothelial cells. Human brain microvascular endothelial cells (HBMECs) and human astrocytes were co‑cultured to mimic the BBB. Transmission electron microscopy was used to observe the engulfment of PLTs. Confocal microscopy was used to observe the co‑localization of PLTs, girders of actin filament (girdin) and phosphorylated (p‑)girdin...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29785578/transport-of-the-pituitary-adenylate-cyclase-activating-polypeptide-across-the-blood-brain-barrier-implications-for-migraine
#6
Faisal Mohammad Amin, Henrik Winther Schytz
BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behind PACAP-induced migraine attacks, but also to develop antimigraine drugs targeting the PACAP receptors Here, we aim to review the transport ability of PACAP across the BBB. METHODS: We performed a systematic literature search on PubMed to identify studies reporting original data on PACAP and BBB...
May 21, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29784823/continuous-intrathecal-orexin-delivery-inhibits-cataplexy-in-a-murine-model-of-narcolepsy
#7
Mahesh K Kaushik, Kosuke Aritake, Aya Imanishi, Takashi Kanbayashi, Tadashi Ichikawa, Tetsuo Shimizu, Yoshihiro Urade, Masashi Yanagisawa
Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783725/polyphenols-in-parkinson-s-disease-a-systematic-review-of-in-vivo-studies
#8
REVIEW
Małgorzata Kujawska, Jadwiga Jodynis-Liebert
Parkinson's disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier...
May 19, 2018: Nutrients
https://www.readbyqxmd.com/read/29782961/baclofen-induced-encephalopathy-in-overdose-modeling-of-the-electroencephalographic-effect-concentration-relationships-and-contribution-of-tolerance-in-the-rat
#9
Magali Chartier, Isabelle Malissin, Salma Tannous, Laurence Labat, Patricia Risède, Bruno Mégarbane, Lucie Chevillard
Baclofen, a γ-amino-butyric acid type-B receptor agonist with exponentially increased use at high-dose to facilitate abstinence in chronic alcoholics, is responsible for increasing poisonings. Baclofen overdose may induce severe encephalopathy and electroencephalographic (EEG) abnormalities. Whether prior prolonged baclofen treatment may influence the severity of baclofen-induced encephalopathy in overdose has not been established. We designed a rat study to characterize baclofen-induced encephalopathy, correlate its severity with plasma concentrations and investigate the contribution of tolerance...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782834/high-throughput-dissection-of-aav-host-interactions-the-fast-and-the-curious
#10
REVIEW
Anne-Kathrin Herrmann, Dirk Grimm
Over fifty years after its initial description, Adeno-associated virus (AAV) remains a most exciting but also most elusive study object in basic or applied virology. On the one hand, its simple structure not only facilitates investigations into virus biology, but combined with the availability of numerous natural AAV variants with distinct infection efficiency and specificity also makes AAV a preferred substrate for engineering of gene delivery vectors. On the other hand, it is striking to witness a recent flurry of reports that highlight and partially close persistent gaps in our understanding of AAV virus and vector biology...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782323/role-of-blood-brain-barrier-in-alzheimer-s-disease
#11
Zhiyou Cai, Pei-Feng Qiao, Cheng-Qun Wan, Min Cai, Nan-Kai Zhou, Qin Li
The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782166/toxicokinetics-tissue-distribution-and-excretion-of-dufulin-racemate-and-its-r-s-enantiomers-in-rats
#12
Huaguo Chen, Xin Zhou, Baoan Song
Dufulin is a plant antiviral agent with a novel molecular structure and has been used widely to prevent and control tobacco and rice viral diseases. In this study, an UHPLC-MS/MS assay was developed for rapid determination of dufulin racemate (rac-DFL) and its R (S)-enantiomers in rat plasma, tissues, urine and feces. A MALDI-MSI method was further used to visual research on tissue distribution after oral administration of the three analytes. Toxicokinetic study showed that both (R)-enantiomers of dufulin ((R)-DFL) and (S)-enantiomers of dufulin ((S)-DFL) had a faster ability to reach Cmax than that of rac-DFL...
May 21, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29782001/a-simple-and-reproducible-method-to-prepare-membrane-samples-from-freshly-isolated-rat-brain-microvessels
#13
Hrvoje Brzica, Wazir Abdullahi, Bianca G Reilly, Patrick T Ronaldson
The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins...
May 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29780671/protection-of-cultured-brain-endothelial-cells-from-cytokine-induced-damage-by-%C3%AE-melanocyte-stimulating-hormone
#14
András Harazin, Alexandra Bocsik, Lilla Barna, András Kincses, Judit Váradi, Ferenc Fenyvesi, Vilmos Tubak, Maria A Deli, Miklós Vecsernyés
The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells...
2018: PeerJ
https://www.readbyqxmd.com/read/29779956/targeted-covalent-inhibition-of-prolyl-oligopeptidase-pop-discovery-of-sulfonylfluoride-peptidomimetics
#15
Salvador Guardiola, Roger Prades, Laura Mendieta, Arwin J Brouwer, Jelle Streefkerk, Laura Nevola, Teresa Tarragó, Rob M J Liskamp, Ernest Giralt
Prolyl oligopeptidase (POP), a serine protease highly expressed in the brain, has recently emerged as an enticing therapeutic target for the treatment of cognitive and neurodegenerative disorders. However, most reported inhibitors suffer from short duration of action, poor protease selectivity, and low blood-brain barrier (BBB) permeability, which altogether limit their potential as drugs. Here, we describe the structure-based design of the first irreversible, selective, and brain-permeable POP inhibitors. At low-nanomolar concentrations, these covalent peptidomimetics produce a fast, specific, and sustained inactivation of POP, both in vitro and in human cells...
May 7, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29779945/moderate-uv-exposure-enhances-learning-and-memory-by-promoting-a-novel-glutamate-biosynthetic-pathway-in-the-brain
#16
Hongying Zhu, Ning Wang, Lei Yao, Qi Chen, Ran Zhang, Junchao Qian, Yiwen Hou, Weiwei Guo, Sijia Fan, Siling Liu, Qiaoyun Zhao, Feng Du, Xin Zuo, Yujun Guo, Yan Xu, Jiali Li, Tian Xue, Kai Zhong, Xiaoyuan Song, Guangming Huang, Wei Xiong
Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus...
May 7, 2018: Cell
https://www.readbyqxmd.com/read/29779881/failure-of-tafamidis-to-halt-progression-of-ala36pro-ttr-oculomeningovascular-amyloidosis
#17
Fabrizio Salvi, Roberto Volpe, Francesca Pastorelli, Andrea Bianchi, Alessandra Vella, Claudio Rapezzi, Mario Mascalchi
Oculomeningovascular amyloidosis is a variant of transthyretin (TTR) amyloidotic polyneuropathy, which is associated with blindness and brain ischemia, microhemorrages, and siderosis due to prominent production of the abnormal TTR in the eye and in the choroid plexuses. Tafamidis is a TTR stabilizer that is orally administered and, by interfering with amyloid fibril formation and deposition, is capable of slowing progression of TTR polyneuropathy and of early-stage cardiomyopathy. However, the ocular manifestations of amyloid deposition progressed despite tafamidis therapy in Val30Met TTR amyloidosis, and the effects of tafamidis on meningovascular amyloidosis are unknown...
May 17, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29778535/lysophosphatidic-acid-receptor-lpa-6-regulates-endothelial-blood-brain-barrier-function-implication-of-hepatic-encephalopathy
#18
Kayo Masago, Yasuyuki Kihara, Keisuke Yanagida, Fumie Hamano, Shinsuke Nakagawa, Masami Niwa, Takao Shimizu
Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777919/brain-to-bone-what-is-the-contribution-of-the-brain-to-skeletal-homeostasis
#19
REVIEW
Anna Idelevich, Roland Baron
The brain, which governs most, if not all, physiological functions in the body, from the complexities of cognition, learning and memory, to the regulation of basal body temperature, heart rate and breathing, has long been known to affect skeletal health. In particular, the hypothalamus - located at the base of the brain in close proximity to the medial eminence, where the blood-brain-barrier is not as tight as in other regions of the brain but rather "leaky", due to fenestrated capillaries - is exposed to a variety of circulating body cues, such as nutrients (glucose, fatty acids, amino acids), and hormones (insulin, glucagon, leptin, adiponectin) [1-3]...
May 16, 2018: Bone
https://www.readbyqxmd.com/read/29777754/hmgb1-neutralization-attenuates-hippocampal-neuronal-death-and-cognitive-impairment-in-rats-with-chronic-cerebral-hypoperfusion-via-suppressing-inflammatory-responses-and-oxidative-stress
#20
Yue Hei, Rong Chen, Xicai Yi, Qianfa Long, Dakuan Gao, Weiping Liu
High mobility group box-1 (HMGB1) acts as a proinflammatory molecule once released into the extracellular space and inhibition of HMGB1 signaling has been reported be neuroprotective in neurodegenerative diseases. Besides, chronic cerebral hypoperfusion (CCH) causes cognitive impairment in neurodegenerative diseases. Here we tested the protective role of HMGB1 inhibition using anti-HMGB1 neutralizing antibody (Ab) against CCH in rats after bilateral common carotid artery occlusion (2VO). 169 male Sprague-Dawley rats underwent 2VO or sham operation...
May 16, 2018: Neuroscience
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