All Articles

Valeria Belleudi¹, Nera Agabiti^1*, Marina Davoli¹, Danilo Fusco¹

¹Department of Epidemiology, Lazio Regional Health Service, Via Cristoforo Colombo, 112, 00147 Rome, Italy

Kathleen Monahan, D.S.W., L.C.S.W., L.M.F.T.

Associate Professor Director, Trauma Specialization Stony Brook School of Social Welfare 101 Nicolls Road Health Sciences Center, Level 2 Stony Brook, NY, USA

Intimate Partner Violence (IPV) remains at epidemic proportions in the United States. Traumatic Brain Injury (TBI) as an outcome of IPV is now being investigated by researchers, particularly long-term sequelae. This review addresses underreporting and lack of treatment, and the physical and psychological impact for victims of IPV who have received a TBI. Recent research has begun to investigate professional sports players who experience repeated concussions and their at-risk status for Chronic Traumatic Encephalopathy (CTE). Women who are in abusive relationships for long periods of time may also incur repeated blows to the head. Researching the at-risk status for CTE is a much needed line of inquiry for this underserved population.

Gerhard Ransmayr

Dept. of Neurology 2, Kepler University Hospital, Krankenhausstr 9, A-4020 Linz, Austria

Apostolos P. Georgopoulos^1,2*, Effie-Photini C. Tsilibary^1,2, Eric P. Souto¹, Lisa M. James^1,2, Brian E. Engdahl^1,2, Angeliki Georgopoulos³

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota

³Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota

Gulf War Illness (GWI) is a chronic debilitating disease of unknown etiology that affects the brain and has afflicted many veterans of the 1990-91 Gulf War (GW). Here we tested the hypothesis that brain damage may be caused by circulating harmful substances to which GW veterans were exposed but which could not be eliminated due to lack of specific immunity. We assessed the effects of serum from GWI patients on function and morphology of brain cultures in vitro, including cultures of embryonic mouse brain and neuroblastoma N2A line. Blood serum from GWI and healthy GW veterans was added, alone and in combination, to the culture and its effects on the function and morphology of the culture assessed. Neural network function was assessed using electrophysiological recordings from multielectrode arrays in mouse brain cultures, whereas morphological assessments (neural growth and cell apoptosis) were done in neuroblastoma cultures. In contrast to healthy serum, the addition of GWI serum disrupted neural network communication and caused reduced cell growth and increased apoptosis. All of these detrimental effects were prevented or ameliorated by the concomitant addition of serum from healthy GW veterans. These findings indicate that GWI serum contains neuropathogenic factors that can be neutralized by healthy serum. We hypothesize that these factors are persistent antigens circulating in GWI blood that can be neutralized, possibly by specific antibodies present in the healthy serum, as proposed earlier¹.

Elke Kalbe^1*, Ann-Kristin Folkerts¹

¹ Medical Psychology | Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Cologne, Kerpenerstraße 62, 50937 Cologne, Germany

While it is undeniable that cognitive stimulation (CS) is effective in patients with dementia, there is still a lack of understanding of the underlying mechanisms of the effects, and questions like “Who benefits?” or “Which factors determine the benefits?” are not yet answered. Therefore, this commentary gives an overview of different aspects (e.g., sociodemographic factors, disease characteristics, living setting) that need to be considered while doing research on CS to understand their impact on CS effects. It is also necessary to examine the effects of CS in real-life settings (e.g., geriatric hospitals) with mixed samples (e.g., patients with different severity of dementia). Additionally, important factors for future studies on CS in dementia (e.g., reporting according to the CONSORT guidelines, more health-economics studies) are outlined.

M Mirzaei^{1,2,3 *}, V B Gupta⁴, V K Gupta²

¹Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia

²Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia

³Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia

⁴School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia

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.

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.

Hanna Kalamarz-Kubiak

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

Lucia Mendoza-Viveros^1,2, Karl Obrietan³, Hai-Ying M. Cheng^1,2*

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.

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.

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.

Khan MI^1*

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

Torsak Tippairote¹, Dunyaporn Trachootham^2*

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.

Zohar Barnett-Itzhaki^1,2*, Eli Marom and Eyal Schwartzberg^3,4,5

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

Logan McCool¹, Michel Kliot², Danqing Guo³, Danzhu Guo³

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.

Yumiko Watanabe¹, N.A.R. Nik-Mohd-Afizan^1,2, Ichiro Takashima^1*

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.

Lingyu Qiu, Huiqiang Lu*

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.

Fritz-Olaf Lehmann, PhD

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.

Tomoyuki Nishizaki*

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.

Nishant Ranjan Chauhan¹, Rajinder Kumar Gupta¹, Shashi Bala Singh^2*

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.

Francisco José Sanz^1,2, Cristina Solana-Manrique^1,2, Verónica Muñoz-Soriano^1,2 and Nuria Paricio^1,2,*

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.

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

Benoit Michot¹