Targeting specific brain districts for advanced nanotherapies: A review from the perspective of precision nanomedicine.

Numerous studies are focused on nanoparticle penetration into the brain functionalizing them with ligands useful to cross the blood-brain barrier. However, cell targeting is also crucial, given that cerebral pathologies frequently affect specific brain cells or areas. Functionalize nanoparticles with the most appropriate targeting elements, tailor their physical parameters, and consider the brain's complex anatomy are essential aspects for precise therapy and diagnosis.

Biocompatibility and Endothelial Permeability of Branched Polyglycidols Generated by Ring-Opening Polymerization of Glycidol with B(CF) under Dry and Wet Conditions.

Polyglycidol or polyglycerol (PG), a polyether widely used in biomedical applications, has not been extensively studied in its branched cyclic form (PG), despite extensive research on hyperbranched PG (HPG). This study explores the biomedical promise of PG, particularly its ability to cross the blood-brain barrier (BBB). We evaluate biocompatibility, endothelial permeability, and formation of branched linear PG (PG) as topological impurities in the presence of water.

Neuromuscular Electrical Stimulation Does Not Influence Spinal Excitability in Multiple Sclerosis Patients.

(1) : Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, under three experimental conditions involving the ankle planta flexor muscles: (1) passive NMES (pNMES); (2) NMES superimposed onto isometric voluntary contraction (NMES+); and (3) isometric voluntary contraction (ISO).

Cerebrospinal fluid inflammatory biomarkers predicting interferon-beta response in MS patients.

Background And Aims: Interferon beta (IFNb) is a safe first-line drug commonly used for relapsing-remitting (RR)-MS. Nevertheless, a considerable proportion of patients do not respond to IFNb treatment. Therefore, until now, a number of studies have investigated various markers that could predict the patients who would respond to IFNb therapy.

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis.

Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability and disease activity. Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 103 individuals with other non-inflammatory neurological diseases.

Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients.

Objectives: Skill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS.

Fingolimod Immune Effects Beyond Its Sequestration Ability.

Fingolimod is the first orally administered drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). This drug, modulating sphingosine receptors, regulates the trafficking of lymphocytes between primary and secondary lymphoid organs, trapping naïve T cells and central memory T cells in secondary lymphoid organs, without affecting effector memory T cells and therefore without compromising immunosurveillance. Additionally, fingolimod inhibits expression of Th1 and Th17 cytokines and enhances regulatory T-cell differentiation.

Efficacy of different rituximab therapeutic strategies in patients with neuromyelitis optica spectrum disorders.

Objective: To evaluate disease activity according to rituximab (RTX) induction and maintenance regimens in a multicenter real-life dataset of NMOSD patients.

Methods: This is an observational-retrospective multicentre study including patients with NMOSD treated with RTX in 21 Italian and 1 Swiss centers. Demographics, relapse rate and adverse events over the follow-up were summarized taking into account induction strategy (two-1 g infusions at a 15-day interval (IND-A) vs.

Interleukin-6 Disrupts Synaptic Plasticity and Impairs Tissue Damage Compensation in Multiple Sclerosis.

Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). In the present study, we explored whether interleukin (IL)-6, a major proinflammatory cytokine involved in MS pathogenesis, alters synaptic plasticity and affects the ability to compensate for ongoing brain damage.

Obesity worsens central inflammation and disability in multiple sclerosis.

Background: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS).

Objectives: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity.

Methods: In this cross-sectional study, 140 consecutive relapsing-remitting (RR)-MS patients underwent clinical assessment, BMI evaluation, magnetic resonance imaging scan, and blood and CSF collection before any specific drug treatment.

Fingolimod reduces the clinical expression of active demyelinating lesions in MS.

Background: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a.

Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: reduced synthesis or increased catabolism?

Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of levodopa/dopamine stimulated cAMP and cGMP levels, and/or with changes of their catabolism by phosphodiesterase activity in rats with experimental hemiparkinsonism. Microdialysis and tissue homogenates of the striatal tissues demonstrated that extracellular and intracellular cAMP/cGMP levels were lower in dyskinetic animals during the increasing phase of dyskinesias compared to eukinetic animals, but cAMP/cGMP levels increased in dyskinetic animals during the phase of decreasing and extinction of dyskinesias.

Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease.

Importance: Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness.

Objectives: To study cerebrospinal fluid levels of orexin in patients with AD, to evaluate the relationship of orexin cerebrospinal fluid levels with the degree of dementia and the cerebrospinal fluid AD biomarkers (tau proteins and β-amyloid 1-42), and to analyze potentially related sleep architecture changes measured by polysomnography.

Electroencephalography and dementia: a literature review and future perspectives.

While many studies have investigated electroencephalographic (EEG) features of dementia, few have analysed the relationship between EEG and cerebrospinal fluid biomarkers in cognitive impairment. Seizures are frequently observed at the end stage of Alzheimer disease, and experimental animal studies support the view that epileptiform activity may contribute to the cognitive decline. In this paper, after reviewing literature findings concerning the role of EEG in dementia, we show the preliminary results of our study aimed to correlate the presence of epileptiform EEG patterns with cerebrospinal fluid biomarkers in order to better define the prognosis of dementia.

Sundowning syndrome: a possible marker of frailty in Alzheimer's disease?

The term "sundowning" describes a clinical phenomenon characterized by late afternoon exacerbation of behavioural symptoms in dementia. Beyond this clinical definition, the debate around this concept is not properly solved, because many authors define it in different ways, mentioning various hypothetical etiological explanations. It represents a concrete problem, which is difficult to manage for physicians and caregivers, and is probably linked to various biological, psychological and social aspects.