The significance of the detection of oxidative and reducing tissue enzymes for questions of localization in the brain

1927 ◽  
Vol 23 (6-7) ◽  
pp. 613-621
Author(s):  
М. Bielschowsky ◽  
М. Rose
Keyword(s):  
Nervous System ◽  
The Right ◽  
The Brain

Histology of the nervous system is served, for the purpose of research, almost exclusively by stained slices from fixed objects. As fixing agents, mainly alcohol, formaldehyde and mixtures of chromium salts are used, which produce more or less fast clotting of tissue colloids, as a result of which the in vivo structure of cells with their processes is very much changed. To what extent our preparations give us the right to conclude about the living structure of cells and especially about the processes running or already running intra vitam is an old and much debated problem.

ASSESSMENT OF PHYSIOLOGICAL PARAMETERS OF THE TRIGEMINAL AND COCHLEOVESTIBULAR SYSTEMS IN TEMPOROMANDIBULAR JOINT PAIN DYSFUNCTION

2020 ◽  
Vol 17 (2) ◽  
pp. 110-120
Author(s):  
N.D. Sorokina ◽  
◽  
L.R. Shahalieva ◽  
S.S. Pertsov ◽  
L.V. Polma ◽  
...  
Keyword(s):  
Nervous System ◽  
Evoked Potentials ◽  
Temporomandibular Joint ◽  
Differential Diagnostics ◽  
Autonomous Nervous System ◽  
Dental Diseases ◽  
Grade Ii ◽  
The Right ◽  
Distal Occlusion ◽  
The Brain

One of the most common causes of chronic pain in the facial region, including in the trigeminal nerve link, which is not associated with dental diseases, is pain dysfunction of the temporomandibular joint. At the same time, there is evidence in the literature that there are relationships between pain dysfunction of the temporomandibular joint, abnormal occlusion, cervical-muscular tonic phenomena, postural disorders, dysfunction of the Autonomous nervous system and cochleovestibular manifestations. At the same time, neurophysiological indicators of functional disorders in the maxillofacial region and intersystem interactions in pain dysfunction of the temporomandibular joint are insufficiently studied.Goal. The aim of the work is to evaluate the neurophysiological features of trigeminal afferentation in terms of trigeminal somatosensory evoked potentials (TSWP) and the auditory conducting system of the brain in terms of acoustic stem evoked potentials (ASVP) in distal occlusion of the dentition with pain dysfunction of the temporomandibular joint (TMJ) in comparison with physiological occlusion in students 18-21 years old. Material and methods. The main study included 41 students with distal occlusion (21 girls and 20 boys), (grade II Engl, symmetrically right and left in 14 people, and grade II Engl on the left and grade I on the right in 12 people, grade I on the left and grade II on the right in 15 people). All respondents with distal occlusion and who were practically healthy signed an informed consent to participate in the study. We used complex orthodontic methods of examination, subjective degree of severity and intensity of pain in the TMJ, assessment of the Autonomous nervous system (samples and tests), and neurophysiological methods for assessing TSVP and ASVP. Results. Significant differences in ASEP parameters were found in the group of respondents with distal occlusion in the form of a decrease in the latency period of peak I, III, and V compared to physiological occlusion, that correlated with the subjective assessment (in points) of cochleovestibular disorders. According to the TSVP study, a decrease in the duration of latent periods was found, which indicates an increased excitability of non-specific brain stem structures at the medullo-ponto-mesencephalic level compared to the control group. Conclusions. The results obtained are supposed to be used for differential diagnostics, including such dental diseases as TMJ pain dysfunction, occlusion abnormalities accompanied by pain syndrome. Additional functional diagnostics of multi-modal VP of the brain (acoustic evoked potentials, trigeminal evoked potentials) can be performed in conjunction with indicators of autonomic nervous system dysfunction, with parameters of severity of clinical symptoms of cochleovestibular disorders, musculoskeletal dysfunction the maxillofacial area, with indicators of pain, which will determine the tactics and effectiveness of subsequent treatment.

scholarly journals A conducting polymer with enhanced electronic stability applied in cardiac models

2016 ◽  
Vol 2 (11) ◽  
pp. e1601007 ◽  
Author(s):  
Damia Mawad ◽  
Catherine Mansfield ◽  
Antonio Lauto ◽  
Filippo Perbellini ◽  
Geoffrey W. Nelson ◽  
...  
Keyword(s):  
Nervous System ◽  
Beneficial Effect ◽  
Phytic Acid ◽  
Ex Vivo ◽  
Chitosan Film ◽  
In Vivo Experiments ◽  
Conductive System ◽  
The Brain ◽  
Operational Time

Electrically active constructs can have a beneficial effect on electroresponsive tissues, such as the brain, heart, and nervous system. Conducting polymers (CPs) are being considered as components of these constructs because of their intrinsic electroactive and flexible nature. However, their clinical application has been largely hampered by their short operational time due to a decrease in their electronic properties. We show that, by immobilizing the dopant in the conductive scaffold, we can prevent its electric deterioration. We grew polyaniline (PANI) doped with phytic acid on the surface of a chitosan film. The strong chelation between phytic acid and chitosan led to a conductive patch with retained electroactivity, low surface resistivity (35.85 ± 9.40 kilohms per square), and oxidized form after 2 weeks of incubation in physiological medium. Ex vivo experiments revealed that the conductive nature of the patch has an immediate effect on the electrophysiology of the heart. Preliminary in vivo experiments showed that the conductive patch does not induce proarrhythmogenic activities in the heart. Our findings set the foundation for the design of electronically stable CP-based scaffolds. This provides a robust conductive system that could be used at the interface with electroresponsive tissue to better understand the interaction and effect of these materials on the electrophysiology of these tissues.

scholarly journals Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1542
Author(s):  
Felix Neumaier ◽  
Boris D. Zlatopolskiy ◽  
Bernd Neumaier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Model Systems ◽  
Pharmacokinetic Parameters ◽  
Special Focus ◽  
Drug Penetration ◽  
The Central Nervous System ◽  
The Brain

Delivery of most drugs into the central nervous system (CNS) is restricted by the blood–brain barrier (BBB), which remains a significant bottleneck for development of novel CNS-targeted therapeutics or molecular tracers for neuroimaging. Consistent failure to reliably predict drug efficiency based on single measures for the rate or extent of brain penetration has led to the emergence of a more holistic framework that integrates data from various in vivo, in situ and in vitro assays to obtain a comprehensive description of drug delivery to and distribution within the brain. Coupled with ongoing development of suitable in vitro BBB models, this integrated approach promises to reduce the incidence of costly late-stage failures in CNS drug development, and could help to overcome some of the technical, economic and ethical issues associated with in vivo studies in animal models. Here, we provide an overview of BBB structure and function in vivo, and a summary of the pharmacokinetic parameters that can be used to determine and predict the rate and extent of drug penetration into the brain. We also review different in vitro models with regard to their inherent shortcomings and potential usefulness for development of fast-acting drugs or neurotracers labeled with short-lived radionuclides. In this regard, a special focus has been set on those systems that are sufficiently well established to be used in laboratories without significant bioengineering expertise.

scholarly journals Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

1994 ◽  
Vol 5 (5) ◽  
pp. 304-311 ◽  
Author(s):  
K. J. Doshi ◽  
F. D. Boudinot ◽  
J. M. Gallo ◽  
R. F. Schinazi ◽  
C. K. Chu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Brain Targeting ◽  
The Central Nervous System ◽  
Intravenous And Oral Administration ◽  
The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

Triopia: Craniofacial Malformation with Prosencephalic Duplication

1995 ◽  
Vol 32 (4) ◽  
pp. 334-345
Author(s):  
Eric J. Stelnicki ◽  
Jeffrey L. Marsh ◽  
Thomas A. Woolsey ◽  
Benjamin Chee Ping Lee ◽  
Michael J. Noetzel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Medical Imaging ◽  
Cerebral Hemisphere ◽  
Computer Assisted ◽  
Hard Tissue ◽  
Craniofacial Malformation ◽  
The Right ◽  
Central Nervous System Anomalies

A case of ocular duplication with complex craniofacial and central nervous system anomalies is described. The anomaly is termed triopia because the child's most overt and distinguishing feature was three eyes: the left orbit contained two globes with independent ocular adnexa; the right orbit contained one normal appearing and functioning globe. Computer assisted medical imaging was used to define, in vivo, the intra- and extracranial soft and hard tissue anomalies: the cerebral hemisphere ipsilateral to the ocular duplication was also duplicated. Possible bases for this anomaly include duplication of primordia for the eye and secondary prosencephalon.

scholarly journals Infectious Herpes Simplex Virus in the Brain Stem Is Correlated with Reactivation in the Trigeminal Ganglia

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Jessica R. Doll ◽  
Richard L. Thompson ◽  
Nancy M. Sawtell
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Brain Stem ◽  
Infectious Virus ◽  
Trigeminal Ganglia ◽  
Latently Infected ◽  
Simplex Virus ◽  
The Brain

ABSTRACTHerpes simplex virus (HSV) establishes latency in neurons of the peripheral and central nervous systems (CNS). Evidence is mounting that HSV latency and reactivation in the nervous system has the potential to promote neurodegenerative processes. Understanding how this occurs is an important human health goal. In the mouse model,in vivoviral reactivation in the peripheral nervous system, triggered by hyperthermic stress, has been well characterized with respect to frequency and cell type. However, characterization ofin vivoreactivation in the CNS is extremely limited. Further, it remains unclear whether virus reactivated in the peripheral nervous system is transported to the CNS in an infectious form, how often this occurs, and what parameters underlie the efficiency and outcomes of this process. In this study, reactivation was quantified in the trigeminal ganglia (TG) and the brain stem from the same latently infected animal using direct assays of equivalent sensitivity. Reactivation was detected more frequently in the TG than in the brain stem and, in all but one case, the amount of virus recovered was greater in the TG than that detected in the brain stem. Viral protein positive neurons were observed in the TG, but a cellular source for reactivation in the brain stem was not identified, despite serially sectioning and examining the entire tissue (0/6 brain stems). These findings suggest that infectious virus detected in the brain stem is primarily the result of transport of reactivated virus from the TG into the brain stem.IMPORTANCELatent herpes simplex virus (HSV) DNA has been detected in the central nervous systems (CNS) of humans postmortem, and infection with HSV has been correlated with the development of neurodegenerative diseases. However, whether HSV can directly reactivate in the CNS and/or infectious virus can be transported to the CNS following reactivation in peripheral ganglia has been unclear. In this study, infectious virus was recovered from both the trigeminal ganglia and the brain stem of latently infected mice following a reactivation stimulus, but a higher frequency of reactivation and increased titers of infectious virus were recovered from the trigeminal ganglia. Viral proteins were detected in neurons of the trigeminal ganglia, but a cellular source of infectious virus could not be identified in the brain stem. These results suggest that infectious virus is transported from the ganglia to the CNS following reactivation but do not exclude the potential for direct reactivation in the CNS.

scholarly journals Coordinated Regulation and Widespread Cellular Expression of Interferon-Stimulated Genes (ISG) ISG-49, ISG-54, and ISG-56 in the Central Nervous System after Infection with Distinct Viruses

2006 ◽  
Vol 81 (2) ◽  
pp. 860-871 ◽  
Author(s):  
Christie Wacher ◽  
Marcus Müller ◽  
Markus J. Hofer ◽  
Daniel R. Getts ◽  
Regina Zabaras ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dominant Role ◽  
Lymphocytic Choriomeningitis ◽  
Wild Type ◽  
Cellular Expression ◽  
The Central Nervous System ◽  
The Brain ◽  
Lcmv Infection

ABSTRACT The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.

scholarly journals Heterogeneous incidence and propagation of spreading depolarizations

2016 ◽  
Vol 37 (5) ◽  
pp. 1748-1762 ◽  
Author(s):  
Dan Kaufmann ◽  
Jeremy J Theriot ◽  
Jekaterina Zyuzin ◽  
C Austin Service ◽  
Joshua C Chang ◽  
...  
Keyword(s):  
Nervous System ◽  
Great Variability ◽  
Neurologic Disease ◽  
Neurologic Diseases ◽  
Present Evidence ◽  
System Activity ◽  
Nervous System Activity ◽  
The Brain

Spreading depolarizations are implicated in a diverse set of neurologic diseases. They are unusual forms of nervous system activity in that they propagate very slowly and approximately concentrically, apparently not respecting the anatomic, synaptic, functional, or vascular architecture of the brain. However, there is evidence that spreading depolarizations are not truly concentric, isotropic, or homogeneous, either in space or in time. Here we present evidence from KCl-induced spreading depolarizations, in mouse and rat, in vivo and in vitro, showing the great variability that these depolarizations can exhibit. This variability can help inform the mechanistic understanding of spreading depolarizations, and it has implications for their phenomenology in neurologic disease.

scholarly journals Clinical Trials for Gene Therapy in Lysosomal Diseases With CNS Involvement

2021 ◽  
Vol 8 ◽  
Author(s):  
Caroline Sevin ◽  
Kumaran Deiva
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Ex Vivo ◽  
Central Nervous System Involvement ◽  
Large Animal ◽  
Hematopoietic Stem ◽  
The Brain

There are over 70 known lysosomal storage disorders (LSDs), most caused by mutations in genes encoding lysosomal hydrolases. Central nervous system involvement is a hallmark of the majority of LSDs and, if present, generally determines the prognosis of the disease. Nonetheless, brain disease is currently poorly targeted by available therapies, including systemic enzyme replacement therapy, mostly (but not only) due to the presence of the blood–brain barrier that restricts the access of orally or parenterally administered large molecules into the brain. Thus, one of the greatest and most exciting challenges over coming years will be to succeed in developing effective therapies for the treatment of central nervous system manifestations in LSDs. Over recent years, gene therapy (GT) has emerged as a promising therapeutic strategy for a variety of inherited neurodegenerative diseases. In LSDs, the ability of genetically corrected cells to cross-correct adjacent lysosomal enzyme-deficient cells in the brain after gene transfer might enhance the diffusion of the recombinant enzyme, making this group of diseases a strong candidate for such an approach. Both in vivo (using the administration of recombinant adeno-associated viral vectors) and ex vivo (auto-transplantation of lentiviral vector-modified hematopoietic stem cells-HSCs) strategies are feasible. Promising results have been obtained in an ever-increasing number of preclinical studies in rodents and large animal models of LSDs, and these give great hope of GT successfully correcting neurological defects, once translated to clinical practice. We are now at the stage of treating patients, and various clinical trials are underway, to assess the safety and efficacy of in vivo and ex vivo GT in several neuropathic LSDs. In this review, we summarize different approaches being developed and review the current clinical trials related to neuropathic LSDs, their results (if any), and their limitations. We will also discuss the pitfalls and the remaining challenges.

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