Extensive researches have deepened knowledge on the role of synaptic components in epileptogenesis, but limited attention has been devoted to the potential implication of the cytoskeleton. The study ...of the development of epilepsy and hyperexcitability states involves molecular, synaptic, and structural alterations of neuronal bioelectric activity. In this paper we aim to explore the neurobiological targets involved in microtubule functioning and cytoskeletal transport, i.e. how dynamic scaffolding of microtubules can influence neuronal morphology and excitability, in order to suggest a potential role for microtubule dynamics in the processes turning a normal neuronal network in a hyperexcited one. Pathophysiological alterations of microtubule dynamics inducing neurodegeneration, network remodeling and relative impairment on synaptic transmission were overviewed. Recent researches were reported on the phosphorylation state of microtubule-associated proteins such as tau in neurodegenerative diseases and epileptic states, but also on the effect of microtubule-active agents influencing cytoskeleton destabilization in epilepsy models. The manipulation of microtubule polymerization was found effective in the modulation of hyperexcitability. In addition, it was considered the importance of microtubules and related neurotrophic factors during neural development since they are essential for the formation of a properly functional neuronal network. Otherwise, this can lead to cognitive deficits, hyperexcitability phenomena and neurodevelopmental disorders. Lastly, we evaluated the role of microtubule dynamics on neuronal efficiency considering their importance in the transport of mitochondria, cellular elements fulfilling energy requirements for neuronal activity, and a putative influence on cannabinoid-mediated neuroprotection. This review provides novel perspectives for the implication of microtubule dynamics in the development of epileptic phenomena.
Endocannabinoid system is considered a relevant player in the regulation of neuronal excitability, since it contributes to maintaining the balance of the synaptic ionic milieu. Perturbations to ...bioelectric conductances have been implicated in the pathophysiological processes leading to hyperexcitability and epileptic seizures. Cannabinoid influence on neurosignalling is exerted on classic receptor-mediated mechanisms or on further molecular targets. Among these, transient receptor potential vanilloid (TRPV) are ionic channels modulated by cannabinoids that are involved in the transduction of a plethora of stimuli and trigger fundamental downstream pathways in the post-synaptic site. In this review, we aim at providing a brief summary of the most recent data about the cross-talk between cannabinoid system and TRPV channels, drawing attention on their role on neuronal hyperexcitability. Then, we aim to unveil a plausible point of interaction between these neural signalling systems taking into consideration nitric oxide, a gaseous molecule inducing profound modifications to neural performances. From this novel perspective, we struggle to propose innovative cellular mechanisms in the regulation of hyperexcitability phenomena, with the goal of exploring plausible CB-related mechanisms underpinning epileptic seizures.
Ketogenic Diet is a nutritional pattern often used as dietotherapy in inflammatory diseases, including neurological disorders. Applied on epileptic children since 1920, in recent years it has been ...taken into account again as a tool to both reduce inflammatory burdens and ameliorate the nutritional status of patients affected by different pathologies. Multiple sclerosis (MS) is considered an immune-mediated neuro-inflammatory disease and diet is a possible factor in its pathogenesis. The aim of this work is to investigate the main potential targets of MS-related impairments, in particular the cognitive deficits, focusing on the alteration of biomarkers such as the Brain Derived-Neurotrophic Factor and the Tryptophan/Kynurenine ratio that could play a role on neuroprotection and thus on MS progression. Furthermore, we here propose nutritional suggestions which are useful in the development of a ketogenic diet protocol that takes advantage of the anti-inflammatory properties of low-carbohydrate foods from the Mediterranean diet to be applied to subjects with MS. In conclusion, this approach will allow one to develop the ketogenic diet combined with a modified Mediterranean diet as a possible tool to improve neuroinflammation in multiple sclerosis.
Evidence by functional imaging studies suggests the role of left DLPFC in the inhibitory control of nociceptive transmission system. Pain exerts an inhibitory modulation on motor cortex, reducing MEP ...amplitude, while the effect of pain on motor intracortical excitability has not been studied so far. In the present study, we explored in healthy subjects the effect of capsaicin-induced pain and the modulatory influences of left DLPFC stimulation on motor corticospinal and intracortical excitability. Capsaicin was applied on the dorsal surface of the right hand, and measures of motor corticospinal excitability (test-MEP) and short intracortical inhibition (SICI) and facilitation (ICF) were obtained by paired-pulse TMS on left motor cortex. Evaluations were made before and at different times after capsaicin application in two separate sessions: without and with high-frequency rTMS of left DLPF cortex, delivered 10 min. after capsaicin application. We performed also two control experiments to explore: 1: the effects of Left DLPFC rTMS on capsaicin-induced pain; 2: the modulatory influence of left DLPFC rTMS on motor cortex without capsaicin application. Capsaicin-induced pain significantly reduced test MEP amplitude and decreased SICI leaving ICF unchanged. Left DLPFC rTMS, together with the analgesic effect, was able to revert the effects of capsaicin-induced pain on motor cortex restoring normal MEP and SICI levels. These data support the notion that that tonic pain exerts modulatory influence on motor intracortical excitability; the activation of left DLPFC by hf rTMS could have analgesic effects, reverting also the motor cortex excitability changes induced by pain stimulation.
In the original publication of the article, the names of the authors were incorrectly swapped as Gambino Giuditta · Rizzo Valerio · Giglia Giuseppe · Ferraro Giuseppe · Sardo Pierangelo.
Migraine is a highly disabling disease characterized by recurrent pain. Despite an intensive effort, mechanisms of migraine pathophysiology still represent an unsolved issue. Evidence from both ...animal and human studies suggests that migraine is characterized by hyperresponsivity or hyperexcitability of sensory cortices, especially the visual cortex. This phenomenon, in turn, may affect multisensory processing. Indeed, migraineurs present with an abnormal, reduced, perception of the Sound-induced Flash Illusion (SiFI), a crossmodal illusion that relies on optimal integration of visual and auditory stimuli by the occipital visual cortex. Decreasing visual cortical excitability with transcranial direct current stimulation (tDCS) can increase the SiFI in healthy subjects. Moving away from these issues, we applied cathodal tDCS over the visual cortex of migraineurs, with and without aura, in order to decrease cortical excitability and thus physiologically restoring the perception of a reliable SiFI. Differently from our expectations, tDCS was unable to reliably modulate SiFI in migraine. The chronic, relatively excessive, visual cortex hyperexcitability, featuring the migraineur brain, may render tDCS ineffective for restoring multisensory processing in this disease.
A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. ...Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus.
Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels.
Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling.
This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies.
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Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ...ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.
Perception is a complex, neural mechanism that requires organization and interpretation of input meaning and it has been a key topic in medicine, neuroscience and philosophy for centuries. Gestalt ...psychology proposed that the underlying mechanism is a constructive process that depends on both input of stimuli and the sensory-motor state of the agent. The Bayesian Brain hypothesis reframed it as probabilistic inference of previous beliefs, which are revised to accommodate new information. The Predictive Coding Theory proposes that this process is implemented through a top-down cascade of cortical predictions of lower level input and the concurrent propagation of a bottom-up prediction error aimed at revising higher level expectations. The ‘Active Inference’ theory explains both perception and action, generalising the prediction error minimisation process. In this focused-review we provide a historical overview of the topic and an intuitive approach to the new computational models.
This study aimed to describe the specific localization and anatomical pattern of 24 feline lymphomas of the nervous system for which the immunophenotype was identified by immunohistochemistry ...investigations to support the potential specific correlation between subtypes and anatomical patterns. In total 10 tumors affected the spinal cord, eight the brain, four the peripheral nerves, one involved both the brain and the spinal cord, and one simultaneously the brain and the optic nerves. Twenty two tumors were primary lymphomas. The affected animals were 8 years of mean age. Tumors developed as an extra-axial mass (11 cases), intra-axial mass (six cases), leptomeningeal lymphomatosis (three cases), and neurolymphomatosis (five cases). One of them expressed both leptomeningeal lymphomatosis and neurolymphomatosis patterns. Two intra-axial brain lymphomas showed an angiotropic pattern. The optic chiasm was the most involved site for neurolymphomatosis. Immunolabeling was performed using anti-CD3, CD20, CD79a, PAX5, MUM-1, CD56, and anti-CD44 antibodies. In total, 12 tumors consisted of B cell lymphomas, and six of T cell lymphomas, two cases were double-reactive lymphomas while two cases consisted of non-B non-T lymphomas. B cell lymphoma affected animals of 6.4 years of mean age, while the T cell lymphoma affected older animals (mean age of 11.1 years). Extra-axial tumors mainly consisted of B cell lymphomas (8/11). Neurolymphomatosis expressed different immunophenotypes, and the B cell phenotype was the most prevalent in the optic chiasm. Two leptomeningeal lymphomatoses expressed T cell immunophenotype. For the first time, plasmacytoid differentiation was found for angiotropic lymphoma and neurolymphomatosis. All the cases, except one, were CD56-negative. CD44-expression confirmed a common malignant potential for all the anatomical patterns of the nervous system lymphoma in cats. Immunophenotype of feline lymphoma of the nervous system and its potential association with specific anatomical patterns should be strongly required in the diagnostic workup and clinical approach to this tumor especially when its primary origin is confirmed.
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