Thrombolytic therapy based on lyophilized platelet-derived nanocarriers for ischemic stroke.

BACKGROUND: Intravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice. RESULTS: Cellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response. CONCLUSIONS: This study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups.

Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham group is usually not included in the experimental design of these studies. In this study, we aimed to evaluate the relevance of the sham group by analyzing and comparing the brain protein profiles of the sham and MCAO groups. In the sham group, 98 dysregulated proteins were detected, compared to 171 in the ischemic group. Moreover, a comparative study of protein profiles revealed the existence of a pool of 57 proteins that appeared to be dysregulated in both sham and ischemic animals. These results indicated that the surgical procedure required for the intraluminal occlusion of the middle cerebral artery (MCA) induces changes in brain protein expression that are not associated with ischemic lesions. This study highlights the importance of including sham control groups in the experimental design, to ensure that surgical intervention does not affect the therapeutic target under study.

Psychometric properties of the Spanish version of the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM) in Chile.

OBJECTIVE: To examine the psychometric properties of the Spanish version of the 34-item Clinical Outcomes in Routine Evaluation-Outcome Measure questionnaire (CORE-OM). METHOD: Psychometric exploration was conducted in two samples: non-clinical (n = 706) and clinical (n = 420) participants. The non-clinical sample comprised a subgroup of community members (n = 308) and students (n = 398). The clinical sample consisted of self-reported patients (n = 209) and outpatients (n = 211). The analysis included both internal and test-retest reliability, convergent validity, and principal component analysis. A reliable change index and clinical cut-off scores were established for assessing clinically significant change. RESULTS: The Spanish CORE-OM demonstrated good internal consistency and test-retest reliability, along with satisfactory convergent validity against the 45-item Outcome Questionnaire (OQ-45.2). There were strong differentiations between the clinical and non-clinical samples and the four sample subsets. The outpatient group reported the highest scores, while the community group exhibited the lowest scores. There were no marked gender effects. All observed patterns aligned closely with the established Spanish referential data. CONCLUSION: Our findings provide support for the utilization of the Spanish CORE-OM as a measure for tracking psychotherapeutic progress in the context of Chile.

Routine Outcome Monitoring from Psychotherapists' Perspectives: A Framework Analysis Study of Expected Benefits and Difficulties.

Psychotherapists' attitudes and expectations towards routine outcome monitoring can impact the likelihood of its fruitful implementation. While existing studies have predominantly focused on Europe and North America, research in Latin America remains limited. The aim of this study is to explore therapists' expected benefits and difficulties prior to implementing a routine outcome monitoring system in a university psychotherapy service in Ecuador. An exploratory and descriptive cross-sectional qualitative study was carried out with 20 participants aged 21 to 47. Semi-structured interviews were conducted to explore participants' knowledge about routine outcome monitoring, their expectations of the difficulties, benefits, usability and risks of using a monitoring system, as well as their expectations about their role in the process. The data analysis adhered to the framework analysis methodology, leading to the identification of six overarching themes, 36 specific themes and 82 subthemes. The interviews highlighted a spectrum of positive and negative expectations at several levels: institutional/general, therapeutic process, therapists, and clients. Perceived benefits encompassed various aspects, including the availability of supplementary information, continuous adaptation of the therapeutic process, facilitation of organization and treatment planning, opportunities for professional development, and fostering patient trust and empowerment. On the other hand, anticipated difficulties comprised concerns such as discomfort among therapists and clients, increased workload, system usage and technical difficulties, and the risk of excessive quantification. Overall, participants expressed more anticipated benefits than difficulties. We present recommendations that can support and optimize the current local implementation efforts of routine outcome monitoring, both within this service and in other settings. These recommendations consider ways to meet positive expectations and address or mitigate negative ones.

The Importance of Conducting Practice-oriented Research with Underserved Populations.

There has been a growing emphasis on dissemination of empirically supported treatments. Dissemination, however, should not be restricted to treatment. It can and, in the spirit of the scientific-practitioner model, should also involve research. Because it focuses on the investigation of clinical routine as it takes place in local settings and because it can involve the collaboration of several stakeholders, practice-oriented research (POR) can be viewed as an optimal research method to be disseminated. POR has the potential of addressing particularly relevant gaps of knowledge and action when implemented in regions of the world that have limited resources for or experiences with empirical research, and/or in clinical settings that are serving clinical populations who are not typically receiving optimal mental care services - specifically, individuals in rural and inner cities that have limited economic and social resources. The establishment and maintenance of POR in such regions and/or settings, however, come with specific obstacles and challenges. Integrating the experiences acquired from research conducted in various continents (Africa, Europe, Latin America, and North America), the goal of this paper is to describe some of these challenges, strategies that have been implemented to address them, as well as new possible directions to facilitate the creation and growth of POR. It also describes how these challenges and ways to deal with them can provide helpful lessons for already existing POR infrastructures.

The effect of two cognitive therapies on subjective wellbeing of individuals with depression: results from a randomised controlled trial.

BACKGROUND: Despite the burden associated to depression, current standards of care are still limited in scope and effectiveness. In addition, therapy outcomes have frequently focused solely on symptoms, leaving patients' wellbeing relatively unaddressed. AIMS: The objective of this study was to test whether two cognitive therapies increased subjective wellbeing in a sample of adults diagnosed with a depressive disorder, additionally assessing the relationship between this growth and decreases in both depression severity and psychological distress. METHODS: Data from 116 participants from a randomised controlled trial comparing the efficacy of cognitive behavioural therapy and dilemma-focused therapy were analysed. Multilevel linear models were employed, together with correlational analyses. RESULTS: Results showed that both interventions significantly improved wellbeing with moderate to large effect sizes, while no significant differences were found between treatments. In turn, the increase in wellbeing was significantly associated to improvements in depression severity and psychological distress. CONCLUSIONS: This study sheds light on the complex relationship between happiness and depression, supporting their conceptualisation as related yet independent human experiences, and strengthening subjective wellbeing as a useful outcome for psychological research. Psychotherapy is presented as an effective intervention to enhance wellbeing, even among individuals with severe depressive symptoms.

Sonosensitive capsules for brain thrombolysis increase ischemic damage in a stroke model.

BACKGROUND: Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model. RESULTS: In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke. CONCLUSIONS: This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans.

Geosocial Networking Apps Use Among Sexual Minority Men in Ecuador: An Exploratory Study.

Geosocial networking applications (GSN apps) have become important socialization contexts for sexual minority men (SMM). Despite their popularity, there is limited research carried out in Latin American countries and no single previous study done in Ecuador. To fill this gap, this exploratory study described and analyzed the relationships between the sociodemographic characteristics of SMM using GSN apps, their sought and fulfilled expectations, profile shared and sought characteristics, and the evaluation of their experiences as users including their perceptions of support, and discrimination. We used an online recruited sample of 303 participants enrolled between November 2019 and January 2020. Most respondents used Grindr and reported spending up to 3 h per day using apps. Most common sought expectations were getting distracted, meeting new friends, and meeting people for sexual encounters. The least met expectation was meeting someone to build a romantic relationship with. When asked about their profiles, participants reported sharing mainly their age, photographs, and sexual role. Participants also prioritized these characteristics when looking at others' profiles. When asked about their experiences, most reported having been discriminated against, weight being the main reason for it. Some participants also indicated having received emotional support from other users. Correlation analyses indicated significant but weak relationships among the variables. Results indicated a positive correlation between time as an active GSN app user and higher experiences of discrimination. Likewise, higher number of used apps related positively with levels of received support. These results provide information that could inform future research in the country and the region regarding GSN apps use among SMM, socialization practices, and modern dating tools.

Sexual Behaviors and HIV/STI Prevention Strategies Among Sexual Minority Men in Ecuador Who Use Geosocial Networking Apps.

Around the world, geosocial networking apps have become widely popular among sexual minority men (SMM). This research analyzed the sexual behaviors and HIV and STI prevention strategies (HIV/STI testing, HIV/STI inquiry, and HIV/STI disclosure) of an online-recruited sample of 284 SMM living in Ecuador. Sexting and oral sex were the most common sexual behaviors among SMM in the sample. Most participants had low perceptions of HIV and STI risk; 85% reported being tested for HIV and 70% for STIs. Being older predicted higher odds of being tested for either HIV or STIs at least once. Being single also predicted HIV testing. Future interventions in the country should explore apps' utility as intervention tools to spread information about sexual health and HIV prevention strategies, such as condom use and event-driven PrEP. Apps can also facilitate connections to sexual health services, including programs for PrEP initiation and linkage to HIV treatment. They should also focus on promoting sexual harm reduction conversations among potential app-met sexual partners.

Acceptability and Psychometric Properties of the Spanish Translation of the Schwartz Outcome Scale-10 (SOS-10-E) Outside the United States: A Replication and Extension in a Latin American Context.

The Schwartz Outcome Scale-10 is a 10-item measure that has proven utility for assessing well-being and mental health and measuring change over time. Although there is a Spanish translation of the measure created in the United States for the Latino population, its acceptability and psychometric properties have not been studied in unilingual Spanish speakers, nor outside the United States. The aim of the present study is to explore these properties in larger samples, clinical and non-clinical, from Latin America adding convergent validity checking and exploration of effects of gender and age on scores. A qualitative study was conducted with 11 participants to test for dialect/language issues, then a psychometric exploration of data from 886 participants in a non-clinical sample and 172 in a clinical sample. The results showed good psychometric characteristics and suggest that the SOS-10-E can be used in Latin America. A cutoff of 42.51 differentiates clinical scores from non-clinical. Future studies are needed to explore sensitivity to change and check replication in other Spanish speaking populations.

Psychological intervention change measurement in Latin America: Where from? Where to?

Objective: To conduct a scoping review of measure utilization in Latin America. We relate the findings to the needs of the region and give recommendations for measure usage in LA. Methods: Six electronic databases (PubMed, Web of Science, CINAHL, PsychInfo, SCOPUS, and SCIELO) were searched to identify peer-reviewed literature. In total, 207 studies using change and/or outcome measures were identified based on a priori inclusion criteria. Results: Production by country varied markedly; more than three quarters of the studies took place in just three of the 20 Latin American countries: Brazil, Chile, and Mexico. The most frequently used measures were the Outcome Questionnaire, Beck Depression Inventory-II, Hamilton Rating Scale, and Yale-Brown Obsessive-Compulsive Scale. The most common diagnosis was depression (n = 54). Conclusions: Outcome and change research in Latin America is growing rapidly but future efforts should focus more tightly on the needs of the region, as well as on forging collaborations with researchers from other regions. The use of change measures for serial assessment throughout interventions is recommended in view of its adaptability to highly diverse Latin American social realities. Dissemination of research findings and promotion of outcome and change measure use through implementation of public policy is recommended.

A Nationwide Study of Incidence and Mortality Due to Traumatic Brain Injury in Ecuador (2004-2016).

OBJECTIVE: Traumatic brain injury (TBI) is a public health problem worldwide. Information regarding TBI from low- and middle-income countries is scarce. The objectives of this study are to determine the incidence, mortality and geodemographic distribution of TBI in Ecuador. METHODS: A population-based analytical study from 2004 to 2016 was conducted in Ecuador. Men and women with a diagnosis of TBI from all ages (0-110 years) were included. Data was obtained from official hospital-discharges records and retrieved from the National Institute of Statistics and Census (INEC) Database. We analyzed data by region, province and canton with a monthly resolution. The incidence, mortality, case fatality rates and the risk of developing TBI within the population were calculated based on the last 13 years of available data. RESULTS: A total of 124,576 hospital admissions and 5,264 deaths due to TBI were registered in Ecuador from 2004 to 2016. The overall TBI-related hospital admission rate was 70.68 per 100,000. The sex- and age-specific rate was 90.1 per 100,000 for men and 64.1 per 100,000 for women. Mestizos' population has the highest adjusted incidence rate of 195.6 per 100,000, followed by the indigenous with 61.4 per 100,000 and Afro-Americans with 14.2 per 100,000. The overall annual mortality rate during the study ranged from 2.11 to 3.35 per 100,000. Case fatality rates were significantly higher in older populations, becoming fatal in up to 27% of men >90 years/old and in 15% of women older than 90 years/old. CONCLUSION: This is the first recorded epidemiological study of the socio-demographic distribution of TBI in Ecuador to date. The study found that young men were almost 4 times more likely to be hospitalized due to TBI than women of this age. Fatalities due to TBI were less likely to occur among younger age groups, increasing significantly among the elderly population. The national incidence rate of TBI has been decreasing since 2011, which coincides with the introduction of stricter alcohol regulation, suggesting that this measure might have played a role in this reduction.

Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke.

OBJECTIVE: Blood/brain-glutamate grabbing is an emerging concept in the treatment of acute ischemic stroke, where essentially the deleterious effects of glutamate after ischemia are ameliorated by coaxing glutamate to enter the bloodstream and thus reducing its concentration in the brain. Aiming to demonstrate the clinical efficacy of blood glutamate grabbers in patients with stroke, in this study, we resorted to a drug-repositioning strategy for the discovery of new glutamate-grabbing drugs. METHODS: The glutamate-grabbing ability of 1,120 compounds (90% of which were drugs approved by the US Food and Drug Administration) was evaluated during an in vitro high-throughput screening campaign. Subsequently, the protective efficacy of the selected drugs was probed in an ischemic animal model and finally tested in stroke patients. RESULTS: Riboflavin (vitamin B2 ) was identified as the main hit compound. In ischemic animal models treated with riboflavin (1mg/kg), it was confirmed that blood glutamate reduction was associated with a significant reduction of infarct size. These results led to a randomized, double-blind, phase IIb clinical trial with patients with stroke. Fifty patients were randomized to 1 of the 2 study arms: the control group (placebo) and the experimental group (20mg of riboflavin [vitamin B2 Streuli@ ). Decrease in glutamate concentration was significantly greater (p < 0.029) in the treated group. Comparative analysis of the percentage improvement on the National Institutes of Health Stroke Scale score at discharge was slightly higher in the riboflavin-treated group than in the placebo group (33.7 ± 43.7 vs 48.9 ± 42.4%, p = 0.050). INTERPRETATION: This translational study represents the first human demonstration of the efficacy of blood glutamate grabbers in the treatment of patients with stroke, paving the way for the development of a promising novel protective therapy. Ann Neurol 2018;84:260-273.

Cognitive conflict resolution during psychotherapy: Its impact on depressive symptoms and psychological distress.

OBJECTIVE: The aim of this study was to assess the resolution of cognitive conflicts (CCs) within a randomized controlled trial testing the differential efficacy of group cognitive behavioral therapy (CBT) plus an individually tailored intervention module focused on CCs vs. group plus individual CBT, and to determine whether CC resolution was related to improvement in symptoms and psychological distress. METHODS: The data come from 104 adults meeting criteria for major depressive disorder and/or dysthymia. Change in scores on the Beck Depression Inventory-II and Clinical Outcomes in Routine Evaluation-Outcome Measure was assessed at the end of treatment and at three-month follow-up. Outcomes were compared between those participants who resolved their CCs and those who maintained them using three-level multilevel growth models. RESULTS: CC resolution did not depend on treatment allocation. Participants who resolved their CCs acquired greater benefits with regards to reduction of depressive symptoms and psychological distress than those who maintained their conflicts. CONCLUSIONS: CC seems to be a relevant notion to take into consideration to understand symptom improvement. Further research on CC might lead to the advancement of treatments which involve conflict resolution as a change mechanism.

A DILEMMA-FOCUSED INTERVENTION FOR DEPRESSION: A MULTICENTER, RANDOMIZED CONTROLLED TRIAL WITH A 3-MONTH FOLLOW-UP.

BACKGROUND: Since long ago it has been asserted that internal conflicts are relevant to the understanding and treatment of mental disorders, but little research has been conducted to support the claim. The aim of this study was to test the differential efficacy of group cognitive behavioral therapy (CBT) plus an intervention focused on the dilemma(s) detected for each patient versus group individual CBT plus individual CBT for treating depression. A comparative controlled trial with a 3-month follow-up was conducted. METHODS: One hundred twenty-eight adults meeting criteria for MDD and/or dysthymia, presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct, assessed by the repertory grid technique) and who had completed seven sessions of group CBT were randomly assigned to eight sessions of individual manualized CBT or dilemma-focused therapy (DFT). The Beck Depression Inventory-II was administered at baseline, at the end of therapy and after 3 months' follow-up. RESULTS: Multilevel mixed effects modeling yielded no significant differences between CBT and DFT with the intention-to-treat sample. Equivalent effect sizes, remission, and response rates were found with completers as well. In combination with group CBT, both individual CBT and DFT significantly reduced depressive symptoms. CONCLUSIONS: Both conditions obtained comparable results to those in the literature. Thus, the superiority of the adjunctive DFT was not demonstrated. Working with dilemmas can be seen as a promising additional target in the psychotherapy of depression, but further research is still required.

Cognitive conflicts in major depression: between desired change and personal coherence.

OBJECTIVES: The notion of intrapsychic conflict has been present in psychopathology for more than a century within different theoretical orientations. However, internal conflicts have not received enough empirical attention, nor has their importance in depression been fully elaborated. This study is based on the notion of cognitive conflict, understood as implicative dilemma (ID), and on a new way of identifying these conflicts by means of the Repertory Grid Technique. Our aim was to explore the relevance of cognitive conflicts among depressive patients. DESIGN: Comparison between persons with a diagnosis of major depressive disorder and community controls. METHODS: A total of 161 patients with major depression and 110 non-depressed participants were assessed for presence of IDs and level of symptom severity. The content of these cognitive conflicts was also analysed. RESULTS: Repertory grid analysis indicated conflict (presence of ID/s) in a greater proportion of depressive patients than in controls. Taking only those grids with conflict, the average number of IDs per person was higher in the depression group. In addition, participants with cognitive conflicts displayed higher symptom severity. Within the clinical sample, patients with IDs presented lower levels of global functioning and a more frequent history of suicide attempts. CONCLUSIONS: Cognitive conflicts were more prevalent in depressive patients and were associated with clinical severity. Conflict assessment at pre-therapy could aid in treatment planning to fit patient characteristics.

Exploring healthcare barriers and satisfaction levels among deaf individuals in Ecuador: A video-based survey approach.

BACKGROUND: Approximately 80% of Deaf individuals live in low- and middle-income countries, where health systems often overlook their specific needs. This communication gap can result in misdiagnosis and inappropriate treatment, impacting their overall satisfaction with healthcare services. OBJECTIVES: This study aims to uncover barriers to healthcare access and preferences among the Deaf population in Ecuador, and the role of communication barriers in shaping satisfaction levels with healthcare services. METHODS: The study gathered data from 386 participants through online surveys, focusing on demographic characteristics, healthcare experiences, communication methods, and levels of satisfaction. Descriptive statistics and association analyses were employed to analyze the data. RESULTS: The study reveals that nearly all participants possessed an officially recognized disability (95.9%) and 53.9% reported hereditary deafness. Ecuadorian sign language was predominant (60.9%). Communication barriers were evident, with 65.0% having trouble understanding medical instructions, and 66.6% identifying a deficiency of tools for Deaf individuals in healthcare settings. Satisfaction levels were associated with the presence of interpreters during medical care, with 46.6% expressing a preference for interpreters over other communication methods. Additionally, private healthcare facilities were perceived as providing better services, despite being less frequently accessed (38.9%). Dissatisfaction was evident, particularly in aspects of communication and physician courtesy. CONCLUSIONS: This study underscores the importance of tailoring healthcare services to address the unique needs of the Deaf population. Communication barriers emerged as a central obstacle, necessitating the inclusion of sign language interpreters and improvement of resources. The study's implications extend to healthcare equity in developing nations, emphasizing the significance of patient-centered care and inclusive healthcare practices.

New Perspectives in Neuroprotection for Ischemic Stroke.

The constant failure of new neuroprotective therapies for ischemic stroke has partially halted the search for new therapies in recent years, mainly because of the high investment risk required to develop a new treatment for a complex pathology, such as stroke, with a narrow intervention window and associated comorbidities. However, owing to recent progress in understanding the stroke pathophysiology, improvement in patient care in stroke units, development of new imaging techniques, search for new biomarkers for early diagnosis, and increasingly widespread use of mechanical recanalization therapies, new opportunities have opened for the study of neuroprotection. This review summarizes the main protective agents currently in use, some of which are already in the clinical evaluation phase. It also includes an analysis of how recanalization therapies, new imaging techniques, and biomarkers have improved their efficacy.

Modulation of Abundance and Location of High-Mobility Group Box 1 in Human Microglia and Macrophages under Oxygen-Glucose Deprivation.

While stroke represents one of the main causes of death worldwide, available effective drug treatment options remain limited to classic thrombolysis with recombinant tissue plasminogen activator (rtPA) for arterial-clot occlusion. Following stroke, multiple pathways become engaged in producing a vicious proinflammatory cycle through the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) and heat shock protein 70 kDa (HSP72). HMGB1, in particular, can activate proinflammatory cytokine production when acetylated (AcHMGB1), a form that prefers cytosolic localization and extracellular release. This study aimed at determining how HMGB1 and HSP72 are modulated and affected following treatment with the anti-inflammatory compound resveratrol and novel platelet membrane-derived nanocarriers loaded with rtPA (CSM@rtPA) recently developed by our group for ischemic artery recanalization. Under ischemic conditions of oxygen-glucose deprivation (OGD), nuclear abundance of HMGB1 and AcHMGB1 in microglia and macrophages decreased, whereas treatment with CSM@rtPA did not alter nuclear or cytosolic abundance. Resveratrol treatment markedly increased the cytosolic abundance of HSP72 in microglia. Using proximity ligation assays, we determined that HSP72 interacted with HMGB1 and with acetylated HMGB1. The interaction was differentially affected under the OGD conditions. Resveratrol treatment under the OGD further decreased HSP72-HMGB1 interactions, whereas, in contrast, treatment increased HSP72-AcHMGB1 interactions in microglia. This study points out a salient molecular interaction suited for a two-pronged nanotherapeutic intervention in stroke: enhancement of rtPA's thrombolytic activity and modulation of cytosolic interactions between HMGB1 and HSP72 by resveratrol.