scholarly journals Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 21 ◽  
Author(s):  
David Weise ◽  
Christopher M. Weise ◽  
Markus Naumann
Keyword(s):  
Botulinum Neurotoxin ◽  
Clinical Effect ◽  
Current Evidence ◽  
Sensory Afferents ◽  
Central Effects ◽  
Clinical Observations ◽  
The Central Nervous System ◽  
Clinical Conditions ◽  
The Brain ◽  
Dystonic Disorders

For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT’s pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT’s central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered “side-effects” but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions.

Peptide neurohormones: their role in thermoregulation and fever

1983 ◽  
Vol 61 (7) ◽  
pp. 579-593 ◽  
Author(s):  
W. D. Ruwe ◽  
W. L. Veale ◽  
K. E. Cooper
Keyword(s):  
Body Temperature ◽  
Anterior Commissure ◽  
Extracellular Fluid ◽  
Current Evidence ◽  
Central Administration ◽  
Febrile Response ◽  
Axonal Projections ◽  
The Central Nervous System ◽  
Convulsive Disorders ◽  
The Brain

The neural elements of the rostral diencephalon in the mammal have been implicated in the regulation of body temperature. Moreover, it may be the neural elements within this region of the brain which activate the febrile mechanisms in response to pyrogen. Is it possible that the neuropeptides located within this area of the brain serve as neurochemical intermediaries involved in temperature regulation, fever, and (or) antipyresis? Central administration of several neuropeptides can elicit marked changes in the core temperature of an animal. Although most of these purative neuroregulators exert only a very minor influence on thermoregulation, a small number of the neuropeptides have been shown to have a profound effect on the system controlling this basic vegetative function. One of these peptides, arginine vasopressin (AVP) may play a role as an endogenous antipyretic. The neuroanatomical localization of this peptide, as well as its axonal projections, are consistent with such a role for this neurohypophyseal peptide in the mediation of antipyresis. In addition, current evidence suggests that AVP does function as a neurotransmitter. Examination of the febrile response to pyrogen in both the periparturient animal and the neonate indicates that an elevation in plasma levels of AVP is closely correlated with the diminution in the febrile response. Also, when AVP is perfused into punctate regions of the brain, a pyrogen-induced fever may be markedly suppressed. AVP appears to act primarily within the septal area, 2- to 3-mm rostral to the anterior commissure. During the development of fever, the release of AVP is altered within these same loci. As body temperature decreases during the febrile state, there is a concomitant increase in the amount of AVP released into the extracellular fluid of these septal sites. Very recent findings suggest that AVP may have additional central neurochemical functions. For example, this peptide may be involved in the etiology of some forms of convulsive disorders. The precise manner in which body temperature is regulated by the central nervous system normally and during fever is not well understood. In particular, the central mechanism of action of AVP in these processes remains to be determined. Currently, it is clear that the critical central mechanisms which are active in thermoregulation and fever are quite complex and will require many more years of investigation before the exact role of each can be enunciated.

scholarly journals Perivascular and Perineural Pathways Involved in Brain Delivery and Distribution of Drugs after Intranasal Administration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 598 ◽  
Author(s):  
Jeffrey J. Lochhead ◽  
Thomas P. Davis
Keyword(s):  
Current Evidence ◽  
Perivascular Spaces ◽  
Brain Delivery ◽  
Physiological Conditions ◽  
Routes Of Administration ◽  
Disease States ◽  
Efficient Delivery ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood–brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.

scholarly journals Complex Regional Pain Syndrome. A Comprehensive Review on Neuroplastic Changes Supporting the Use of Non-invasive Neurostimulation in Clinical Settings

2021 ◽  
Vol 2 ◽  
Author(s):  
Andrea Zangrandi ◽  
Fannie Allen Demers ◽  
Cyril Schneider
Keyword(s):  
Complex Regional Pain Syndrome ◽  
Pain Syndrome ◽  
Current Evidence ◽  
Clinical Settings ◽  
Non Invasive ◽  
The Central Nervous System ◽  
Spinal Roots ◽  
Invasive Neurostimulation ◽  
Future Work ◽  
The Brain

Background: Complex regional pain syndrome (CRPS) is a rare debilitating disorder characterized by severe pain affecting one or more limbs. CRPS presents a complex multifactorial physiopathology. The peripheral and sensorimotor abnormalities reflect maladaptive changes of the central nervous system. These changes of volume, connectivity, activation, metabolism, etc., could be the keys to understand chronicization, refractoriness to conventional treatment, and developing more efficient treatments.Objective: This review discusses the use of non-pharmacological, non-invasive neurostimulation techniques in CRPS, with regard to the CRPS physiopathology, brain changes underlying chronicization, conventional approaches to treat CRPS, current evidence, and mechanisms of action of peripheral and brain stimulation.Conclusion: Future work is warranted to foster the evidence of the efficacy of non-invasive neurostimulation in CRPS. It seems that the approach has to be individualized owing to the integrity of the brain and corticospinal function. Non-invasive neurostimulation of the brain or of nerve/muscles/spinal roots, alone or in combination with conventional therapy, represents a fertile ground to develop more efficient approaches for pain management in CRPS.

scholarly journals COVID-19 neurological manifestations: a narrative review on the mechanisms, pathogenesis, and clinical management

2020 ◽  
Vol 9 (12) ◽  
pp. e4291210724
Author(s):  
Letícia Nunes Campos ◽  
Ana Clara Santos Costa ◽  
Débora Dantas Nucci Cerqueira ◽  
Gabriele Rodrigues Rangel ◽  
Isabela Cristina de Farias Andrade ◽  
...  
Keyword(s):  
Nervous System ◽  
Viral Entry ◽  
Wide Spectrum ◽  
Current Evidence ◽  
Neurological Manifestations ◽  
International Data ◽  
The Central Nervous System ◽  
Respiratory Conditions ◽  
The Brain

Coronaviruses are a large viral family, whose infections are recognized since 1960, varying from the common cold to more critical respiratory conditions. Regarding coronavirus 2019 (COVID-19), a wide spectrum of neurological manifestations among infected patients were reported, raising concerns whether Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had tropism for the central nervous system. To clarify these questions, this bibliographic review was carried out by searching for articles based on national and international data during the period from December 2019 to June 2020. Thus, this review summarizes the current evidence on the transmission routes, focusing on the olfactory bulb and the hematogenic pathways, as well as the direct and indirect pathological mechanisms through which SARS-CoV-2 causes neurological damage. Moreover, clinical, laboratorial, and therapeutic aspects to manage patients with COVID-19 related neurological symptoms are outlined. Finally, development of treatments tackling specific structures and pathways related to viral entry and cardiovascular regulation on the brain are expected, in addition to monitoring of patients affected by the COVID-19 to assess long-term consequences on the nervous system.

Current Evidence on the Effect of Dietary Polyphenols Intake on Brain Health

2020 ◽  
Vol 16 (8) ◽  
pp. 1170-1182 ◽  
Author(s):  
Stefania D'Angelo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dietary Intake ◽  
Neurodegenerative Diseases ◽  
Health Benefits ◽  
Current Evidence ◽  
Brain Health ◽  
Dietary Polyphenols ◽  
The Central Nervous System ◽  
The Brain

Background: In recent years, the possibility of favorably influencing the cognitive capacity through the promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship between nutritional habits and brain health has attracted special attention. Polyphenols are secondary metabolites of plants. These phytochemicals are present in vegetables, fruits, legumes, olive oil, nuts. They include several antioxidant compounds and are generally considered to be involved in defense against chronic human diseases. In recent years, there has been a growing scientific interest in their potential health benefits to the brain. Objective: In this mini-review, we focus on the current evidence defining the position of polyphenols dietary intake in the prevention/slowdown of human neurodegenerative diseases. Methods: A literature research was performed using the keywords “polyphenols”, “brain”, “nutrition”, individually or all together, focusing on human trials. Results: The available clinical studies on the effect of polyphenols on cognitive functions are quite convincing. Regular dietary intake of polyphenols would seem to reduce the risk of neurodegenerative diseases. Moreover, beyond their beneficial power on the central nervous system, these phytochemicals seem also to be able to work on numerous cellular targets. They show different biological actions, that however, have to be confirmed in long-term randomized clinical trials. Currently, most data propose that a combination of phytonutrients instead of any single polyphenol is responsible for health benefits. Conclusions: Evolving indications suggest that dietary polyphenols may exercise beneficial actions on the central nervous system, thus representing a possible tool to preserve cognitive performance. Key questions to improve the coherence and reproducibility in the development of polyphenols as a possible future therapeutic drug require a better understanding of the sources of polyphenols, their treatment and more standardized tests including bioavailability of bioactive metabolites and studies of permeability of the brain.

The Effect of Some Drugs on the Electrical Activity of the Brain, and on Behaviour

1954 ◽  
Vol 100 (418) ◽  
pp. 125-128 ◽  
Author(s):  
J. Elkes ◽  
C. Elkes ◽  
P. B. Bradley
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Synaptic Transmission ◽  
Electrical Activity ◽  
Reference Points ◽  
Central Effects ◽  
System Form ◽  
The Central Nervous System ◽  
The Brain

Peripheral neuro-effector sites within and outside the autonomic nervous system form useful reference points for the study of the central effects of some agents. Nevertheless, ready analogies between peripheral neurohumoral mediation, and central synaptic transmission may be grossly misleading, and reliance must solely be placed on data derived from within the central nervous system itself.

scholarly journals Neurological complications and infection mechanism of SARS-COV-2

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dandan Wan ◽  
Tingfu Du ◽  
Weiqi Hong ◽  
Li Chen ◽  
Haiying Que ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Respiratory Diseases ◽  
Neurological Diseases ◽  
Neurological Complications ◽  
Experimental Models ◽  
Current Evidence ◽  
Global Pandemic ◽  
The Central Nervous System ◽  
The Brain

AbstractCurrently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Ultrastructural morphology of neurosecretory neurons in the barnacle Balanus amphitrite

1990 ◽  
Vol 48 (3) ◽  
pp. 434-435
Author(s):  
Grazia Tagliafierro ◽  
Cristiana Crosa ◽  
Marco Canepa ◽  
Tiziano Zanin
Keyword(s):  
Nervous System ◽  
Ultrastructural Level ◽  
Uranyl Acetate ◽  
Balanus Amphitrite ◽  
Neurosecretory Neurons ◽  
The Central Nervous System ◽  
Ultrathin Sections ◽  
Dense Core Granules ◽  
The Brain ◽  
Ocellar Nerve

Barnacles are very specialized Crustacea, with strongly reduced head and abdomen. Their nervous system is rather simple: the brain or supra-oesophageal ganglion (SG) is a small bilobed structure and the toracic ganglia are fused into a single ventral mass, the suboesophageal ganglion (VG). Neurosecretion was shown in barnacle nervous system by histochemical methods and numerous putative hormonal substances were extracted and tested. Recently six different types of dense-core granules were visualized in the median ocellar nerve of Balanus hameri and serotonin and FMRF-amide like substances were immunocytochemically detected in the nervous system of Balanus amphitrite. The aim of the present work is to localize and characterize at ultrastructural level, neurosecretory neuron cell bodies in the VG of Balanus amphitrite.Specimens of Balanus amphitrite were collected in the port of Genova. The central nervous system were Karnovsky fixed, osmium postfixed, ethanol dehydrated and Durcupan ACM embedded. Ultrathin sections were stained with uranyl acetate and lead citrate. Ultrastructural observations were made on a Philips M 202 and Zeiss 109 T electron microscopy.

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