Publications by authors named "Giacinto Bagetta"

Background: According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances.

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Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and is prescribed off-label for several neurological conditions like neuropathic pain, migraines and anxiety. Besides their action on the reuptake of monoaminergic neurotransmitters, tricyclic antidepressants interact with several additional targets that may contribute to either therapeutic or adverse effects. Here, we investigated the effects of amitriptyline on proliferation and autophagy (i.

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Ischemic preconditioning (PC) induced by a sub-lethal cerebral insult triggers brain tolerance against a subsequent severe injury through diverse mechanisms, including the modulation of the immune system. Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, has recently been involved in the regulation of the neuroimmune response following ischemic stroke. Thus, we aimed at assessing whether the neuroprotective effects of ischemic PC involve the modulation of TSG-6 in a murine model of transient middle cerebral artery occlusion (MCAo).

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Article Synopsis
  • Approximately 57.4 million people worldwide are affected by dementia, with behavioral and psychological symptoms (BPSD), particularly agitation, being prevalent and often challenging to manage.
  • The BRAINAID trial tested a nanotechnology device, NanoBEO, on 29 elderly patients (65+) with severe dementia to evaluate its effectiveness in reducing agitation and pain, utilizing a randomized and placebo-controlled design.
  • Results indicated that NanoBEO significantly reduced agitation levels and frequency by 28% after 4 weeks, and showed notable pain relief (45.46% improvement) after just 1 week, without requiring additional medications.
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The global impact of dementia is an increasing area of concern and, according to the Alzheimer's Disease International (ADI) World Alzheimer Report 2021, up to 90% of dementia patients in low- and middle-income countries are not diagnosed [...

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A complication of diabetes is neuropathic pain, which is difficult to control with medication. We have confirmed that neuropathic pain due to mechanical allodynia in diabetic mice is mediated by a characteristic neuropeptide in the spinal cord. We evaluated the strength of mechanical allodynia in mice using von Frey filaments.

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Hericenone C is one of the most abundant secondary metabolites derived from Hericium erinaceus, under investigation for medicinal properties. Here, we report that Hericenone C inhibits the second phase of formalin-induced nociceptive behavior in mice. As the second phase is involved in inflammation, in a mechanistic analysis on cultured cells targeting NF-κB response element (NRE): luciferase (Luc)-expressing cells, lipopolysaccharide (LPS)-induced NRE::Luc luciferase activity was found to be significantly inhibited by Hericenone C.

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Bergamot essential oil shows anxiolytic-relaxant effects devoid of sedative action and motor impairment typical of benzodiazepines. Considering the potential for clinical of these effects, it is important to understand the underlying mechanisms of the phytocomplex. Modulation of glutamate group I and II metabotropic receptors is involved in stress and anxiety disorders, in cognition and emotions and increases locomotor activity and wakefulness.

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The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches.

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Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative diseases and accounts for the majority of dementia cases worldwide. Tremendous ongoing efforts of basic and clinical research have expanded our knowledge on AD and its complex multifactorial pathogenesis. For sporadic AD, it is widely assumed that silent and early symptomatic stages initiate decades before the irreversible decline in cognitive abilities that ultimately lead to debilitating conditions.

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The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%.

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Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working memory, discriminative memory, anxiety, and motor activity in the presence of intranasal PEA-OXA, a dual antagonist of presynaptic α2 and H3 receptors.

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Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice.

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Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010.

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Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the role of natural products. The present systematic review and meta-analysis aims at appraising for the first time the efficacy of aromatherapy in cancer pain in clinical studies with different design according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations.

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The identification of novel targets to modulate the immune response triggered by cerebral ischemia is crucial to promote the development of effective stroke therapeutics. Since tumour necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, is involved in the regulation of immune and stromal cell functions in acute neurodegeneration, we aimed to characterize its involvement in ischemic stroke. Transient middle cerebral artery occlusion (1 h MCAo, followed by 6 to 48 of reperfusion) in mice resulted in a significant elevation in cerebral TSG-6 protein levels, mainly localized in neurons and myeloid cells of the lesioned hemisphere.

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Multicentre preclinical randomized controlled trials (pRCTs) are a valuable tool to improve experimental stroke research, but are challenging and therefore underused. A common challenge regards the standardization of procedures across centres. We here present the harmonization phase for the quantification of sensorimotor deficits by composite neuroscore, which was the primary outcome of two multicentre pRCTs assessing remote ischemic conditioning in rodent models of ischemic stroke.

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Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), the first soluble chemokine-binding protein to be identified in mammals, inhibits chemotaxis and transendothelial migration of neutrophils and attenuates the inflammatory response of dendritic cells, macrophages, monocytes, and T cells. This immunoregulatory protein is a pivotal mediator of the therapeutic efficacy of mesenchymal stem/stromal cells (MSC) in diverse pathological conditions, including neuroinflammation. However, TSG-6 is also constitutively expressed in some tissues, such as the brain and spinal cord, and is generally upregulated in response to inflammation in monocytes/macrophages, dendritic cells, astrocytes, vascular smooth muscle cells and fibroblasts.

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Article Synopsis
  • - Migraine is a major cause of disability for people under 50, worsened by the effects of a protein called CGRP, leading to chronic migraine issues.
  • - New treatments called gepants, which block the CGRP receptor, have evolved from older, possibly harmful drugs to safer options like oral rimegepant and ubrogepant, and the recently approved intranasal zavegepant.
  • - The study aims to review the development of zavegepant and explore its potential in treating migraines, while also noting the need for more real-world data on the safety and effectiveness of these newer treatments.
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Some 30−50% of the global population and almost 20% of the European population actually suffer from chronic pain, which presents a tremendous burden to society when this pain turns into a disability and hospitalization. Palmitoylethanolamide (PEA) has been demonstrated to improve pain in preclinical contexts, but an appraisal of clinical evidence is still lacking. The present study aimed at addressing the working hypothesis for the efficacy of PEA for nociceptive musculoskeletal and neuropathic pain in the clinical setting.

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OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment.

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Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics.

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Murine models are fundamental in the study of clinical conditions and the development of new drugs and treatments. Transgenic technology has started to offer advantages in oncology, encompassing all research fields related to the study of painful syndromes. Knockout mice or mice overexpressing genes encoding for proteins linked to pain development and maintenance can be produced and pain models can be applied to transgenic mice to model the most disabling neurological conditions.

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