Septimiu Tudor Bucurescu

Neurology at Vital-Klinik, Bad Driburg, Germany

In this paper we describe the case of a Guillain-Barré syndrome patient who was diagnosed with an active yersiniosis and past chlamydiosis. We also discuss the diagnosis, therapy and recovery prognosis of patients with Guillain-Barré syndrome.

DOI: 10.29245/2572.942X/2018/2.1156 View / Download Pdf

Wolf-Dieter Heiss, MD

1Max Planck Institute for Metabolism Research, Cologne, Germany

The diagnosis of cerebral small vessel disease (SVD) is difficult because there is no consensus on clinical criteria and therefore, imaging is important for diagnosis. Most patients undergo brain imaging by computed tomography (CT), which is able to detect ischemic strokes, hemorrhages and brain atrophy and may also indicate white matter changes. Magnetic resonance imaging (MRI) remains the key neuroimaging modality and is preferred to CT in vascular cognitive impairment (VCI) because it has higher sensitivity and specificity for detecting pathological changes. These modalities for imaging morphology permit to detect vascular lesions traditionally attributed to VCI in subcortical areas of the brain, single infarction or lacunes in strategic areas (thalamus or angular gyrus), or large cortical-subcortical lesions reaching a critical threshold of tissue loss. In SVD multiple punctuate or confluent lesions can be seen in the white matter by MRI and were called leukoaraiosis. Another major neuroimaging finding of small vessel disease in VCI are microhemorrhages. However, while CT and MRI are able to detect morphologic lesions, these modalities cannot determine functional consequences of the underlying pathological changes.

Positron emission tomography (PET) can support the clinical diagnosis by visualizing cerebral functions in typically affected brain regions. In SVD, Fluor-Deoxy-Glucose (FDG)-PET can clearly differentiate scattered areas of focal cortical and subcortical hypometabolism that differ from the typical metabolic pattern seen in Alzheimer Dementia (AD) with marked hypometabolism affecting the association areas. Additional PET tracers can further support the diagnosis of a type of dementia and also yield information on the underlying pathophysiology.

DOI: 10.29245/2572.942X/2018/2.1171 View / Download Pdf

Hanna Kalamarz-Kubiak

Department of Genetics and Marine Biotechnology, Institute of Oceanology, Polish Academy of Sciences, Sopot, Poland

DOI: 10.29245/2572.942X/2017/1.1172 View / Download Pdf

Lucia Mendoza-Viveros1,2, Karl Obrietan3, Hai-Ying M. Cheng1,2*

1Department of Biology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada

2Department of Cell and Systems Biology, University of Toronto, Toronto, ON, M5S 3G3, Canada

3Department of Neuroscience, Ohio State University, Columbus, OH, 43210, USA


Daily rhythms in behavior and physiology are coordinated by an endogenous clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This central pacemaker also relays day length information to allow for seasonal adaptation, a process for which melatonin signaling is essential. How the SCN encodes day length is not fully understood. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by directing target mRNAs for degradation or translational repression. The miR-132/212 cluster plays a key role in facilitating neuronal plasticity, and miR-132 has been shown previously to modulate resetting of the central clock. A recent study from our group showed that miR-132/212 in mice is required for optimal adaptation to seasons and non-24-hour light/dark cycles through regulation of its target gene, methyl CpG-binding protein (MeCP2), in the SCN and dendritic spine density of SCN neurons. Furthermore, in the seasonal rodent Mesocricetus auratus (Syrian hamster), adaptation to short photoperiods is accompanied by structural plasticity in the SCN independently of melatonin signaling, thus further supporting a key role for SCN structural and, in turn, functional plasticity in the coding of day length. In this commentary, we discuss our recent findings in context of what is known about day length encoding by the SCN, and propose future directions.

DOI: 10.29245/2572.942X/2017/1.1169 View / Download Pdf

Gizem Yalcin

Department of Medical Biology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey

Sirtuins are highly conserved NAD+-dependent enzymes connected to an increasing set of biological processes. These enzymes have attracted major interest because of their roles in age-related diseases. Sirtuins are implicated in various biological pathways related to stress response, mitochondrial dysfunction, oxidative stress, protein aggregation and inflammatory processes that are intertwined with age-related neurodegenerative diseases.

DOI: 10.29245/2572.942X/2017/1.1168 View / Download Pdf

Nathan Collins MD, Jeffrey Sager MD

Santa Barbara Cottage Hospital Department of Internal Medicine Santa Barbara, CA, USA

Acute laryngeal dystonia (ALD) is a drug-induced dystonic reaction that can lead to acute respiratory failure and is potentially life-threatening if unrecognized. It was first reported in 1978 when two individuals were noticed to develop difficulty breathing after administration of haloperidol. Multiple cases have since been reported with the use of first generation antipsychotics (FGAs) and more recently second-generation antipsychotics (SGAs). Acute dystonic reactions (ADRs) have an occurrence rate of 3%-10%, but may occur more frequently with high potency antipsychotics. Younger age and male sex appear to be the most common risk factors, although a variety of metabolic abnormalities and illnesses have also been associated with ALD as well. The diagnosis of ALD can go unrecognized as other causes of acute respiratory failure are often explored prior to ALD. The exact mechanism for ALD remains unclear, yet evidence has shown a strong correlation with extrapyramidal symptoms (EPS) and dopamine receptor blockade. Recognition and appropriate management of ALD can prevent significant morbidity and mortality.

DOI: 10.29245/2572.942X/2017/1.1167 View / Download Pdf

Khan MI1*

1Orthopedic & Hand surgery, Beverly Hills, CA, USA

DOI: 10.29245/2572.942X/2017/1.1165 View / Download Pdf

Torsak Tippairote1, Dunyaporn Trachootham2*

1BBH Hospital, Bangkok, Thailand

2Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand

Zinc status is an important modifiable factor in Attention Deficit and Hyperactive Disorders (ADHD) and Autistic Spectrum Disorders (ASD), the two most common neurodevelopmental disorders. Many studies reported low serum or plasma zinc level in children with these conditions. While hair zinc level can be obtained non-invasively in young children, the reports of the hair zinc levels in ASD and ADHD children were varied. ASD children were reported to have lower than or indifferent level of hair zinc from that of healthy children. In ADHD children, hair zinc levels were reported as either lower or higher than their healthy control groups. Many factors interplayed and affected measurement of hair zinc level. Until more standardized method has been established, currently the zinc level in hair samples may be used as screening or supporting evidence. Other functional zinc markers such as serum zinc concentrations, dietary zinc intakes, and percentage of stunting rate, are still needed to assess the zinc status in susceptible children.

DOI: 10.29245/2572.942X/2017/10.1158 View / Download Pdf

Zohar Barnett-Itzhaki1,2*, Eli Marom and Eyal Schwartzberg3,4,5

1Public Health Services, Ministry of Health, Jerusalem, Israel

2Bioinformatics department, school of life and health science, Jerusalem College of Technology, Jerusalem, Israel

3Pharmaceutical & Enforcement Divisions, Ministry of Health, 39 Yirmiyahu St., Jerusalem, Israel

4Faculty of Heath Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

5Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, USA

DOI: 10.29245/2572.942X/2017/10.1163 View / Download Pdf

Guoyan Yang1,2, Dennis Chang1, and Jianping Liu2*

1National Institute of Complementary Medicine, Western Sydney University, NSW 2751, Australia
2Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

Background: Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer’s disease.

Methods: This is a commentary on a systematic review that we conducted to evaluate the effectives and safety of Ginkgo biloba in treating mild cognitive impairment or Alzheimer’s disease.

Results: 21 articles with 2608 patients met the inclusion criteria. The general methodological quality of included studies was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer’s disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer’s disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild.

Conclusion: Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer’s disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer’s disease.

DOI: 10.29245/2572.942X/2016/8.1083 View / Download Pdf

Aaron Dadas1,2 Jolewis Washington4, Damir Janigro1,3*

1Flocel Inc., Cleveland, OH, USA
2The Ohio State University, Columbus, OH, USA
3Case Western Reserve University, Cleveland, OH, USA
4John Carroll University, University Heights, OH, USA

The brain is a complex system that requires continual regulation of parenchymal pressure, osmolarity, and waste removal for optimal function; despite this, human brain lacks any obvious extension of lymphatic circulation for moderating fluid and waste regulation. We recapitulate herein a recent analysis of proteinaceous waste deposition in the human brain, its observed route of clearance, and the implications of abnormal accumulation along this clearance pathway as a potential mechanism of neurological diseases. This study uncovered an analogous staining pattern of cerebral phosphorylated tau in temporal lobe epilepsy (TLE) and chronic traumatic encephalopathy (CTE). Regardless of the underlying physiopathology, p-tau elimination occurred via circulation through the perivenous space, as predicted by a glymphatic route of clearance. Remarkably, we demonstrated that p-tau is associated with a neurological disease that can develop independent of head trauma, since in both CTE and TLE: 1) Extracellular p-tau followed unidirectional, fluid-driven pathways that led toward the space bordering large (>100 µm diameter) blood vessels; 2) Tau-positive staining occurred within astroglial cells adjacent to blood vessels, which signified transcellular transport of p-tau as a potential secondary efflux route; 3) P-tau frequently appeared clustered within the perivenous space. This waste aggregation bears significant implications in the disruption of interstitial fluid circulation, which may contribute to exacerbation of disease states. A better understanding of waste elimination in the human brain may prove significant as a therapeutic target to improve parenchymal fluid circulation, and consequently, mitigate the hydrostatic, osmotic and oncotic imbalances that often cause or exacerbate brain diseases.

DOI: 10.29245/2572.942X/2016/7.1082 View / Download Pdf

José Castillo1*, María Isabel Loza2,3, David Mirelman4, Tomás Sobrino1, Francisco Campos1*

1Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela, Spain
2Department of Pharmacology, Universidade de Santiago de Compostela, Discovery group BioFarma, Health Research Institute of Santiago de Compostela, Spain
3BioFarma Research Group, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), University of Santiago de Compostela, Santiago de Compostela, Spain
4Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

Glutamate-excitotoxicity is a primary contributor of ischemic neuronal death. Several strategies have been developed against glutamate-excitotoxicity, however any of them have not showed positive results in the clinical practice so far.

Nowadays, the concept of blood/brain glutamate grabbing is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work, we summarize all experimental data about the potential application of this therapy against stroke pathology.

Ischemic stroke, caused by interruption of the blood supply to the brain, is one of the most important causes of morbidity and mortality worldwide. Currently, the control of systemic parameters, such as body temperature, blood pressure, and glycemia, has considerably improved the outcome of stroke patients. In the absence of protective therapy, an early artery reperfusion, i.e. mechanical or enzymatic thrombolysis, remains the primary goal of treatment for acute ischemic stroke. However, because of the progressive increase in stroke incidence, the high morbidity and the limited therapeutic tools against stroke, seeking new alternatives that can be applied more universally and with less technological requirements is in high demand1, 2.

DOI: 10.29245/2572.942X/2016/3.1030 View / Download Pdf

Bernd Krone

1Center for Hygiene and Human Genetics, University Göttingen, Göttingen, Germany
2Medical Laboratory, Kurt-Reuber-Haus, Herkulesstraße 34a, 34119 Kassel, Germany

The sporadic forms of motor neuron diseases seem to depend on a multitude of factors that are, however, largely speculative. A main endogenous factor is seen in the enhanced expression of human endogenous retroviruses (HERVs). It is supposed that this is affecting the biogenesis of neuromelanin, in particular in the locus coeruleus. An altered neuromelanin with increased storage of metals and of precursors for toxins from food, respectively, might be of central importance. A hypothesis is described that is able to explain a number of observations and to understand roles and interactions of different factors. Toxins affecting the excitatory system are formed apparently within altered neuromelanin. Moreover, neuromelanin loaded with metal is also a microenvironment where pathological variants of proteins such as of alpha-synuclein are generated. Familial and toxin related forms of the diseases merge in formation and deposition of aberrant proteins and in a failure to destroy superoxide, thus increasing the harm from oxidative and nitrosative stress. This view might give some rational to revive investigations in methods for stabilization of storage and cautious squeezing out of metals and toxicants from neuromelanin, relying eventually on melatonin, iron chelators and chloroquine, respectively.

DOI: 10.29245/2572.942X/2016/2.1015 View / Download Pdf

Kurt A. Jellinger

Institute of Clinical Neurobiology, Vienna, Austria

Multiple system atrophy (MSA) is a fatal orphan neurodegenerative disorder that manifests with autonomic, parkinsonian, cerebellar, and pyramidal features. It is characterized by the accumulation of misfolded α-synuclein (αSyn) in oligodendroglia and neurons, affecting multiple parts of the central, autonomic and perípheral system. Both the etiology and pathogenesis of MSA are unknown, although a genetic component has been proposed. Accumulation of aberrant αSyn in oligodendrocytes, preceded by relocation of p25α protein from myelin into oligodendroglia, results in the formation of insoluble glial cytoplasmic inclusions (GCIs). These changes are associated with proteasomal, mitochondrial and lipid transport dysfunction, oxidative stress, reduced trophic transport, neuroinflammation and other noxious factors. Their interaction induces dysfunction of the oligodendroglial-myelin-axon-neuron complex, resulting in the system-specific pattern of neurodegeneration characterizing MSA as a synucleinopathy with oligodendroglio-neuronopathy. Propagation of modified toxic αSyn species from neurons to oligodendroglia by "prion-like" transfer and its spreading to associate neuronal pathways result in multi-system involvement. No reliable biomarkers are currently available for the clinical diagnosis and prognosis of MSA and neither effective neuroprotective nor disease-modifying therapies of MSA are available, although novel treatment strategies targeting αSyn are under discussion. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes to develop reliable diagnostic biomarkers and to deliver targets for effective treatment of this hitherto incurable disorder is urgently needed.

DOI: 10.29245/2572.942X/2016/1.1002 View / Download Pdf

Logan McCool1, Michel Kliot2, Danqing Guo3, Danzhu Guo3

1Department of Rehabilitation Medicine, University of Minnesota School of Medicine, Minneapolis MN 55455, USA
2Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, CA 94304, USA
3BayCare Clinic, Green Bay, WI 54303, USA

There have been many advances in recent years in peripheral nerve releases and most notably those involving median nerve entrapment at the wrist. This mini-review article focuses on the advances within the past five years in minimally, percutaneous, and ultra-minimally invasive techniques for carpal tunnel release. The progress in these surgical techniques has been made in part by the improvements in real time sonographic imaging. With each surgical technique, we look at the pre-clinical and clinical data and any complications from or limitations with these procedures. It is our aim with this article to spark discussion and spur innovation regarding ultrasound guided carpal tunnel release that can be applied to other peripheral nerve entrapments.

In the past five years, the surgical techniques to perform carpal tunnel release continue to advance. Among these surgical techniques is a growing trend towards less invasive methods and increased utilization of ultrasound guidance. In the literature, the list of methods includes open release, endoscopic release, minimally invasive release, percutaneous release, and ultra-minimally invasive release. These progressively less invasive techniques take advantage of the major improvements in both ultrasound image quality and real-time definition. This mini-review examines various surgical techniques involving minimally invasive, percutaneous, and ultra-minimally carpal tunnel release with emphasis on the development of techniques that are increasingly less invasive and more reliant on high-quality ultrasound imaging.

DOI: 10.29245/2572.942X/2017/10.1157 View / Download Pdf

Yumiko Watanabe1, N.A.R. Nik-Mohd-Afizan1,2, Ichiro Takashima1*

1Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba 305-8568, Japan
2Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Noninvasive brain stimulation methods, including repetitive transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), have received considerable attention in recent years for use in the study and treatment of neurological conditions. Of these methods, tDCS is considered particularly promising due to its ease of use and ability to confer polarity-dependent effects on brain excitability, making it an excellent option for clinical treatment of neurological and psychiatric diseases. While generally regarded as safe when following standard protocols, the effects of tDCS on cerebral blood vessels and blood-brain barrier (BBB) functions remain poorly understood. Here, we provide an overview of tDCS in the context of BBB function, summarize the current literature, and discuss implications for future research. To date, no alterations or damage to the BBB have been reported after weak tDCS stimulations in human subjects; however, some animal studies have reported alterations to BBB function following increased tDCS intensity, with inconsistencies in the effective tDCS polarity used to produce these BBB disruptions between studies. Further research will be necessary to evaluate the effects of tDCS on the BBB under various conditions. Finally, we discuss the potential of tDCS for enhancing drug delivery to the central nervous system, which may become possible as we refine our understanding of the effects of tDCS on BBB permeability.

DOI: 10.29245/2572.942X/2017/10.1162 View / Download Pdf

Fritz-Olaf Lehmann, PhD

Department of Animal Physiology, University of Rostock, Germany

Rhythmic locomotor behavior in animals requires exact timing of muscle activation within the locomotor cycle. Neural strategies for timing control that employ higher brain function, however, suffer from synaptic and neural transmission delays, making them inefficient for control of fast-frequent locomotor systems. Evolutionary pressure on muscle timing control is particularly pronounced in flying insects with wing flapping periods of few milliseconds. In these animals, sensory integration is often achieved at the level of the peripheral nervous system, circumventing the central brain and controlling spike activation phases with little delay, rather than muscle spike frequency. This review is engaged in the precision with which flies adjust power output of their flight muscles and highlights the significance of visual and proprioceptive feedback loops for muscle spike control. Recent results suggest that in flies peripheral feedback loops are keys enabling precise heading control and body stability in flight, and potentially similar to the function of local circuits for locomotor control found in the spinal chord of vertebrates.

DOI: 10.29245/2572.942X/2017/9.1153 View / Download Pdf

Tomoyuki Nishizaki*

Innovative Bioinformation Research Organization, 2-3-14 Katsuragi, Kita-ku, Kobe 651-1223, Japan

Alzheimer’s disease (AD) is characterized by extensive deposition of amyloid β (Aβ) and formation of neurofibrillary tangles (NFTs) consisting of hyperphosphorylated Tau. So far, a variety of AD drugs targeting Aβ have been developed, but ended in failure. A recent focus on AD therapy, therefore, is development of Tau-targeted drugs. Aβ activates glycogen synthase kinase-3β (GSK-3β), that plays a central role in Tau phosphorylation, responsible for NFT formation. The linoleic acid derivative DCP-LA has been developed as a promising drug for AD therapy. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA restrains Tau phosphorylation efficiently due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase/insulin receptor substrate 1/phosphoinositide 3-kinase/3-phosphoinositide-dependent protein kinase 1/Akt-mediated inactivation of GSK-3β in association with PTP1B inhibition. Moreover, DCP-LA ameliorates spatial learning and memory impairment in 5xFAD transgenic mice, an animal model of AD. Consequently, combination of PKCβ activation and PTP1B inhibition must be an innovative strategy for AD therapy.

DOI: 10.29245/2572.942X/2017/9.1159 View / Download Pdf

Nishant Ranjan Chauhan1, Rajinder Kumar Gupta1, Shashi Bala Singh2*

1Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
2Distinguished Scientist and Director General (Life Sciences), Defence Research and Development Organisation (DRDO), DRDO Bhawan, Rajaji Marg, Delhi 110011, India

Heat stress (HS) is a common stressor that affects all biological systems. Mild to moderate HS is associated with intact baroreflex response which tries to cope up with the stress by maintaining mean arterial pressure (MAP). However, during severe HS, baroreflex response fails leading to fall in MAP which is a pathognomonic feature of heat stroke. Heat stroke can induce neuroinflammation, brain ischemia, oxidative stress and neuronal damage. Increase in ambient temperature led to activation of the thermoregulatory process in Hypothalamus (HTH) and was achieved by rise in nor-epinephrine and fall in serotonin, whereas neurotransmitter imbalance occurred during severe HS in HTH and was associated with expression of inflammatory mediators. Results of our preliminary study also suggested that neuroinflammation was associated with neurotransmitter (monoamines and glutamate) imbalance in HTH leading to thermoregulatory disruption during severe HS. Here, we also discussed that individuals predisposed to factors like chronic inflammation and other complications could decrease the threshold of heat tolerance since a short episode of even sub maximal heat exposure would precipitate the inflammatory cascade leading to thermoregulatory shutdown.

DOI: 10.29245/2572.942X/2017/9.1150 View / Download Pdf

Francisco José Sanz1,2, Cristina Solana-Manrique1,2, Verónica Muñoz-Soriano1,2 and Nuria Paricio1,2,*

1Departamento de Genética, Facultad CC Biológicas, Universidad de Valencia, 46100 Burjassot, Spain
2Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, 46100 Burjassot, Spain

DOI: 10.29245/2572.942X/2017/9.1149 View / Download Pdf

Lingyu Qiu, Huiqiang Lu*

Jiangxi Province Key Laboratory of Developmental Biology of Organs, Jiangxi Engineering laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Center for Developmental biology of Jinggangshan University, College of life sciences, Jinggangshan University, Ji’an, Jiangxi 343009, China

Neuronal apoptosis is an important pathophysiological factor of Alzheimer’s disease (AD). Inhibition of endoplasmic reticulum stress (ERS)-induced neuronal apoptosis is an effective strategy to deal with AD. In this commentary, we summarize the relationship between AD and ERS injury-induced neuronal apoptosis, and highlight the protective effects and mechanism of isorhamnetin (Iso) against ERS-induced injury in N2a cells. Moreover, this commentary discusses the recent findings in the role of Iso in other diseases.

DOI: 10.29245/2572.942X/2017/9.1160 View / Download Pdf

Takako Takemiya

Medical Research Institute, Tokyo Women’s Medical University, Shinjuku, Tokyo 162-8666, Japan

Astrocytes interact closely with neurons via glutamate; this astrocyte-neuron circuit may play a pivotal role in synaptic transmission. In addition, astrocytes contact vascular endothelial cells (ECs) with their end-feet; therefore, ECs may have some role in regulating neuronal activity via astrocytes in the brain. In our studies, we found that kainic acid (KA) microinjection induced the expression of microsomal prostaglandin E synthase-1 (mPGES-1) in venous ECs and the expression of the prostaglandin E2 (PGE2) receptor EP3 on astrocytes. Moreover, endothelial mPGES-1 exacerbated KA-induced neuronal injury in the mouse brain. In in vitro experiments, mPGES-1 produced PGE2, which increased astrocytic Ca2+ levels and Ca2+-dependent glutamate release, thus aggravating neuronal injury. We found ECs had a role under pathological conditions and brain ECs are not merely a physiological barrier between the blood and brain; instead, they may also act as a signal transducer or amplifier. Moreover, the endothelium-astrocyte-neuron signaling pathway may be crucial for driving neuronal injury elicited by repetitive seizures and may be a new therapeutic target for epilepsy.

DOI: 10.29245/2572.942X/2017/8.1148 View / Download Pdf

Benoit Michot1

1Department of Endodontics, New York University - College of Dentistry, 345 E. 24th Street 1008S, New York, NY 10010, United States.

DOI: 10.29245/2572.942X/2017/8.1147 View / Download Pdf

José M. Brito-Armas and Rafael Castro-Fuentes*

Department of Basic Medical Sciences, University of La Laguna, Tenerife, Spain

 

DOI: 10.29245/2572.942X/2017/8.1144 View / Download Pdf

Marilene Demasi and Bruna Franciele Faria

Laboratory of Biochemistry and Biophysics, Instituto Butantan, São Paulo-SP, Brazil

Since the discovery of the proteasome (1986), many years passed before researchers explored the benefits of its activation. However, its inhibition, which was first observed in the beginning of the 1990s, gained wide acceptance because of its anti-tumor effect, as proteasome inhibition induces apoptosis. Currently, a proteasome inhibitor is utilized as a clinical tool. However, proteasome activation has been shown to either extend the life span of many cellular and animal models or prevent the accumulation of protein aggregates. Later effect might have an important contribution to neurodegenerative diseases with the hallmark of protein aggregation and the impairment of the proteasome. This short review presents prominent data on proteasome activation, focusing on the 20S catalytic proteasome particle. In addition, the benefits and consequences of proteasome activation in tumor development and progression are discussed.

DOI: 10.29245/2572.942X/2017/8.1146 View / Download Pdf