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Journal of Neurology Feb 2019Antibody-mediated encephalitis defines a class of diseases wherein antibodies directed at cell-surface receptors are associated with behavioral and cognitive...
Antibody-mediated encephalitis defines a class of diseases wherein antibodies directed at cell-surface receptors are associated with behavioral and cognitive disturbances. One such recently described encephalitis is due to antibodies directed at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). This entity is exceptionally rare and its clinical phenotype incompletely described. We present findings from two cases of AMPAR encephalitis that exemplify variability in the disease spectrum, and summarize findings in published cases derived from a systematic literature review. When all patients are considered together, the presence of psychiatric symptoms at presentation portended a poor outcome and was associated with the presence of a tumor. Furthermore, we provide evidence to suggest that the topography of magnetic resonance imaging abnormalities in reported cases mirrors the distribution of AMPARs in the human brain. The potential for neurological improvement following immunomodulatory therapy together with the favorable outcome reported in most cases emphasizes the importance of testing for autoantibodies against neuronal cell-surface proteins, including AMPAR, in patients with clinical and neuroimaging findings suggestive of autoimmune encephalitis. Close attention to the clinical phenotype may inform the presence of malignancy and long-term prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases of the Nervous System; Encephalitis; Humans; Male; Middle Aged; Neuroimaging; Receptors, Glutamate; Young Adult
PubMed: 30560455
DOI: 10.1007/s00415-018-9153-8 -
American Journal of Health Behavior Mar 2020There is suggestive evidence that exercise may have a greater effect on visuo-spatial memory, compared to other memory types. However, we have a limited understanding...
There is suggestive evidence that exercise may have a greater effect on visuo-spatial memory, compared to other memory types. However, we have a limited understanding as to the mechanisms through which exercise may subserve visuo-spatial memory. Thus, the purpose of this review is to evaluate the extent to which exercise may influence visuo-spatial memory, whether exercise can attenuate drug- and diseased-induced declines in memory, and determine the underlying mechanisms of these relationships. We employed a systematic review approach. We identified studies using electronic databases, including PubMed, PsychInfo, Sports Discus and Google Scholar. In total, we identified 32 articles. Among these, 2 were among humans and 30 were conducted in animal models. There was strong evidence sup- porting the facilitative role of chronic exercise in visuo-spatial memory improvements, as well as attenuation of drug- and diseased-induced memory decline. There are various mechanisms through which chronic exercise may influence visuo-spatial memory, including increased neuro-genesis, angiogenesis, improved neural efficiency, CB receptor signaling, activation of H₂ receptors, and increased number of synaptic structures (eg, AMPA and NMDA receptors). Exercise may help to enhance visuo-spatial memory.
Topics: Animals; Exercise; Exercise Therapy; Humans; Memory Disorders; Physical Conditioning, Animal; Spatial Memory
PubMed: 32019650
DOI: 10.5993/AJHB.44.2.5 -
Journal of Cerebral Blood Flow and... Jul 2018Spreading depolarization (SD) occurs alongside brain injuries and it can lead to neuronal damage. Therefore, pharmacological modulation of SD can constitute a...
Spreading depolarization (SD) occurs alongside brain injuries and it can lead to neuronal damage. Therefore, pharmacological modulation of SD can constitute a therapeutic approach to reduce its detrimental effects and to improve the clinical outcome of patients. The major objective of this article was to produce a systematic review of all the drugs that have been tested against SD. Of the substances that have been examined, most have been shown to modulate certain SD characteristics. Only a few have succeeded in significantly inhibiting SD. We present a variety of strategies that have been proposed to overcome the notorious harmfulness and pharmacoresistance of SD. Information on clinically used anesthetic, sedative, hypnotic agents, anti-migraine drugs, anticonvulsants and various other substances have been compiled and reviewed with respect to the efficacy against SD, in order to answer the question of whether a drug at safe doses could be of therapeutic use against SD in humans.
Topics: Brain Injuries; Humans; Neuromuscular Depolarizing Agents; Neurons
PubMed: 29673289
DOI: 10.1177/0271678X18771440 -
Epilepsy & Behavior : E&B Sep 2018Perampanel (PER) is a noncompetitive β-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor antagonist with demonstrated efficacy in animal models of...
OBJECTIVE
Perampanel (PER) is a noncompetitive β-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor antagonist with demonstrated efficacy in animal models of status epilepticus (SE). We performed a systematic review of the literature to assess the efficacy and tolerability of PER in the treatment of refractory and super-refractory SE.
METHODS
We searched Medline, Embase, and CENTRAL (accessed from inception to April 30, 2018) to identify studies evaluating oral PER as treatment of SE of any type. We also searched the OpenGrey repository and conference proceedings of international congresses by the International League Against Epilepsy and by the American Epilepsy Society from 2012 onwards.
RESULTS
Ten articles were included, with a total of 69 episodes of SE occurring in 68 patients (aged 18 to 91 years). The type and etiology of SE varied remarkably across studies. The number of drugs used prior to PER ranged from 1 to 9. The time from SE onset to PER administration ranged from 9.25 h to 35 days. The initial PER dose ranged from 2 to 32 mg. The proportion of patients achieving clinical SE cessation varied from 17% to 100%. The time from PER administration to SE cessation ranged from 1 h to 4 weeks.
CONCLUSIONS
The currently available evidence supporting the use of PER in SE is weak and hampered by several confounding factors. Further studies should be performed in more clinically homogeneous and larger cohorts to evaluate the efficacy and safety of PER administered in earlier stages of SE, at higher dosages, and at intervals shorter than 24 h.
Topics: Animals; Anticonvulsants; Humans; Nitriles; Pyridones; Receptors, AMPA; Status Epilepticus; Treatment Outcome
PubMed: 30076046
DOI: 10.1016/j.yebeh.2018.07.004 -
Frontiers in Neurology 2019Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of...
Autoimmune encephalitides (AIE) comprise a group of inflammatory diseases of the central nervous system (CNS), which can be further characterized by the presence of different antineuronal antibodies. Recently, a clinical approach for diagnostic criteria for the suspected diagnosis of AIE as well as definitive AIE were proposed. These are intended to guide physicians when to order the antineuronal antibody testing and/or facilitate early diagnosis even prior to the availability of the specific disease-confirming test results to facilitate prompt treatment. These diagnostic criteria also include the results of basic cerebrospinal fluid (CSF) analysis. However, the different antibody-defined AIE subtypes might be highly distinct with regard to their immune pathophysiology, e.g., the pre-dominance of specific IgG subclasses, IgG1, or IgG4, or frequency of paraneoplastic compared to idiopathic origin. Thus, it is conceivable that the results of basic CSF analysis might also be very different. However, this has not been explored systematically. Here, we systematically reviewed the literature about the 10 most important AIE subtypes, AIE with antibodies against NMDA, AMPA, glycine, GABA, and GABA receptors as well as DPPX, CASPR2, LGI1, IgLON5, or glutamate decarboxylase (GAD), with respect to the reported basic CSF findings comprising CSF leukocyte count, total protein, and the presence of oligoclonal bands (OCB) restricted to the CSF as a sensitive measure for intrathecal IgG synthesis. Our results indicate that these basic CSF findings are profoundly different among the 10 different AIE subtypes. Whereas, AIEs with antibodies against NMDA, GABA, and AMPA receptors as well as DPPX show rather frequent inflammatory CSF changes, in AIEs with either CASPR2, LGI1, GABA, or glycine receptor antibodies CSF findings were mostly normal. Two subtypes, AIEs defined by either GAD, or IgLON5 antibodies, did not fit into this general pattern. In AIE with GAD antibodies, positive OCBs in the absence of other changes were typical, while the CSF in IgLON5 antibody-positive AIE was characterized by elevated protein.
PubMed: 31404257
DOI: 10.3389/fneur.2019.00804 -
PloS One 2019Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent...
Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent restabilisation. Different molecular mechanisms have been postulated for destabilisation in the amygdala and hippocampus, including CB1 receptor activation, protein degradation and AMPA receptor exchange; however, most of the amygdala studies have used pre-reexposure interventions, while those in the hippocampus have usually performed them after reexposure. To test whether the temporal window for destabilisation is similar across both structures, we trained Lister Hooded rats in a contextual fear conditioning task, and 1 day later performed memory reexposure followed by injection of either the NMDA antagonist MK-801 (0.1 mg/kg) or saline in order to block reconsolidation. In parallel, we also performed local injections of either the CB1 antagonist SR141716A or its vehicle in the hippocampus or in the amygdala, either immediately before or immediately after reactivation. Infusion of SR141716A in the hippocampus prevented the reconsolidation-blocking effect of MK-801 when performed after reexposure, but not before it. In the amygdala, meanwhile, pre-reexposure infusions of SR141716A impaired reconsolidation blockade by MK-801, although the time-dependency of this effect was not as clear as in the hippocampus. Our results suggest the temporal windows for CB1-receptor-mediated memory destabilisation during reconsolidation vary between brain structures. Whether this reflects different time windows for engagement of these structures or different roles played by CB1 receptors in destabilisation across structures remains an open question for future studies.
Topics: Amygdala; Animals; Behavior, Animal; Cannabinoid Receptor Antagonists; Conditioning, Classical; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Fear; Hippocampus; Male; Memory; Models, Animal; Rats; Receptor, Cannabinoid, CB1; Receptors, AMPA; Rimonabant; Time Factors
PubMed: 30645588
DOI: 10.1371/journal.pone.0205781 -
Frontiers in Psychiatry 2022The mechanism of action underlying ketamine's rapid antidepressant effects in patients with depression, both suffering from major depressive disorder (MDD) and bipolar...
The mechanism of action underlying ketamine's rapid antidepressant effects in patients with depression, both suffering from major depressive disorder (MDD) and bipolar disorder (BD), including treatment resistant depression (TRD), remains unclear. Of the many speculated routes that ketamine may act through, restoring deficits in neuroplasticity may be the most parsimonious mechanism in both human patients and preclinical models of depression. Here, we conducted a literature search using PubMed for any reports of ketamine inducing neuroplasticity relevant to depression, to identify cellular and molecular events, relevant to neuroplasticity, immediately observed with rapid mood improvements in humans or antidepressant-like effects in animals. After screening reports using our inclusion/exclusion criteria, 139 publications with data from cell cultures, animal models, and patients with BD or MDD were included (registered on PROSPERO, ID: CRD42019123346). We found accumulating evidence to support that ketamine induces an increase in molecules involved in modulating neuroplasticity, and that these changes are paired with rapid antidepressant effects. Molecules or complexes of high interest include glutamate, AMPA receptors (AMPAR), mTOR, BDNF/TrkB, VGF, eEF2K, p70S6K, GSK-3, IGF2, Erk, and microRNAs. In summary, these studies suggest a robust relationship between improvements in mood, and ketamine-induced increases in molecular neuroplasticity, particularly regarding intracellular signaling molecules.
PubMed: 35546951
DOI: 10.3389/fpsyt.2022.860882