Alejandra N. Martinez1, Mario T. Philipp1,2

1Division of Bacteriology & Parasitology, Tulane National Primate Research Center, Covington, LA, USA
2Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, LA, USA

This review addresses the role that substance P (SP) and its preferred receptor neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. The SP/NK1R complex is a key player in the interaction between the immune and nervous systems. A common effect of this interaction is inflammation. For this reason and because of the predominance in the human brain of the NK1R, its antagonists are attractive potential therapeutic agents. Preventing the deleterious effects of SP through the use of NK1R antagonists has been shown to be a promising therapeutic strategy, as these antagonists are selective, potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to clinical management of CNS inflammation.

DOI: 10.29245/2572.942X/2016/2.1020 View / Download Pdf

Gabriele C Saretzki

Institute for Cell and Molecular Biosciences, Newcastle Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, UK

Telomerase is best known for its canonical function in telomere maintenance. However, a growing number of non-telomeric functions have been described. Several groups have found the telomerase protein TERT to persist in adult brain neurons. A protective role for the telomerase protein TERT had been demonstrated in cultivated mouse neurons during brain development, against excitotoxic stresses from N-methyl-D-aspartate (NMDA) and glutamate and agents known to be involved in neurodegenerative diseases such as beta amyloid peptides and hyperphosphorylated tau. In contrast, lack of telomerase and TERT protein increase oxidative stress and decrease neuronal survival. Research on telomerase and TERT protein in human neurodegenerative diseases is a relatively new field. However, there is emerging evidence of a beneficial role of telomerase in human brains and animal models of neurodegenerative diseases that suggests to explore the possibility of using telomerase activators as neuroprotective agents to combat brain ageing and to ameliorate neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. The current mini-review summarises the knowledge about this developing novel area of brain research.

DOI: 10.29245/2572.942X/2016/2.1025 View / Download Pdf

Riikka-Liisa Uronen, Henri J. Huttunen*

Neuroscience Center, University of Helsinki, FI-00014 Helsinki, Finland

In Alzheimer’s disease (AD), loss of neurons and synapses parallels the formation of neurofibrillary tangles, protein aggregates mainly composed of hyperphosphorylated and aggregated Tau protein. Tau is mostly a cytosolic protein but can also be secreted by neurons. Cell-to-cell transfer of misfolded Tau protein plays a key role in the spread of neurofibrillary pathology between brain regions in AD and other tauopathies. Advances in genome-wide technologies have identified a large number of genetic risk factors for late-onset AD (LOAD). Currently, it remains unknown if genetic factors influence disease risk or progression rate by altering cell-to-cell propagation of Tau. Several LOAD risk genes are functionally associated with endocytic trafficking providing a potential link to Tau secretion and uptake. Recently, a LOAD risk gene FRMD4A was shown to regulate Tau secretion via a pathway linked to presynaptic vesicle machinery and polarity signaling. Tau release is linked to neuronal activity, and genetic factors that affect presynaptic vesicle release in the aging brain may also influence disease progression in AD and other tauopathies. In this mini review, we summarize the recent literature with a focus on the role of FRMD4A-cytohesin-Arf6 pathway and presynaptic vesicle machinery in the secretion of Tau.

DOI: 10.29245/2572.942X/2016/2.1022 View / Download Pdf

Domingos J1,3, Godinho C1,2,3, Ferreira JJ1,3,4*

1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal
2Center for Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal
3CNS-Campus Neurológico Sénior, Portugal
4Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

Technologies may have implications for improving clinical diagnosis and prognosis, and for the development of therapeutic interventions, specific biomarkers, and preventive strategies. Given the amount of existing and ever-growing quantitative assessments using technology in PD, clinicians, patients and researchers are faced with the challenge of deciding which assessment tool to use in the laboratory, clinic and home environment. In order to facilitate this decision-making a systematic review was done to identify and classify the available monitoring technologies for individuals with PD over the last 2 decades. This is a commentary on the systematic review which adds on discussion on some controversial issues in the area. It tackles some of current open-to-discussion topics in the technology field, such as: which definitions to use, the heterogeneity of the clinimetric properties among technologies, standardization of a validation process, how to group different measuring technologies, and the need to conduct further studies on existing technologies before developing new ones. The strength of this comprehensive, timely and useful review is the detailed and robust approach taken by authors to classify technologies as listed, suggested, or recommended for the assessment of individuals with PD.

DOI: 10.29245/2572.942X/2016/2.1013 View / Download Pdf

Nathalie Khoury, Kevin B. Koronowski and Miguel A. Perez-Pinzon*

Department of Neurology and Neuroscience Program, Cerebral Vascular Disease Research Laboratories, Miller School of Medicine, University of Miami, Miami, Florida, USA

In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive. In the below commentary we discuss potential mechanisms that could explain this novel extended window of ischemic tolerance in the context of previously identified windows and the known mechanisms behind them. We also draw parallels from the fields of hibernation and hypoxia-tolerance, which are chronic adaptations to severe conditions of hypoxia and ischemia known to be mediated by a form of metabolic depression. We also briefly discuss the importance of epigenetic modifications in maintaining this depressed state of metabolism.

DOI: 10.29245/2572.942X/2016/2.1021 View / Download Pdf

Godinho C1,2,3, Domingos J1,3, Domingos J1,3,4*

1Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal
2Center for Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugale
3CNS-Campus Neurológico Sénior, Torres Vedras, Portugal
4Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

Healthcare professionals and pharmaceutical companies invest a great amount of time and effort in continuously creating electronic health solutions. These technology system developments may represent a step forward in care as ultimately it is not possible to manage what cannot be evaluated.

Yet, the use of future generations of technology depends on their specific design, fabrication, distribution, and, most importantly, patients adopting these new technologies as life companions. Data management and the use of artificial intelligence appear as new technological challenges. The overload, sharing and handling of information give rise to new legal, social, and ethical discussions in a field where there is a lack of universal criteria for data ownership, privacy and sharing.

Future technological progress requires much cooperation between multidisciplinary teams including sufficient sharing and benchmarking within open access frameworks.

DOI: 10.29245/2572.942X/2016/1.1019 View / Download Pdf

Wolfgang H Jost

Department of Neurology, University of Freiburg, Germany

For years we have been injecting botulinum toxin relying mainly on our clinical experience and, in some cases, on the use of electromyography. Within that time some therapists introduced sonography for guidance and emphasize the advantages of this technique. Schramm et al., for example, pointed out the relevance of sonography for botulinum toxin treatment in cervical dystonia. Within a short time the importance of sonography has been well documented in this indication. Even assuming a critical distance, the significance of this technique has become largely indisputable.

DOI: 10.29245/2572.942X/2016/1.1010 View / Download Pdf

Mélanie H. Thomas1, Sandra Pelleieux1,2, Nicolas Vitale3, Jean Luc Olivier1,2*

1Unité de Recherche Aliment et Fonctionnalité des Produits Animaux (URAFPA), INRA USC 0340, Université de Lorraine, Nancy, France
2Service de Biochimie-Biologie Moléculaire, Hôpital Central, CHU de Nancy, Nancy, France
3Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR CNRS 3212, Université de Strasbourg, Strasbourg, France

Alzheimer’s disease is a very complex disease in which neuroinflammation and synaptic dysfunctions play a critical role in association with the two well-known molecular agents of the disease, the Aβ1-42 peptide oligomers and the hyperphosphorylated tau protein. Arachidonic acid, the main member of the ω-6 series, is quantitatively the second polyunsaturated fatty acid in brain and is mainly esterified in membrane phospholipids. It is specifically released by the cytosolic phospholipase A2 whose inhibition or gene suppression counteract the deleterious effects of Aβ1-42 peptide oligomers on cognitive abilities. Arachidonic acid can be reincorporated under the action of the acyl-CoA synthetase 4 and lysophospholipid acyltransferases which remain to be characterized. Free arachidonic acid can be involved in Alzheimer’s disease through several mechanisms. First it is converted by cyclooxygenases-1/2 and the specific prostaglandin synthases into PGE2 and PGD2 which contributes to the occurrence and progression of neuroinflammation. Neuroinflammation has positive as well as negative effects, by favoring Aβ1-42 peptide clearance on one hand and by increasing the production of neurotoxic compounds on the other hand. Second, free arachidonic acid is also involved in synaptic functions as a retrograde messenger and as a regulator of neuromediator exocytosis. Third, some studies indicated that free arachidonic acid and its derivatives activate kinases involved in tau hyperphosphorylation. In addition, the dietary intakes of arachidonic acid in western food increased in the last period. Taken together, these various reports support the hypothesis that arachidonic acid is interesting target in nutrition-based preventive strategies against this disease.

DOI: 10.29245/2572.942X/2016/9.1086 View / Download Pdf

Yoshio Matsuda

Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital, Japan

DOI: 10.29245/2572.942X/2016/1.1011 View / Download Pdf

Jeffrey L. Neul1,2, Alan K. Percy2

1Department of Neuroscience, University of California San Diego, USA
2Civitan International Research Center, University of Alabama at Birmingham, USA

DOI: 10.29245/2572.942X/2016/1.1008 View / Download Pdf

Carl Marincowitz and Will Townend

Emergency Department, Hull Royal Infirmary, Anlaby Road, Hull, UK

Background: Head injury represents an extremely common presentation to Emergency Departments (ED), but not all patients present immediately after injury. There is evidence that clinical deterioration following head injury will usually occur within 24 hours. It is unclear whether this means that head injury patients that present in a delayed manner, especially after 24 hours, have a lower prevalence of significant traumatic injuries.

Methods: This is a commentary on a systematic review that we conducted with the aim of identifying all studies that assess the risk of significant injuries in delayed ED presentation head injury populations. We postulated that the risk of injury may be different in this group compared to patients that present immediately.

Results: Three studies were eligible for inclusion. They were all of poor methodological quality, and heterogeneity prevented meta-analysis. The reported prevalence of traumatic intra-cranial injury on CT was between 2.2% and 6.3%.

Conclusion: Available evidence suggests that head injury patients who present in a delayed fashion to the ED may have lower rates of intra-cranial injury compared to non-delayed head injury patients. However, the evidence is sparse and it is of too low quality to guide clinical practice. Further research is required to help the clinical risk assessment of this group.

DOI: 10.29245/2572.942X/2016/1.1006 View / Download Pdf

Kurt A. Jellinger

Institute of Clinical Neurobiology, Vienna, Austria

The aging brain is characterized by the simultaneous presence of multiple pathologies, and the prevalence of multi-morbidity increases with age. Large clinico-pathological correlative studies have shown that in brains of both cognitively intact and impaired aged subjects, the presence of a single disease is a rare finding, while most brains show neurodegenerative, cerebrovascular and other pathologies, which frequently have been missed clinically and may even be difficult to identify at postmortem examination. Since both clinical and autopsy studies differ in selection and classification criteria and in the applied evaluation methods, irrespective of the clinical symptoms, the reported frequency of cerebral pathologies varies considerably. The frequent co-occurrence of different pathologies indicates their mutual interaction in order to promote cognitive decline and other clinical symptoms. These facts have also implications for improvement of clinical diagnosis and prognosis, for the development of specific biomarkers, preventive strategies, and therapeutic targets for cerebral multi-morbidity.

DOI: 10.29245/2572.942X/2016/1.1001 View / Download Pdf