Palmitoylethanolamide (PEA) is an endogenous lipid produced on demand by neurons and glial cells that displays neuroprotective properties. It is well known that inflammation and neuronal damage are strictly related processes and that microglia play a pivotal role in their regulation. The aim of the present work was to assess whether PEA could exert its neuroprotective and anti-inflammatory effects through the modulation of microglia reactive phenotypes. In N9 microglial cells, the pre-incubation with PEA blunted the increase of M1 pro-inflammatory markers induced by lipopolysaccharide (LPS), concomitantly increasing those M2 anti-inflammatory markers. Images of microglial cells were processed to obtain a set of morphological parameters that highlighted the ability of PEA to inhibit the LPS-induced M1 polarization and suggested that PEA might induce the anti-inflammatory M2a phenotype. Functionally, PEA prevented Ca²⁺ transients in both N9 cells and primary microglia and antagonized the neuronal hyperexcitability induced by LPS, as revealed by multi-electrode array (MEA) measurements on primary cortical cultures of neurons, microglia, and astrocyte. Finally, the investigation of the molecular pathway indicated that PEA effects are not mediated by toll-like receptor 4 (TLR4); on the contrary, a partial involvement of cannabinoid type 2 receptor (CB2R) was shown by using a selective receptor inverse agonist.

The transient receptor potential akyrin type-1 (TRPA1) is a non-selective cation channel playing a pivotal role in pain sensation and neurogenic inflammation. TRPA1 channels expressed in the central nervous system (CNS) have a critical role in the modulation of cortical spreading depression (CSD), which is a key pathophysiological basis of migraine pain. ADM_09 is a recently developed lipoic acid-based TRPA1 antagonist that is able to revert oxaliplatin-induced neuropathic pain and inflammatory trigeminal allodynia. In this context, aiming at developing drugs that are able to target TRPA1 channels in the CNS and promote an antioxidant effect, permeability across the blood–brain barrier (BBB) represents a central issue. Niosomes are nanovesicles that can be functionalized with specific ligands selectively recognized by transporters expressed on the BBB. In this work, the activity of ADM_09 on neocortex cultures was studied, and an efficient formulation to cross the BBB was developed with the aim of increasing the concentration of ADM_09 into the brain and selectively delivering it to the CNS rapidly after parenteral administration.

A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. The greater part of these methods does not consider the network as a whole but performs an analysis channel by channel. In this paper we illustrate how a very simple approach that considers the total network activity, is able to show interesting neuronal network features. In particular we perform two different analyses: a connectivity examination studying networks at different days in vitro and an analysis of the long period effects of the administration of two common neuro-active drugs, i.e. TTX and AP5. Our analysis is performed considering burst topology, i.e. cataloguing network bursts as Global (if they involve more than the 25% of the MEA channels) or Local (if less that 25%). This division allows, in the first analysis, to understand the network connectivity (increasing from div 1 to 6) and decreasing till reaching a plateau (from div 6 to 10). The second analysis highlights a substantial difference between the long period effects of TTX and AP5. While TTX induces a massive Global activity explosion, sign of a prolonged inhibitory synapse depression, AP5 shows only a modest Local activity increase, mark of the low effect of NMDA receptors on a mature neuronal network without inputs.

In neurobiology an even bigger role is covered by acquisition and processing of data obtained from micro-electrode array (MEA) technology, where a fixed number of channels record in vitro neural spiking activity. In this work we developed a software-tool implementing a specific method to analyze time data series of this spiking activity. Our aim is to quantify a global measure of correlation and dependence between activities of neurons belonging to different MEA channels. Methods include cross-correlation, mutual information and dynamic time warping. These techniques can extract specific information about behavior of the neurons matrices. In order to synthesize a global measure of correlation in spiking neuron activity, we applied a sub-optimal criterion based on genetic algorithms (GA): GA help us to sort MEA channels with most similar and coordinated activity, and finally to estimate our index of global similarity. Thanks to this index we tried to test the existence of a sort of self-coordinating neuronal network, evolving in time and regulating the ensemble neural behavior under specific external stimuli, such as the chemical ones here studied

In the recent years neuroscience research is exploiting technologies initially developed only for electronic engineering use: this is the case of micro-electrode array (MEA) technology, where a finite number of channels acquires in vitro neural spiking activity. In this work we present a new method to process time data series from MEA trough an ad-hoc software-framework. Our aim is to build a classifier giving quantitative measures of similarity and statistical dependence among neurons activities recorded in different MEA channels. Methods applied to extract specific information about neuronal behavior are mutual information and dynamic time warping. In order to extend the pair-wise information so obtained to the entire neuronal networks on MEA, we have chosen to implement a sub-optimal criterion thanks to genetic algorithms (GA): this technique support us to sort MEA channels based on dependent activity, thus providing a global index. We applied it to test the presence of self-synchronization among neurons, which can evolve in time and adapt their self in response to specific external stimuli, such as those of the chemical neuron-inhibitors here analyzed.