scholarly journals High-Dose Immunoglobulin G Suppresses Local Inflammatory Reaction and Facilitates Functional Recovery Following Olfactory System Injury

2021 ◽  
Author(s):  
Masayoshi Kobayashi ◽  
Kohei Nishida ◽  
Eisuke Ishigami ◽  
Kazuhiko Takeuchi
Keyword(s):  
Functional Recovery ◽  
Immunoglobulin G ◽  
Head Injuries ◽  
Olfactory Nerve ◽  
Nerve Fibers ◽  
Olfactory Dysfunction ◽  
High Dose ◽  
Behavioral Test ◽  
Local Inflammatory Reaction ◽  
Injury Models

Abstract BackgroundHead trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti-inflammatory treatment using steroids or anti-cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high-dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. MethodsOlfactory nerve transection (NTx) was performed in OMP-tau-lacZ mice to establish injury models. High-dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42 and 100 days after the drug injection. X-gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test.ResultsHigh-dose IgG-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG-injected mice. ConclusionsThese findings suggest that high-dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.

scholarly journals Acute systemic experimental inflammation does not reduce human odor identification performance

2021 ◽  
Author(s):  
A Tognetti ◽  
G Sarolidou ◽  
J Lasselin ◽  
M Lekander ◽  
M J Olsson ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Inflammatory Diseases ◽  
Placebo Treatment ◽  
Olfactory Dysfunction ◽  
High Dose ◽  
Common Symptom ◽  
Identification Performance ◽  
Double Blind ◽  
Olfactory Identification ◽  
Factor Α

Abstract Olfactory dysfunction is a common symptom of various diseases but the underlying pathophysiology has not been fully understood. Evidence from both animal and human studies suggests that local inflammation of the olfactory epithelium is linked to olfactory dysfunction. However, whether systemic inflammation causes olfactory dysfunction is yet to be determined. In the present behavioral study, we set out to test whether acute systemic inflammation impairs olfactory identification performance by inducing a transient and controlled state of systemic inflammation using an experimental endotoxemia model. We treated young, otherwise healthy, participants (N=20) with a relatively high dose (2.0 ng/kg) of lipopolysaccharide (LPS) and a placebo treatment in a double-blind within-subject design, and assessed participants’ ability to identify odors using the MONEX-40, a reliable method for experimental assessment of odor ID ability in healthy and young individuals. Our results show that olfactory identification performance was not affected by the acute systemic inflammation triggered by the injection of LPS. Moreover, no associations were found between the change of olfactory performance followed by LPS injection and levels of circulating pro-inflammatory cytokines (interleukin-6, interleukin-8, and tumor necrosis factor-α). Because experimental LPS-induced systemic inflammation does not affect olfactory identification performance, our findings suggest that chronic, rather than transient, systemic inflammation is a more likely mechanism to explore in order to explain the olfactory deficits observed in inflammatory diseases.

Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia

2020 ◽  
pp. 1-6
Author(s):  
Masuho Saburi ◽  
Masao Ogata ◽  
Yasuhiro Soga ◽  
Takako Satou ◽  
Kazuhito Itani ◽  
...  
Keyword(s):  
Corticosteroid Therapy ◽  
Immunoglobulin G ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
First Line ◽  
Laboratory Findings ◽  
Platelet Production ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immature Platelet Fraction

<b><i>Objective:</i></b> Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. <b><i>Methods:</i></b> Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. <b><i>Results:</i></b> Median PA-IgG was 285 ng/10<sup>7</sup> cells (range, 45.5–18,200 ng/10<sup>7</sup> cells), and median IPF was 15.5% (range, 5.4–62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0–46 ng/10<sup>7</sup> cells; IPF, 1.1–9.5%). First-line therapy was performed using standard-dose prednisolone (0.5–1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125–1,000 mg/day, 3–4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (<i>p</i> = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4–41.5%) and nonresponders (16.7%; range, 6.3–62.1%; <i>p</i> = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/10<sup>7</sup> cells; range, 101–18,200 ng/10<sup>7</sup> cells) than among responders (254.5 ng/10<sup>7</sup> cells; range, 45.5–470 ng/10<sup>7</sup> cells; <i>p</i> = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000–1.010; <i>p</i> = 0.029). <b><i>Conclusion:</i></b> Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

Height of aneurysm neck and estimated extent of brain retraction: powerful predictors of olfactory dysfunction after surgery for unruptured anterior communicating artery aneurysms

2016 ◽  
Vol 124 (3) ◽  
pp. 720-725 ◽  
Author(s):  
Jaechan Park ◽  
Wonsoo Son ◽  
Duck-Ho Goh ◽  
Dong-Hun Kang ◽  
Joomi Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Significant Risk ◽  
Office Visit ◽  
Olfactory Nerve ◽  
Olfactory Dysfunction ◽  
Maximum Diameter ◽  
Anterior Communicating Artery ◽  
Aneurysm Surgery ◽  
Aneurysm Neck ◽  
Brain Retraction

OBJECT The highest incidence of olfactory dysfunction following a pterional approach and its modifications for an intracranial aneurysm has been reported in cases of anterior communicating artery (ACoA) aneurysms. The radiological characteristics of unruptured ACoA aneurysms affecting the extent of retraction of the frontal lobe and olfactory nerve were investigated as risk factors for postoperative olfactory dysfunction. METHODS A total of 102 patients who underwent a pterional or superciliary keyhole approach to clip an unruptured ACoA aneurysm from 2006 to 2013 were included in this study. Those patients who complained of permanent olfactory dysfunction after their aneurysm surgery, during a postoperative office visit or a telephone interview, were invited to undergo an olfactory test, the Korean version of the Sniffin’ Sticks test. In addition, the angiographic characteristics of ACoA aneurysms, including the maximum diameter, the projecting direction of the aneurysm, and the height of the neck of the aneurysm, were all recorded based on digital subtraction angiography and sagittal brain images reconstructed using CT angiography. Furthermore, the extent of the brain retraction was estimated based on the height of the ACoA aneurysm neck. RESULTS Eleven patients (10.8%) exhibited objective olfactory dysfunction in the Sniffin’ Sticks test, among whom 9 were anosmic and 2 were hyposmic. Univariate and multivariate analyses revealed that the direction of the ACoA aneurysm, ACoA aneurysm neck height, and estimated extent of brain retraction were statistically significant risk factors for postoperative olfactory dysfunction. Based on a receiver operating characteristic (ROC) analysis, an ACoA aneurysm neck height > 9 mm and estimated brain retraction > 12 mm were chosen as the optimal cutoff values for differentiating anosmic/hyposmic from normosmic patients. The values for the area under the ROC curves were 0.939 and 0.961, respectively. CONCLUSIONS In cases of unruptured ACoA aneurysm surgery, the height of the aneurysm neck and the estimated extent of brain retraction were both found to be powerful predictors of the occurrence of postoperative olfactory dysfunction.

scholarly journals Steroids for delayed cerebral edema after traumatic brain injury

2021 ◽  
Vol 12 ◽  
pp. 46
Author(s):  
G. Lakshmi Prasad
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Cerebral Edema ◽  
Head Injuries ◽  
Experimental Studies ◽  
Symptomatic Improvement ◽  
High Dose ◽  
The Mean ◽  
Key Aspects

Background: Brain edema is a common phenomenon after traumatic brain injury (TBI) resulting in increased intracranial pressure and subsequent neurological deterioration. Experimental studies have proven that brain edema is biphasic (cytotoxic followed by vasogenic). Till date, all studies, including the corticosteroid randomization after significant head injury (HI) trial, have used high-dose steroids in the acute period during which the edema is essentially cytotoxic in nature. No clinical data exist pertaining to delayed cerebral edema (vasogenic) and steroids. Methods: Patients who had received steroids for delayed cerebral edema after TBI were retrospectively analyzed over a 2-year period. Steroid dose, timing of steroid prescription, time to improvement of symptoms, and complications were noted. Results: There were six males and three females. Mean age was 41.1 years. There were no severe HI cases. All subjects had cerebral contusions on imaging. Dexamethasone was the preferred steroid starting with 12 mg/day and tapered in 5–7 days. The mean interval to steroid administration after trauma was 7 days. The mean duration of steroid prescription was 6.3 days. All patients had complete symptomatic improvement. The mean time to symptom resolution was 3.8 days. No patients experienced any complications pertinent to steroid usage. Conclusion: This is the first study to document efficacy of steroids for delayed cerebral edema after TBI, at least in mild/moderate head injuries. The timing of steroid usage and dose of steroids is key aspects that might determine its efficacy in TBI which was the drawbacks of the previous studies. Future prospective trials with the above factors in consideration may confirm/refute above findings.

Degeneration and Regrowth of Adrenergic Nerve Fibers in the Rat Peripheral Tissues after 6-Hydroxydopamine

1971 ◽  
Vol 49 (4) ◽  
pp. 345-355 ◽  
Author(s):  
J. de Champlain
Keyword(s):  
Ganglion Cells ◽  
Adrenergic Innervation ◽  
Nerve Fibers ◽  
Adrenergic Nerve ◽  
High Dose ◽  
Rat Tissues ◽  
Peripheral Tissues ◽  
Endogenous Noradrenaline ◽  
6 Hydroxydopamine ◽  
Noradrenaline Levels

Histofluorescent and biochemical changes in the adrenergic nervous system were followed up in rat tissues after one single intravenous injection of a high dose of 100 mg/kg of 6-hydroxydopamine (6-OH-DA). This treatment results in the rapid disappearance of terminal and preterminal fibers in the iris, atria, and small arteries of rats, whereas endogenous noradrenaline pools of the heart are 95% depleted. The capacity of the adrenergic nerve to take up and accumulate tritiated noradrenaline is reduced proportionally to the reduction in endogenous noradrenaline levels. These changes are compatible with the concept of a complete sympathectomy induced by the specific toxic action of 6-OH-DA on the adrenergic fibers. This sympathectomy is not permanent, however, and numerous bundles of preterminal fibers start to grow in the iris and atria within 4 to 5 days following injection. Progressively, in the following weeks, these fibers distribute over the whole organ and give birth to terminal fibers which form a new adrenergic plexus in these tissues. A completely normal innervation is restored 2 to 3 months after administration of 6-OH-DA. The endogenous noradrenaline levels rise progressively in parallel to the development of the new plexus of fibers. Since a complete regeneration of the adrenergic innervation can be demonstrated in the weeks following injection of 6-OH-DA, it appears that this compound can selectively destroy the adrenergic terminal and preterminal fibers without causing a degeneration of the adrenergic ganglion cells.

Autoimmune Peripheral Nervous System Hyperexcitability

2021 ◽  
pp. 138-139
Author(s):  
Christopher J. Klein
Keyword(s):  
Potassium Channel ◽  
Intravenous Immunoglobulin ◽  
Immunoglobulin G ◽  
High Dose ◽  
Voltage Gated ◽  
Idiopathic Pain ◽  
Upper And Lower Extremities ◽  
History Of ◽  
Reflex Testing ◽  
Radioimmunoprecipitation Assay

A 25-year-old man was seen for assessment of progressive pain. He had a distant history of Guillain-Barré syndrome at age 8 years, at which time he had symmetrical proximal and distal weakness of the upper and lower extremities with loss of ambulation. No facial weakness, dysarthria, dysphagia, ptosis, diplopia, or respiratory weakness occurred. At his initial evaluation there was touch hypersensitivity of the muscles and skin. He had no weakness or cognitive involvement, although the pain made it difficult for him to concentrate. His creatine kinase value improved with hydration, but pain and muscle twitching persisted. On examination, he had diffuse extremity and truncal fasciculations and myokymia and reported pain in not only the areas of twitching but also other areas of his extremities and trunk. On neurophysiologic testing, fibular and tibial motor compound muscle action potentials were decreased in amplitude, with normal ulnar and median motor responses. Needle electromyography of muscles proximally and distally showed diffuse spontaneous firing of muscles ranging in frequency with waxing and waning characteristics. These findings were thought to be consistent with a primary hyperexcitable disorder of muscles with a superimposed old polyradiculoneuropathy and possibly a myopathy. Expanded autoimmune neuroimmunologic testing of serum identified immunoglobulin G-directed cerebellar molecular staining consistent with voltage-gated potassium channel autoantibodies. Radioimmunoprecipitation assay identified voltage-gated potassium channel-immunoglobulin Gs and led to reflex testing for contactin-associated protein 2-immunoglobulin G; autoantibodies were positive. Computed tomography of the chest with contrast was performed, and lymphadenopathy was identified. The patient was clinically diagnosed with contactin-associated protein 2 - immunoglobulin G–positive Isaacs syndrome. A trial of high-dose gabapentin was attempted, with only mild benefits. Next, intravenous immunoglobulin was initiated. Diabetes developed, and he was hospitalized requiring initiation of insulin. His condition is now managed variably with intravenous immunoglobulin and scheduled daily gabapentin. The immune system has long been recognized to help regulate pain via non- immunoglobulin G–mediated mechanisms. Specifically, cytokines decrease the nociceptive nerve fiber thresholds and are released after diverse tissue insults. This allows for speeded healing by increased blood flow and protection of the region by pain guarding mechanisms. It is now recognized that, in rare cases, immunoglobulin G-mediated autoimmunity can lead to otherwise idiopathic pain disorders.

Dendritic origin of late events in optical recordings from salamander olfactory bulb

1992 ◽  
Vol 68 (3) ◽  
pp. 786-806 ◽  
Author(s):  
A. R. Cinelli ◽  
B. M. Salzberg
Keyword(s):  
Olfactory Bulb ◽  
Time Course ◽  
Slow Component ◽  
Field Potential ◽  
Olfactory Nerve ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Direct Stimulation ◽  
Compound Action

1. Optical recordings of membrane-potential changes were used to characterize the origin and properties of the electrical signals from the dendritic level in slices of the salamander olfactory bulb. 2. The optical events were correlated with field-potential waves recorded simultaneously. Both responses exhibited patterns similar to those found in other species. 3. Orthodromic stimulation evoked a compound action potential in the olfactory nerve fibers, followed by two additional principal waves (N1 and N2). These field-potential waves reflected excitatory postsynaptic potentials at the primary mitral/tufted and granule cell dendrites, respectively. 4. Extrinsic optical signals from horizontal slices stained with the pyrazo-oxonal dye RH-155 showed a characteristic sequence of depolarizing and hyperpolarizing events. All of the signals exhibited a wavelength dependence expected for this dye and were abolished in the presence of high K+ in the bath. 5. According to their time courses, depolarizing responses under normal recording conditions were divided into two components, fast and slow. Orthodromic stimuli evoked a fast presynaptic response that represents synchronous compound action potentials from olfactory nerve fibers. At subglomerular levels, additional fast responses could often be recorded at the peri/subglomerular level and in the mitral/tufted somata region. These postsynaptic responses partially coincided with the rising phase of a different depolarizing signal, a slow component characterized by its prolonged time course. 6. With orthodromic stimulation, this slow signal attained its largest amplitude in the zone between the glomeruli and the superficial part of the external plexiform layer (EPL). Antidromic stimuli evoked a signal with some similarities to the one evoked orthodromically, but originating in deeper EPL regions. 7. Slow components were characterized by their Ca dependence. Low Ca2+ medium, or calcium channel blockers, suppressed this optical component, whether evoked orthodromically, antidromically, or by direct stimulation. In addition, Ba2+ (2.5–3.6 mM) in the bath did not abolish these responses, suggesting that they do not reflect a glial depolarization in response to elevated extracellular K+ concentration ([K+]o). 8. Locally applied stimuli next to the glomerular layer elicited these signals in 5–10 microM tetrodotoxin (TTX) or in low extracellular Na+ concentration ([Na+]o) medium, but antidromic or orthodromic stimuli failed to evoke the response under these conditions. The sizes of the responses to local stimuli remained constant, but an increase in their duration was observed in either TTX or low [Na+]o. 9. gamma-Aminobutyric acid (GABA) and baclofen reduced the size of the slow components in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Facial Nerve Compression on the Stapedial Nerve

1984 ◽  
Vol 93 (3_suppl) ◽  
pp. 7-11 ◽  
Author(s):  
Yasushi Matsumoto ◽  
Shingo Murakami ◽  
Naoaki Yanagihara ◽  
Hiroshi Fujita
Keyword(s):  
Facial Nerve ◽  
Functional Recovery ◽  
Histological Finding ◽  
Average Diameter ◽  
Nerve Fibers ◽  
Factors Influencing ◽  
Stapedius Muscle ◽  
Orbicularis Oris Muscle ◽  
Stapedial Reflex ◽  
Series Of Experiments

A series of experiments on guinea pigs was conducted to determine the prognostic dependability of the stapedial reflex measurement in Bell's palsy. Comparison of the threshold of evoked electromyographic response of the stapedius muscle with that of the orbicularis oris muscle revealed that the stapedial nerve had a lower excitability than did the nerve innervating the orbicularis oris muscle. This lower excitability correlates with the histological finding that the stapedial nerve fibers have a smaller average diameter. The results indicate the resistance of the stapedial nerve to injury of the facial nerve. Functional recovery after cramping of the facial nerve tended to occur later in the stapedial nerve than in the nerve innervating the orbicularis oris muscle. The resistance of the stapedial nerve and the longer period required to recover function in this nerve were factors influencing the prognostic ambiguity of this test.

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