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Frontiers in Neurology 2019The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous... (Review)
Review
The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Sensory fibers can be assessed using quantitative sensory test. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity.
PubMed: 31551921
DOI: 10.3389/fneur.2019.00970 -
IBRO Neuroscience Reports Dec 2022Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to...
Alcoholic neuropathy (AN), a debilitating condition that mainly affects chronic alcohol drinkers, is thought to cause lesions in the peripheral nervous system leading to sensory, autonomic, and motor dysfunctions. Despite many studies, the pathogenesis of these lesions is still not completely understood. We investigated few aspects on the development of alcohol-induced peripheral neuropathy, by assessing sensory, motor and autonomic functions, as well as stereological analysis of axonal fibers and myelin sheath of the sciatic nerve. Twelve male Wistar rats were divided into Control group and Alcohol group that was submitted to Two Bottle-Choice Paradigm of intermittent and voluntary alcohol solution intake (20%; v/v) during eight weeks. At the end of treatment, three different sensorium-motor tests were applied - Tactile Sensitivity, Thermal Sensitivity, and Functional Observational Battery (FOB). Quantitative morphometric analysis of sciatic nerve structures was performed by stereological method. Alcohol concentration in the blood was measured to analyze possible correlation between availability of alcohol in the blood and the magnitude of the peripheral nerve lesion. Our data showed a peripheral effect of chronic alcohol intake associated with hyperalgesia and a process of demyelination with a strong correlation with alcohol consumption. This process was associated with increased tactile sensitivity, with behavioral reflexes such as locomotor hyperactivity, changes in gait and balance, and autonomic reflexes such as piloerection.
PubMed: 36065406
DOI: 10.1016/j.ibneur.2022.08.004 -
Acta Medica (Hradec Kralove) 2022Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects....
Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects. The aim of the study was to analyse the clinical signs of acute paraoxon poisoning in rats and to determine the relationship between the intensity of signs of poisoning and the dose of paraoxon and/or the outcome of poisoning in rats. Animals were treated with either saline or atropine (10 mg/kg intramuscularly). The median subcutaneous lethal dose (LD50) of paraoxon was 0.33 mg/kg and protective ratio of atropine was 2.73. The presence and intensity of signs of poisoning in rats (dyspnoea, lacrimation, exophthalmos, fasciculations, tremor, ataxia, seizures, piloerection, stereotypic movements) were observed and recorded for 4 h after the injection of paraoxon. Intensity of these toxic phenomena was evaluated as: 0 - absent, 1 - mild/moderate, 2 - severe. Fasciculations, seizures and tremor were more intense at higher doses of paraoxon and in non-survivors. In unprotected rats piloerection occurred more often and was more intense at higher doses of paraoxon as well as in non-survivors. In atropine-protected rats, piloerection did not correlate with paraoxon dose or outcome of poisoning. The intensity of fasciculations and seizures were very strong prognostic parameters of the poisoning severity.
Topics: Acetylcholinesterase; Animals; Atropine; Fasciculation; Paraoxon; Rats; Seizures; Tremor
PubMed: 35793503
DOI: 10.14712/18059694.2022.10 -
Frontiers in Neurology 2022Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another...
INTRODUCTION
Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another possible cause of recurrent seizures in the elderly, and may account for a proportion of cases of LOE of unknown origin (LOEUO). This 24-h ambulatory electroencephalography (AEEG)-based study compared patients with LOEUO and AE to identify features suggestive of immune-mediated seizures in the elderly.
MATERIALS AND METHODS
We retrospectively reviewed 232 AEEG examinations performed in patients over 55 years with ≥6-month follow-up, and selected 21 subjects with AE and 25 subjects with LOEUO. Clinical charts and AEEG recordings were carefully analyzed.
RESULTS
Twenty-five patients with LOEUO (12 women, mean age at onset 67.9 years) and 21 AE subjects (8 women, mean age at onset 65.7 years) were enrolled. High-frequency seizures were reported in 20/21 AE and 7/25 LOEUO cases ( < 0.00001). Focal aware seizures were more common in AE (14/21 vs. 6/25, = 0.00058), whereas "isolated" focal-to-bilateral tonic-clonic seizures occurred in 5/25 patients with LOEUO only ( = 0.053). AE subjects reported ictal autonomic manifestations more frequently ( = 0.0033). Three-hundred-seventy and 24 seizures were recorded in 13/21 patients with AE and 3/25 patients with LOEUO, respectively ( = 0.0006). Interictal epileptiform discharges were observed in 70% of both groups, but their sleep activation was more common in AE ( = 0.06).
CONCLUSION
Our study shows that high-frequency focal seizures with autonomic manifestations should raise the suspicion of AE in the elderly with new-onset seizures. It also highlights the relevant contribution of AEEG, which might reduce the diagnostic delay and provide useful clues to recognize AE.
PubMed: 36034285
DOI: 10.3389/fneur.2022.924859 -
ALTEX 2021Animal testing for toxicity assessment of chemicals and pharmaceuticals must take the 3R principles into consideration. During toxicity testing in vivo, clinical signs...
Animal testing for toxicity assessment of chemicals and pharmaceuticals must take the 3R principles into consideration. During toxicity testing in vivo, clinical signs are used to monitor animal welfare and to inform about potential toxicity. This study investigated possible associations between clinical signs, body weight change and histopathological findings observed after necropsy. We hypothesized that clinical signs and body weight loss observed during experiments could be used as early markers of organ toxicity. This represents a potential for refinement in terms of improved study management and decreasing of pain and distress experienced during animal experiments. Data from three sequential toxicity studies of an anti-cancer drug candidate in rats were analyzed using the multivariate partial least squares (PLS) regression method. Associations with a predictive value over 80% were found between the occurrence of mild to severe clinical signs and histopathological findings in the thymus, testes, epididymides and bone marrow. Piloerection, eyes half shut and slightly decreased motor activity were most strongly associated with the pathological findings. A 5% body weight loss was found to be a strong empirical predictor of pathological findings but could also be predicted accurately by clinical signs. Thus, we suggest using mild clinical signs and a 5% body weight loss as toxicity markers and as a non-invasive surveillance tool to monitor research animal welfare in toxicity testing. These clinical signs may also enable reduction of animal use due to their informative potential to support scientific decisions regarding drug candidate selection, dose setting, study design, and toxicity assessment.
Topics: Animal Experimentation; Animal Welfare; Animals; Rats; Toxicity Tests
PubMed: 33118607
DOI: 10.14573/altex.2003311 -
CNS Neuroscience & Therapeutics Sep 2023Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP...
OBJECTIVES
Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP.
METHODS
Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected).
RESULTS
Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP.
CONCLUSIONS
Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.
Topics: Humans; Seizures; Encephalitis; Autoantibodies; Autoimmune Diseases of the Nervous System
PubMed: 36971194
DOI: 10.1111/cns.14192 -
Biomedicines Dec 2022To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate...
To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched and black garlic extracts as adjuvants in the management of sepsis. An experimental in vivo study was carried out with male Sprague-Dawley rats. Animals were randomized in four treatment groups: antibiotic (ceftriaxone) treatment (group I), ceftriaxone plus thiosulfinate-enriched extract (TASE, group II), ceftriaxone plus thiosulfinate-enriched extract and black garlic extracts (TASE + BGE, group III), and ceftriaxone plus black garlic extract (BGE, group IV). All animals were housed and inoculated with 1 × 10 CFU/15 mL of intraperitoneal ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in rats receiving garlic extracts in weight (groups II and III), ocular secretions, and piloerection (group IV). Moreover, less liver edema, vacuolization, and inflammation were observed in groups receiving adjuvant support (groups II, III, and IV). When comparing interleukins 24 h after bacteria inoculum, we found statistically significant differences in TNF-alpha levels in groups receiving BGE (groups III and IV, ≤ 0.05). Blood and peritoneal liquid cultures were also analyzed, and we detected a certain level of in peritoneal cultures from all treatment groups and less bacteria presence in blood cultures in rats receiving garlic extracts (groups II, III, and IV). In conclusion, TASE and BGE could be promising nutraceutical or medicinal agents as coadjuvants in the treatment of sepsis because of its effects in modulating the inflammatory response.
PubMed: 36551850
DOI: 10.3390/biomedicines10123095 -
Toxicology Reports 2018A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5...
A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.
PubMed: 29854612
DOI: 10.1016/j.toxrep.2018.02.012 -
Veterinary Sciences May 2022Thermoregulation in newborn mammals is an essential species-specific mechanism of the nervous system that contributes to their survival during the first hours and days... (Review)
Review
Thermoregulation in newborn mammals is an essential species-specific mechanism of the nervous system that contributes to their survival during the first hours and days of their life. When exposed to cold weather, which is a risk factor associated with mortality in neonates, pathways such as the hypothalamic-pituitary-adrenal axis (HPA) are activated to achieve temperature control, increasing the circulating levels of catecholamine and cortisol. Consequently, alterations in blood circulation and mechanisms to produce or to retain heat (e.g., vasoconstriction, piloerection, shivering, brown adipocyte tissue activation, and huddling) begin to prevent hypothermia. This study aimed to discuss the mechanisms of thermoregulation in newborn domestic mammals, highlighting the differences between altricial and precocial species. The processes that employ brown adipocyte tissue, shivering, thermoregulatory behaviors, and dermal vasomotor control will be analyzed to understand the physiology and the importance of implementing techniques to promote thermoregulation and survival in the critical post-birth period of mammals. Also, infrared thermography as a helpful method to perform thermal measurements without animal interactions does not affect these parameters.
PubMed: 35622774
DOI: 10.3390/vetsci9050246 -
Cell Aug 2020In the skin, sympathetic nerves, arrector pili muscles, and hair follicles form a tri-lineage unit to cause piloerection or goosebumps. In this issue of Cell, Schwartz...
In the skin, sympathetic nerves, arrector pili muscles, and hair follicles form a tri-lineage unit to cause piloerection or goosebumps. In this issue of Cell, Schwartz et al. report that, beyond goosebumps, muscle-anchored nerves form "synapse-like" connections with hair follicle stem cells to promote hair regeneration in response to cold.
Topics: Hair; Hair Follicle; Muscle, Smooth; Piloerection; Stem Cells
PubMed: 32763185
DOI: 10.1016/j.cell.2020.07.004