The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b+ cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an “oxidative stress memory” both in the periphery and CNS compartments, in chronic neuroinflammation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1497-x) contains supplementary material, which is available to authorized users.

<b><i>Background:</i></b> Berlin is internationally known for its nightlife. In a nation-wide and Europe-wide comparison, the use of legal and illegal substances is comparatively higher in Berlin than in other similar cities. However, few data exist about the drug use in the party scene. <b><i>Objective:</i></b> This study aims to assess the sociodemographic characteristics of Berlin’s party scene and its patterns of substance use as well as expectations towards prevention in order to derive appropriate preventive measures. <b><i>Methods:</i></b> Using questionnaires, both online (<i>n</i> = 674) and in the field (<i>n</i> = 203), a total of 877 people of the Berlin party scene were interviewed. The questionnaires ascertained the demographic information of the participants and patterns of substance use in the scene. It also collected the demand for consulting services and personal assessments on the usefulness of prospective and existing prevention programs and offers. <b><i>Results:</i></b> The study participants were 29 years old (SD 7.5); 43% were female. Alcohol is the most common substance in the party scene, followed by cannabis, MDMA/Ecstasy, amphetamine, cocaine, and ketamine. In this particular cohort, methamphetamine and “legal highs” did not play a major role. The most demanded preventive measure was more education about drugs and the so called drug-checking. <b><i>Conclusions:</i></b> Prevention in this area is both needed and requested, and an expansion of the existing programs (e.g., by so far politically controversial drug-checking) should be considered.

<b><i>Objectives:</i></b> Drug checking as a tool for harm reduction is offered in certain cities throughout Europe, the USA, and Australia, but in general, it is internationally still scarcely available and controversially discussed. This study aimed at investigating the potential impact of a drug-checking offer on Berlin nightlife attendees’ illicit drug use and at identifying the encouraging and discouraging factors for using or refraining from such an offer. <b><i>Methods:</i></b> Using an online questionnaire, we conducted a cross-sectional survey in a Berlin party scene. A total of 719 people participated in the survey that took part in 2019. <b><i>Results:</i></b> The vast majority of participants (92%) stated that they would use drug checking, if existent. If the test revealed the sample to contain a high amount of active ingredient, 91% indicated to take less of the substance than usual. Two-thirds (66%) would discharge the sample if it contained an unexpected/unwanted agent along with the intended substance. If the sample contained only unexpected/unwanted substances and not the intended substance at all, 93% stated to discharge the sample. Additional brief counseling was stated to be useful. Participants showed a comparatively high substance use. <b><i>Conclusions:</i></b> Drug checking as a harm reduction tool was highly accepted in the scene, and the majority of participants stated to align their consumption behavior accordingly, in a reasonable manner. A concomitant consultation would be appreciated, which may be used to direct educational information about harms and risks to users.