Microvesicles (MVs) are released by most cell types in physiological conditions, but their number is often increased upon cellular activation or neoplastic transformation. This suggests that their detection may be helpful in pathological conditions to have information on activated cell types and, possibly, on the nature of the activation. This could be of paramount importance in districts and tissues that are not accessible to direct examination, such as the central nervous system. Increased release of MVs has been described to be associated to the acute or active phase of several neurological disorders. While the subcellular origin of MVs (exosome or ectosomes) is basically never addressed in these studies because of technical limitations, the cell of origin is always identified. Endothelium- or platelet-derived MVs, detected in plasma or serum, are linked to neurological pathologies with a vascular or ischemic pathogenic component, and may represent a very useful marker to support therapeutic choices in stroke. In neuroinflammatory disorders, such as multiple sclerosis, MVs of oligodendroglial, or microglial origin have been described in the cerebrospinal fluid and may carry, in perspective, additional information on the biological alterations in their cell of origin. Little specific evidence is available in neurodegenerative disorders and, specifically, MVs of neural origin have never been investigated in these pathologies. Few data have been reported for neuroinfection and brain trauma. In brain tumors, despite the limited number of studies performed, results are very promising and potentially close to clinical translation. We here review all currently available data on the detection of MVs in neurological diseases, limiting our search to exclusively human studies. Current literature and our own data indicate that MVs detection may represent a very promising strategy to gain pathogenic information, identify therapeutic targets, and select specific biomarkers for neurological disorders.

Background. Oxidative stress is well documented in multiple sclerosis (MS) lesions, but its correspondence at peripheral level is still controversial. Objective. To evaluate peripheral oxidative stress markers in MS patients. Methods. We studied total blood levels of Coenzyme Q10 (CoQ10), oxidized and reduced forms of glutathione, malondialdehyde, reactive oxygen species (ROS), anti-oxidized-low-density lipoproteins (anti-oxLDL) antibodies, and antioxidant power (PAO) in 87 patients with different MS clinical phenotypes and in 77 controls. Results. CoQ10 was lower whereas anti-oxLDL antibodies titer was higher in MS patients than in controls. The benign variant of MS displayed both higher CoQ10 and higher anti-oxLDL than other MS clinical variants. Female patients had lower CoQ10 and PAO and higher ROS than male patients. Differences were greater in younger patients with shorter disease duration. Surprisingly, there was no difference for these markers between treated and untreated patients. Conclusion. We found lower antioxidant agents and higher anti-oxLDL antibodies in MS, and the highest antibody titers occurred in the benign form. We suggest that natural anti-oxLDL antibodies can be protective against MS, saving blood brain barrier integrity. Our findings also suggest that milder MS is associated with a distinct oxidative stress pattern, which may provide a useful biomarker of disease prognosis.

Erdheim–Chester disease (ECD) is a rare form of systemic histiocytosis characterized by the diffuse infiltration of tissues by lipid-laden macrophages. As the clinical course and prognosis are highly influenced by site of disease involvement, ECD course ranges from asymptomatic to life threatening, with a reported global 5-year mortality of 30–40%. Whether ECD is an inflammatory or clonal disease in its nature has long been debated. The disease is characterized by a network of pro-inflammatory cyto/chemokines responsible for the recruitment and activation of histiocytes into ECD lesions, similarly to what reported in Langerhans cell histiocytosis (LCH). Growing evidence supports a central role of the oncogenic BRAFV600E mutation in histiocytosis pathogenesis, and suggests oncogene-induced senescence (OIS), a major protective mechanism against oncogenic events characterized by cell-cycle arrest and the induction of pro-inflammatory molecules, as the possible link between the oncogenic mutation and the observed inflammation. Indeed, ECD recapitulates in vivo the molecular events associated with OIS, i.e., cell-cycle arrest and a potent local inflammatory response. Accordingly, the infiltration of different tissues by macrophages and the inflammatory local and systemic effects observed in ECD likely represent a drawback of OIS. Therefore, these findings delineate a new conception of OIS as a new pathogenic mechanism intrinsically responsible for disease development.

Alzheimer's disease (AD) is the most common form of dementia, while mild cognitive impairment (MCI) causes a slight but measurable decline in cognitive abilities. A person with MCI has an increased risk of developing AD or another dementia. Thus, it is of medical interest to develop predictive tools to assess this risk. A growing awareness exists that pro-oxidative state and neuro-inflammation are both involved in AD. However, the extent of this relationship is still a matter of debate. Due to the expected non-linear correlations between oxidative and inflammatory markers, traditional statistics is unsuitable to dissect their relationship with the disease. Artificial neural networks (ANNs) are computational models inspired by central nervous system networks, capable of machine learning and pattern recognition. The aim of this work was to disclose the relationship between immunological and oxidative stress markers in AD and MCI by the application of ANNs. Through a machine learning approach, we were able to construct an algorithm to classify MCI and AD with high accuracy. Such an instrument, requiring a small amount of immunological and oxidative-stress parameters, would be useful in the clinical practice. Moreover, applying an innovative non-linear mathematical technique, a global immune deficit was shown to be associated with cognitive impairment. Surprisingly, both adaptive and innate immunity were peripherally defective in AD and MCI patients. From this study, new pathogenetic aspects of these diseases could emerge.