Healing the Past by Nurturing the Future: trauma-aware, healing-informed care to improve support for Aboriginal and Torres Strait Islander families - implementation and evaluation study protocol.

INTRODUCTION: Complex trauma can have serious impacts on the health and well-being of Aboriginal and Torres Strait Islander families. The perinatal period represents a 'critical window' for recovery and transforming cycles of trauma into cycles of healing. The Healing the Past by Nurturing the Future (HPNF) project aims to implement and evaluate a programme of strategies to improve support for Aboriginal and Torres Strait islander families experiencing complex trauma. METHOD: The HPNF programme was codesigned over 4 years to improve awareness, support, recognition and assessment of trauma. Components include (1) a trauma-aware, healing-informed training and resource package for service providers; (2) trauma-awareness resources for parents; (3) organisational readiness assessment; (4) a database for parents and service providers to identify accessible and appropriate additional support and (5) piloting safe recognition and assessment processes. The programme will be implemented in a large rural health service in Victoria, Australia, over 12 months. Evaluation using a mixed-methods approach will assess feasibility, acceptability, cost, effectiveness and sustainability. This will include service user and provider interviews; service usage and cost auditing; and an administrative linked data study of parent and infant outcomes. ANALYSIS: Qualitative data will be analysed using reflexive thematic analysis. Quantitative and service usage outcomes will be described as counts and proportions. Evaluation of health outcomes will use interrupted time series analyses. Triangulation of data will be conducted and mapped to the Consolidated Framework for Implementation Research and Reach, Effectiveness, Adoption, Implementation and Maintenance frameworks to understand factors influencing feasibility, acceptability, effectiveness, cost and sustainability. ETHICS AND DISSEMINATION: Approval granted from St Vincent's Melbourne Ethics Committee (approval no. 239/22). Data will be disseminated according to the strategy outlined in the codesign study protocol, in-line with the National Health and Medical Research Council Aboriginal and Torres Strait Islander Research Excellence criteria.

Using social media to recruit research participants: a literature review.

BACKGROUND: It may be challenging for researchers to recruit enough participants to have a diverse and representative sample for their studies. Usual recruitment methods that were historically effective can be difficult to use because of high costs, time constraints and geographical limitations. Social media is a low-cost, time-saving alternative. AIM: To summarise the benefits and challenges of using social media for recruitment. DISCUSSION: This article provides an overview of social media. It considers the advantages of social media for recruitment, including its cost-effectiveness, accessibility, speed and potential exposure for researchers. It also discusses the challenges of using social media for recruitment, including ethical ambiguity, homogenous sampling and questionable validity of information gathered. CONCLUSION: Using social media for research saves time and reduces costs, increasing access to hard-to-reach populations and the reach of recruitment efforts. IMPLICATIONS FOR PRACTICE: Options for researchers wishing to use social media for study recruitment are outlined, as are strategies for managing some of the challenges involved in this recruitment method.

Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.

Cell signaling is central to neuronal activity and its dysregulation may lead to neurodegeneration and cognitive decline. Here, we show that selective genetic potentiation of neuronal ERK signaling prevents cell death in vitro and in vivo in the mouse brain, while attenuation of ERK signaling does the opposite. This neuroprotective effect mediated by an enhanced nuclear ERK activity can also be induced by the novel cell penetrating peptide RB5. In vitro administration of RB5 disrupts the preferential interaction of ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates ERK1/2 nuclear translocation, and enhances global ERK activity. Importantly, RB5 treatment in vivo promotes neuroprotection in mouse models of Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) disease, and enhances ERK signaling in a human cellular model of HD. Additionally, RB5-mediated potentiation of ERK nuclear signaling facilitates synaptic plasticity, enhances cognition in healthy rodents, and rescues cognitive impairments in AD and HD models. The reported molecular mechanism shared across multiple neurodegenerative disorders reveals a potential new therapeutic target approach based on the modulation of KPNA2-ERK1/2 interactions.

Interventions from pregnancy to two years after birth for parents experiencing complex post-traumatic stress disorder and/or with childhood experience of maltreatment.

BACKGROUND: Acceptable, effective and feasible support strategies (interventions) for parents experiencing complex post-traumatic stress disorder (CPTSD) symptoms or with a history of childhood maltreatment may offer an opportunity to support parental recovery, reduce the risk of intergenerational transmission of trauma and improve life-course trajectories for children and future generations. However, evidence relating to the effect of interventions has not been synthesised to provide a comprehensive review of available support strategies. This evidence synthesis is critical to inform further research, practice and policy approaches in this emerging area. OBJECTIVES: To assess the effects of interventions provided to support parents who were experiencing CPTSD symptoms or who had experienced childhood maltreatment (or both), on parenting capacity and parental psychological or socio-emotional wellbeing. SEARCH METHODS: In October 2021 we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, together with checking references and contacting experts to identify additional studies. SELECTION CRITERIA: All variants of randomised controlled trials (RCTs) comparing any intervention delivered in the perinatal period designed to support parents experiencing CPTSD symptoms or with a history of childhood maltreatment (or both), to any active or inactive control. Primary outcomes were parental psychological or socio-emotional wellbeing and parenting capacity between pregnancy and up to two years postpartum. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials for inclusion, extracted data using a pre-designed data extraction form, and assessed risk of bias and certainty of evidence. We contacted study authors for additional information as required. We analysed continuous data using mean difference (MD) for outcomes using a single measure, and standardised mean difference (SMD) for outcomes using multiple measures, and risk ratios (RR) for dichotomous data. All data are presented with 95% confidence intervals (CIs). We undertook meta-analyses using random-effects models. MAIN RESULTS: We included evidence from 1925 participants in 15 RCTs that investigated the effect of 17 interventions. All included studies were published after 2005. Interventions included seven parenting interventions, eight psychological interventions and two service system approaches. The studies were funded by major research councils, government departments and philanthropic/charitable organisations. All evidence was of low or very low certainty. Parenting interventions Evidence was very uncertain from a study (33 participants) assessing the effects of a parenting intervention compared to attention control on trauma-related symptoms, and psychological wellbeing symptoms (postpartum depression), in mothers who had experienced childhood maltreatment and were experiencing current parenting risk factors. Evidence suggested that parenting interventions may improve parent-child relationships slightly compared to usual service provision (SMD 0.45, 95% CI -0.06 to 0.96; I2 = 60%; 2 studies, 153 participants; low-certainty evidence). There may be little or no difference between parenting interventions and usual perinatal service in parenting skills including nurturance, supportive presence and reciprocity (SMD 0.25, 95% CI -0.07 to 0.58; I2 = 0%; 4 studies, 149 participants; low-certainty evidence). No studies assessed the effects of parenting interventions on parents' substance use, relationship quality or self-harm. Psychological interventions Psychological interventions may result in little or no difference in trauma-related symptoms compared to usual care (SMD -0.05, 95% CI -0.40 to 0.31; I2 = 39%; 4 studies, 247 participants; low-certainty evidence). Psychological interventions may make little or no difference compared to usual care to depression symptom severity (8 studies, 507 participants, low-certainty evidence, SMD -0.34, 95% CI -0.66 to -0.03; I2 = 63%). An interpersonally focused cognitive behavioural analysis system of psychotherapy may slightly increase the number of pregnant women who quit smoking compared to usual smoking cessation therapy and prenatal care (189 participants, low-certainty evidence). A psychological intervention may slightly improve parents' relationship quality compared to usual care (1 study, 67 participants, low-certainty evidence). Benefits for parent-child relationships were very uncertain (26 participants, very low-certainty evidence), while there may be a slight improvement in parenting skills compared to usual care (66 participants, low-certainty evidence). No studies assessed the effects of psychological interventions on parents' self-harm. Service system approaches One service system approach assessed the effect of a financial empowerment education programme, with and without trauma-informed peer support, compared to usual care for parents with low incomes. The interventions increased depression slightly (52 participants, low-certainty evidence). No studies assessed the effects of service system interventions on parents' trauma-related symptoms, substance use, relationship quality, self-harm, parent-child relationships or parenting skills. AUTHORS' CONCLUSIONS: There is currently a lack of high-quality evidence regarding the effectiveness of interventions to improve parenting capacity or parental psychological or socio-emotional wellbeing in parents experiencing CPTSD symptoms or who have experienced childhood maltreatment (or both). This lack of methodological rigour and high risk of bias made it difficult to interpret the findings of this review. Overall, results suggest that parenting interventions may slightly improve parent-child relationships but have a small, unimportant effect on parenting skills. Psychological interventions may help some women stop smoking in pregnancy, and may have small benefits on parents' relationships and parenting skills. A financial empowerment programme may slightly worsen depression symptoms. While potential beneficial effects were small, the importance of a positive effect in a small number of parents must be considered when making treatment and care decisions. There is a need for further high-quality research into effective strategies for this population.

"You Can't Replace That Feeling of Connection to Culture and Country": Aboriginal and Torres Strait Islander Parents' Experiences of the COVID-19 Pandemic.

This Aboriginal-led study explores Aboriginal and Torres Strait Islander parents' experiences of COVID-19. 110 Aboriginal and Torres Strait Islander parents were interviewed between October 2020 and March 2022. Participants were recruited through community networks and partner health services in South Australia, Victoria, and Northern Territory, Australia. Participants were predominantly female (89%) and based in Victoria (47%) or South Australia (45%). Inductive thematic analysis identified three themes: (1) Changes to daily living; (2) Impact on social and emotional wellbeing; and (3) Disconnection from family, community, and culture. COVID-19 impacted Aboriginal and Torres Strait Islander families. Disruption to cultural practice, and disconnection from country, family, and community was detrimental to wellbeing. These impacts aggravated pre-existing inequalities and may continue to have greater impact on Aboriginal and Torres Strait Islander parents and communities due to intergenerational trauma, stemming from colonisation, violence and dispossession and ongoing systemic racism. We advocate for the development of a framework that ensures an equitable approach to future public health responses for Aboriginal and Torres Strait Islander people.

A Culturally Responsive Trauma-Informed Public Health Emergency Framework for Aboriginal and Torres Strait Islander Communities in Australia, Developed during COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic impacted peoples' livelihoods and mental wellbeing. Aboriginal and Torres Strait Islander peoples in Australia continue to experience intergenerational trauma associated with colonization and may experience trauma-related distress in response to government responses to public health emergencies. We aimed to develop a culturally responsive trauma-informed public health emergency response framework for Aboriginal and Torres Strait Islander peoples. This Aboriginal and Torres Strait Islander-led study involved: (i) a review of trauma-informed public health emergency responses to develop a draft framework (ii) interviews with 110 Aboriginal and Torres Strait Islander parents about how COVID-19 impacted their lives, and (iii) a workshop with 36 stakeholders about pandemic experiences using framework analysis to refine a culturally responsive trauma-informed framework. The framework included: an overarching philosophy (cultural humility, safety and responsiveness); key enablers (local leadership and Eldership); supporting strategies (provision of basic needs and resources, well-functioning social systems, human rights, dignity, choice, justice and ethics, mutuality and collective responsibility, and strengthening of existing systems); interdependent core concepts (safety, transparency, and empowerment, holistic support, connectedness and collaboration, and compassion, protection and caring); and central goals (a sense of security, resilience, wellbeing, self- and collective-efficacy, hope, trust, resilience, and healing from grief and loss).

Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.

LIM domain kinases 1 and 2 (LIMK1 and LIMK2) regulate actin dynamics and subsequently key cellular functions such as proliferation and migration. LIMK1 and LIMK2 phosphorylate and inactivate cofilin leading to increased actin polymerization. As a result, LIMK inhibitors are emerging as a promising treatment strategy for certain cancers and neurological disorders. High-quality chemical probes are required if the role of these kinases in health and disease is to be understood. To that end, we report the results of a comparative assessment of 17 reported LIMK1/2 inhibitors in a variety of in vitro enzymatic and cellular assays. Our evaluation has identified three compounds (TH-257, LIJTF500025, and LIMKi3) as potent and selective inhibitors suitable for use as in vitro and in vivo pharmacological tools for the study of LIMK function in cell biology.

A toolkit for the identification of NEAT1_2/paraspeckle modulators.

Paraspeckles are ribonucleoprotein granules assembled by NEAT1_2 lncRNA, an isoform of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1). Dysregulation of NEAT1_2/paraspeckles has been linked to multiple human diseases making them an attractive drug target. However currently NEAT1_2/paraspeckle-focused translational research and drug discovery are hindered by a limited toolkit. To fill this gap, we developed and validated a set of tools for the identification of NEAT1_2 binders and modulators comprised of biochemical and cell-based assays. The NEAT1_2 triple helix stability element was utilized as the target in the biochemical assays, and the cellular assay ('ParaQuant') was based on high-content imaging of NEAT1_2 in fixed cells. As a proof of principle, these assays were used to screen a 1,200-compound FDA-approved drug library and a 170-compound kinase inhibitor library and to confirm the screening hits. The assays are simple to establish, use only commercially-available reagents and are scalable for higher throughput. In particular, ParaQuant is a cost-efficient assay suitable for any cells growing in adherent culture and amenable to multiplexing. Using ParaQuant, we identified dual PI3K/mTOR inhibitors as potent negative modulators of paraspeckles. The tools we describe herein should boost paraspeckle studies and help guide the search, validation and optimization of NEAT1_2/paraspeckle-targeted small molecules.

Moral Injury, Chaplaincy and Mental Health Provider Approaches to Treatment: A Scoping Review.

The aim of this research was to describe the evidence examining the approaches taken by mental health providers (MHPs) and chaplains to address symptoms related to moral injury (MI) or exposure to potentially morally injurious events (PMIEs). This research also considers the implications for a holistic approach to address symptoms related to MI that combines mental health and chaplaincy work. A scoping review of literature was conducted using Medline, PsycINFO, Embase, Central Register of Controlled Trials, Proquest, Philosphers Index, CINAHL, SocINDEX, Academic Search Complete, Web of Science and Scopus databases using search terms related to MI and chaplaincy approaches or psychological approaches to MI. The search identified 35 eligible studies: 26 quantitative studies and nine qualitative studies. Most quantitative studies (n = 33) were conducted in military samples. The studies examined interventions delivered by chaplains (n = 5), MHPs (n = 23) and combined approaches (n = 7). Most studies used symptoms of post-traumatic stress disorder (PTSD) and/or depression as primary outcomes. Various approaches to addressing MI have been reported in the literature, including MHP, chaplaincy and combined approaches, however, there is currently limited evidence to support the effectiveness of any approach. There is a need for high quality empirical studies assessing the effectiveness of interventions designed to address MI-related symptoms. Outcome measures should include the breadth of psychosocial and spiritual impacts of MI if we are to establish the benefits of MHP and chaplaincy approaches and the potential incremental value of combining both approaches into a holistic model of care.

Social Anxiety Symptoms in Survivors of Childhood and Adolescent Cancer.

Purpose: Adolescent and young adult (AYA) cancer survivors may be at risk of developing symptoms of social anxiety disorder (SAD) due to disruptions in social participation and functioning following a cancer diagnosis. This study aimed to explore (1) the proportion of Australian AYA-aged survivors of childhood and adolescent cancer who experience symptoms of SAD, (2) how symptoms of SAD are described by survivors as affecting their daily social functioning. Methods: A mixed-methods cross-sectional design was employed, inviting survivors, aged 13-25 years, who had completed treatment between one and ten years ago. Survivors completed a paper-based questionnaire, containing validated measures of SAD, and an optional semistructured interview assessing current social functioning and social anxiety. Results: Twenty-seven survivors aged 13-25 years participated (M = 19.15, 51.9% male, and 7 years post-treatment). Nine (33%) participants reported clinically significant symptoms of SAD. In interviews, survivors reported worries about how others perceived them and fears around meeting new people. Survivors described that this impacted their daily social functioning, leading them to avoid, or endure with distress, feared social situations. Conclusion: This study shows that clinically significant social anxiety may be a concern for a subset of survivors of childhood/adolescent cancer. Identifying which young people are at risk of SAD after cancer and how best to support this vulnerable cohort is critical.

Best Practice Injury Compensation Processes Following Intentional Vehicular Assaults and Other Large Scale Transport Incidents: A Delphi Review.

OBJECTIVE: Intentional vehicular assaults on civilians have become more frequent worldwide, with some resulting in mass casualties, injuries, and traumatized witnesses. Health care costs associated with these vehicular assaults usually fall to compensation agencies. There is, however, little guidance around how compensation agencies should respond to mental and physical injury claims arising from large-scale transport incidents. METHODS: A Delphi review methodology was used to establish expert consensus recommendations on the major components of "no fault" injury claim processes for mental and physical injury. RESULTS: Thirty-three international experts participated in a 3-round online survey to rate their agreement on key statements generated from the literature. Consensus was achieved for 45 of 60 (75%) statements, which were synthesized into 36 recommendations falling within the domains of (1) facilitating claims, (2) eligibility rules, (3) payments and benefits for clients, (4) claims management procedures, (5) making and explaining decisions, (6) support and information resources for clients, (7) managing scheme staff and organizational response, (8) clients with special circumstances, and (9) scheme values and integrity. CONCLUSIONS: The recommendations present an opportunity for agencies to review their existing claims management systems and procedures. They also provide the basis for the development of best practice guidelines, which may be adapted for application to compensation schemes in different contexts worldwide.

Characterization of DNA Methylomic Signatures in Induced Pluripotent Stem Cells During Neuronal Differentiation.

In development, differentiation from a pluripotent state results in global epigenetic changes, although the extent to which this occurs in induced pluripotent stem cell-based neuronal models has not been extensively characterized. In the present study, induced pluripotent stem cell colonies (33Qn1 line) were differentiated and collected at four time-points, with DNA methylation assessed using the Illumina Infinium Human Methylation EPIC BeadChip array. Dynamic changes in DNA methylation occurring during differentiation were investigated using a data-driven trajectory inference method. We identified a large number of Bonferroni-significant loci that showed progressive alterations in DNA methylation during neuronal differentiation. A gene-gene interaction network analysis identified 60 densely connected genes that were influential in the differentiation of neurons, with STAT3 being the gene with the highest connectivity.

Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons.

Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the earliest stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age. It has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, we developed the fetal brain clock (FBC), a bespoke epigenetic clock trained in human prenatal brain samples in order to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons. The FBC was tested in two independent validation cohorts across a total of 194 samples, confirming that the FBC outperforms other established epigenetic clocks in fetal brain cohorts. We applied the FBC to DNA methylation data from iPSCs and embryonic stem cells and their derived neuronal precursor cells and neurons, finding that these cell types are epigenetically characterized as having an early fetal age. Furthermore, while differentiation from iPSCs to neurons significantly increases epigenetic age, iPSC-neurons are still predicted as being fetal. Together our findings reiterate the need to better understand the limitations of existing epigenetic clocks for answering biological research questions and highlight a limitation of iPSC-neurons as a cellular model of age-related diseases.

Preventing the onset of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a common mental health condition that requires exposure to a traumatic event. This provides unique opportunities for prevention that are not available for other disorders. The aim of this review was to undertake a systematic review and evaluation of randomized controlled trials (RCTs) of interventions designed to prevent PTSD in adults. Searches involving Cochrane, Embase, Medline, PsycINFO, PILOTS and Pubmed databases were undertaken to identify RCTs of pre-incident preparedness and post-incident interventions until May 2019. Six pre-incident and 69 post-incident trials were identified that could be included in meta-analyses. The overall quality of the evidence was low. There was emerging evidence that some interventions may be helpful but an absence of evidence for any intervention that can be strongly recommended for universal, selected or indicated prevention before or within the first three months of a traumatic event. The strongest results were found for cognitive-behavioural therapy with a trauma focus (CBT-T) in individuals with a diagnosis of acute stress disorder which supports calls to detect and treat individuals with significant symptoms rather than providing blanket preventative interventions. Further research is required to optimally configure existing interventions with some evidence of effect and to develop novel interventions to address this major public health issue.

Attack, flare-up, or exacerbation? The terminology preferences of patients with severe asthma.

Background: People with severe asthma experience frequent life-threatening acute asthma events. A Lancet commission recently highlighted that terms "exacerbations" and "flare-ups" are seen to trivialize these episodes and recommended use of the term "attacks." Clinicians however, preferentially use the term "exacerbation" and some guidelines recommend the use of "exacerbation" with patients.Objective: This descriptive qualitative study aimed to understand the patient's experience and perspectives of these events and language used to describe them.Methods: Semi-structured one-on-one interviews were conducted in Australia and the UK in 18 people with severe asthma and 10 with mild-moderate asthma regarding their usage and preferences for such terminologies. Additionally, nine people with severe asthma participated in two focus groups in which use of preferred terminology was explored.Results: Mean age of participants was 57 ± 14.03 yr and 65% were female. A total 67 quotes were recorded in which 16 participants with severe asthma spontaneously used either the term "attack," "flare-up" and/or "exacerbation." Of these quotes, all 16 participants used "attack," one used all three terms and two used both "exacerbation" and "attack." The term "attack" was used to describe frightening events having major impacts on participant's lives, whereas "exacerbation" and "flare-up" were used to refer to both severe and mild, transient asthma-related events.Conclusion: Usage of the term "attack" was preferred by patients with severe asthma. Adoption of this language may assist in patient-clinician communication and disease management and outcomes. Wider stakeholder engagement is needed to confirm this suggestion. AbbreviationsFEV1forced expiratory volume in 1 secondATSAmerican Thoracic SocietyERSEuropean Respiratory SocietyACQAsthma Control QuestionnaireICSinhaled corticosteroidsOCSoral corticosteroidsBTSBritish Thoracic SocietySIGNScottish Intercollegiate Guidelines NetworkWAPwritten action plan.

Detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and iPSC-derived neurons.

Good's buffers are commonly used for cell culture and, although developed to have minimal to no biological impact, they cause alterations in cellular processes such as autophagy and lysosomal enzyme activity. Using Chinese hamster ovary cells and induced pluripotent stem cell-derived neurons, this study explores the effect of zwitterionic buffers, specifically HEPES, on lysosomal volume and Ca2+ levels. Certain zwitterionic buffers lead to lysosomal expansion and reduced lysosomal Ca2+. Care should be taken when selecting buffers for growth media to avoid detrimental impacts on lysosomal function.

Health-related quality of life burden in severe asthma.

It is largely unrecognised that the impacts of asthma are different in patients with severe disease compared with patients with mild to moderate disease. Severe asthma is associated with a significant health-related quality of life (HRQoL) burden due to excessive symptoms, frequent and life-threatening attacks, increased comorbidity burden, and high pharmacological treatment requirements. Interventions aimed at improving HRQoL need to be specifically tested in populations with severe asthma, including multicomponent interventions targeting the many clinical characteristics associated with the disease. It is necessary to have patient-reported outcome measures developed specifically for severe asthma. Public health messages recognising the significant burden of severe asthma on quality of life are needed.

Age-dependent Disturbances of Neuronal and Glial Protein Expression Profiles in Areas of Secondary Neurodegeneration Post-stroke.

Despite the fact that approximately 80% of strokes occur in those aged over 60 years, many pre-clinical stroke studies have been conducted in younger adult rodents, raising debate about translation and generalizability of these results. We were interested in potential age differences in stroke-induced secondary neurodegeneration (SND). SND involves the death of neurons in areas remote from, but connected to, the site of infarction, as well as glial disturbances. Here we investigated potential differences in key parameters of SND in the thalamus, a major site of post-stroke SND. Protein expression profiles in young adult (2-4 months) and aged (22-23 months) mice were analyzed 28 days after a cortical stroke. Our results show that age reduced the expression of synaptic markers (PSD 95, Synapsin1) and increased Amyloid ß oligomer accumulation after stroke. Protein expression of several markers of glial activity remained relatively stable across age groups post-stroke. We have identified that age exacerbates the severity of SND after stroke. Our results, however, do not support a view that microglia or astrocytes are the main contributors to the enhanced severity of SND in aged mice.