Young Stroke Research Articles

Trajectories of intrusive and deliberate rumination in young and middle-aged stroke survivors: A growth mixture modeling approach.

This study aimed to explore the relationship between intrusive and deliberate rumination, to identify distinct trajectories of intrusive and deliberate rumination, and to examine their predictors in young and middle-aged stroke survivors. This study employed a longitudinal design in which 200 young and middle-aged stroke survivors were investigated at 1-week pre-discharge (T0), 1 month (T1), 3 months (T2), and 6 months (T3) post-discharge. The Event-Related Rumination Inventory, Simplified Coping Style Questionnaire, and Perceived Social Support Scale were used for data collection. The results showed that intrusive rumination was positively correlated with deliberate rumination at T0 and T1, and negatively correlated with deliberate rumination at T3. Growth mixture modeling identified three classes of intrusive rumination: Stable-low, Declined, and Elevated group, and two classes of deliberate rumination: High-level and Low-level group. Furthermore, number of children or dysfunctions, type of stroke, family history of stroke, negative coping, and social support were found to predict intrusive rumination. These findings can help healthcare providers timely intervene on survivors in the Elevated and Stable-low intrusive rumination groups, and the Low-level deliberate rumination group.

Incidence and influencing factors of post-stroke cognitive impairment in convalescent young patients with first-ever stroke

ObjectiveTo investigate the occurrence of post-stroke cognitive impairment (PSCI) and its influencing factors in convalescent young patients with first-ever stroke. MethodsA total of 300 first-ever young stroke patients (age ≤45 years) were collected. The Mini-Mental State Examination (MMSE) was used to assess the cognitive status. The sociodemographic data, clinical symptoms, social environment, and behavior-related information were collected and analyzed. ResultsThe incidence of PSCI in young stroke patients was 62.33 %. Through univariate analysis, there were statistical differences in different levels of education, smoking status and hypertension (P < 0.05). With subsequently multivariate logistic regression analysis, it was found that junior high school (OR=8.58,95 %CI:2.25∼32.70) and high school (OR=10.50,95 %CI:2.69∼41.00) education levels, lesion volume >3.00 cm3 (OR=8.03,95 %CI:2.28∼28.36), stroke in the frontal-parietal-temporal region (OR=7.26,95 %CI:1.58∼33.40) and the basal ganglia area (OR=6.13,95 %CI:1.24∼30.43), high NIHSS score (OR=1.17,95 %CI: 1.06∼1.29), and high diastolic blood pressure variability coefficient (OR=1.43,95 %CI: 1.02∼2.01) were risk factors for PSCI. Meanwhile, 24≤BMI<28 (OR=0.06,95 %CI:0.02∼0.23) and BMI<24 (OR=0.18,95 %CI:0.06∼0.53), hospitalization cost >20,000/month (OR=0.22,95 %CI:0.09∼0.56), and stroke onset in spring and summer (OR=0.37,95 %CI:0.14∼0.96) were protective factors. ConclusionThe incidence of PSCI is relatively high in young stroke patients. Junior high and high school education, stroke lesions >3.00cm3, strokes in the frontal-parietal-temporal and basal ganglia regions, high NIHSS scores, and high DBPV are risk factors for PSCI in young stroke patients. Meanwhile, BMI<28, treatment cost >20,000/month, and stroke onset in spring and summer are protective factors for PSCI in young stroke patients.

Stroke in young adults

Objective: Stroke is an important cause of morbidity and mortality in young adults especially in developing countries. This study aimed at reviewing epidemiology, types, etiologies, risk factors in the young adults in 108 Military Central Hospital. Subject and method: This study retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the 108 Military Central Hospital between February 1, 2022, and September 18, 2023 to analyze epidemiology, types, etiologies, risk factors, compare the age groups of 16-30 and 31-45 years. Result: Among 319 young stroke patients (mean age at onset 36.4 ± 8.1 years; male 71.5%), there were nontraumatic spontaneous hemorrhagic stroke (including 156 intracerebral hemorrhage (ICH) and 47 subarachnoid hemorrhage, (SAH)), 106 ischemic stroke and 10 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (63.2% vs 45.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (80.6%), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (57.1%). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, heart disease and cigarette smoking, excessive alcohol intake were more common risk factors for infarction than ICH. Conclusion: An aggressive approach to elucidate the etiology of stroke must be indicated for all young stroke patients. Structural vasculopathy was the most common etiology in patients aged 16-30, whereas hypertensive ICH was the most common in patients aged 31-45. For ischemic stroke, in addition to common causes such as cardiac embolism, atherosclerotic cerebrovascular disease... Other causes including arterial dissections, autoimmune diseases, moyamoya disease, cancer-related thromboembolisms, cerebral thrombosis venous complications, hematologic disease...

D-dimer levels in young patients with ischemic stroke: A clinical report

Objective: This clinical report investigates the role of D-dimer in young ischemic stroke patients and its association with stroke severity assessed by the National Institutes of Health Stroke Scale (NIHSS) and functional outcomes evaluated using the modified Rankin Scale (mRS). Subject and method: We conducted a prospective study on 35 young patients (aged under 46) diagnosed with acute ischemic stroke at 108 Military Central Hospital in Ha Noi from October 2022 to April 2023. Each patient underwent thorough clinical evaluation, including a detailed medical history, physical examination, and neuroimaging studies. D-dimer levels were measured within 24 hours of admission using standard laboratory assays. The patients were divided into 2 groups according to mRS scores or NIHSS scores evaluated on the first day inhospital. Result: We observed that plasma D-dimer level correlated significantly with the prognosis of acute cerebral infarction (ACI) evaluated based on both mRS scores (1526.58 ± 1462.51ng/mL for poor prognosis versus 348.22 ± 201.14ng/mL for good prognosis, p&lt;0.05) and NIHSS scores (1962.00 ± 1578.50ng/mL for poor prognosis versus 501.93 ± 663.10ng/mL for good prognosis, p&lt;0.05). Conclusion: Our results demonstrated that there is a significant correlation between elevated D-dimer levels and worsened functional outcomes and increased mortality in young patients with acute ischemic stroke.

What younger women stroke survivors need: Perspectives of health care professionals

What younger women stroke survivors need: Perspectives of health care professionals

Recurrent vascular events partially explain association between diabetes and poor prognosis in young ischemic stroke patients

Recurrent vascular events partially explain association between diabetes and poor prognosis in young ischemic stroke patients

Investigating young atypical stroke risk factors and etiologies in Native Hawaiian and pacific islander populations

Investigating young atypical stroke risk factors and etiologies in Native Hawaiian and pacific islander populations

Applying the World Stroke Organization roadmap in planning a model for stroke service implementation in Matrouh Governorate-Egypt: a World Stroke Organization young future stroke leaders’ analytical study

BackgroundThe global incidence of stroke is on the rise, primarily due to an increase in the aging population and the prevalence of vascular risk factors among the elderly. However, stroke is a treatable condition if promptly recognized and managed effectively. To optimize stroke management, it is crucial to establish a well-prepared infrastructure comprising adequately trained physicians working in collaboration with multidisciplinary teams. Equipped stroke units, easily accessible emergency medical services with a stroke code, and interconnected telestroke networks, further enhance stroke care delivery. Along with the current study, conducted by a task force from the World Stroke Organization’s Future Stroke Leaders Program, an assessment of the stroke infrastructure within Matrouh governorate in Egypt for stepwise implementation of stroke services, based on the World Stroke Organization’s stroke roadmap took place. The study consisted of two levels: Level One involved analyzing existing gaps that may impede the implementation of stroke services, while Level Two proposed strategies to address these gaps using a problem-solving approach.ResultsThe study identified the Matrouh governorate as a suitable region for stroke service implementation. The region exhibits a blend of urban and rural areas and is geographically distant from major healthcare centers. Matrouh also possesses a diverse population, subject to seasonal variations. Currently, it offers a mix of minimum and essential stroke services, which can be expanded and improved through a step-by-step approach guided by the World Stroke Organization’s stroke roadmap.ConclusionsMapping stroke infrastructures allows for the identification of potential gaps to optimize the potential for implementation of stroke services.

Anatomical features of PFO in patients with cryptogenic stroke in comparison to autopsy results

Abstract Background In young patients suffering a stroke, well over 30% is considered cryptogenic stroke and may be associated with a PFO. The anatomical characteristics of stroke-related PFOs that allow right-to-left shunting can be assessed with TEE. The prevalence of a PFO in autopsy studies is approximately 25%, suggesting that the a priori chance of finding a possible "bystander-PFO" in young stroke victims is substantial. Purpose To assess the anatomical characteristics of PFO in patients with cryptogenic stroke and compare these with previously published results from autopsy in the general population. Methods Data on all consecutive patients that underwent PFO closure from 2016 to 2022 were collected. Anatomical PFO characteristics, including PFO diameter, tunnel length and the presence of atrial septal aneurysm, were measured with TEE during the closure procedure and analyzed by two cardiologists. Results In total 228 patients were enrolled. The mean age was 43±11 years, 116 patients (50.9%) were male, the mean RoPE-score was 7.0±1.4. The most frequent shunt grade measured with contrast bubble study during Valsalva maneuver was 3 (&amp;gt;25 bubbles, without opacification). Patients were divided in two groups depending on how the PFO diameter was measured, unstretched (n=119) and stretched (n=109). The mean PFO diameter was 5.4±2.6mm in the unstretched group and 10.9±3.6mm in the stretched group compared to 4.9±2.6mm in previous autopsy (p=0.192 and p&amp;lt;0.001, respectively). The percentage of patients with a PFO size larger than 10mm was 2% in autopsy compared to 6% in the unstretched group (p=0.109) and 52% in the stretched group (p&amp;lt;0.001). The mean PFO tunnel length in our combined cohort was 7.8±2.9mm. Conclusion The difference in PFO diameter found in this study indicates that PFOs found during published autopsy series, which are present in approximately 25% of the population, are significantly smaller than those related to a cryptogenic stroke. The exact prevalence of PFOs in the population that are comparable to those in cryptogenic stroke patients remains thus unknown. Future studies should define which characteristics could classify or rule out a PFO prone for associated clinical conditions, such as cryptogenic stroke.Distribution of PFO size

Abstract 260: TCD Bubble test as a Screening tool for detection of Patent Foramen Ovale in Stroke

Introduction Introduction &amp; Objectives: Transcranial Doppler (TCD) ultrasound provides rapid, noninvasive, real‐time measures of cerebrovascular function. Patent Foramen Ovale (PFO) is fourfold more common in Young Stroke Patients &lt;55 years of age, as opposed to age‐matched controls. The PFO test with TCD, often called a “TCD bubble test,” involves the intravenous injection of micro‐bubbles (air mixed with saline), which can be detected by a TCD system in the Middle Cerebral artery (MCA). The TCD Bubble test, hence, can be used as a screening test in the evaluation of Embolic Stroke Of Undetermined Source. Methods A retrospective observational study was carried out at Aster MIMS Hospital, Kozhikode, where 63 patients with Young stroke were evaluated between April 2021 and October 2022. Along with routine stroke workup, including Transthoracic Echocardiography, TCD bubble tests were performed to detect Right to left shunt. Further, Transesophageal Echocardiography was done to look for Patent Foramen Ovale in TCD Bubble test positive patients. Results TCD Bubble test was detected to be positive in 36 patients and negative in 27 patients. Transesophageal Echocardiography performed in TCD Positive patients confirmed PFO in 35 out of 36 patients. Transthoracic echocardiography, however, could detect PFO only in 10 patients. Conclusion TCD Bubble test can be employed as a screening tool in the evaluation of young stroke to detect Patent Foramen Ovale with efficacy similar to TEE.

Obesity-hyperlipidemia, Hypertension, and Left Atrial Enlargement During Stroke in Young Adults.

This study investigated the association between left atrial enlargement and stroke severity in young adults. We also studied the differences between the normal and left atrial enlargement groups in clinical data. A total of 135 young stroke patients admitted to the Department of Neurology of the Taizhou People's Hospital were recruited from January 2018 to December 2021. The patients were divided into normal and enlarged groups by left atrial size. The relationship between the left atrial diameter and the National Institutes of Health Stroke Scale score was analyzed apart from the differences in clinical variables. No relationship was observed between the left atrial diameter and the National Institutes of Health Stroke Scale score (r=-0.045 P=0.603). The univariate analysis of both groups revealed that hypertension (P=0.004), hyperlipidemia (P=0.001), body mass index (P=0.000), obesity (P=0.015), and not stroke etiologic subtypes were associated with left atrial enlargement. In binary logistic regression analysis models, hyperlipidemia 3.384 (95% CI, 1.536 to 7.452), hypertension 2.661 (95% CI, 1.066 to 6.639), and obesity 2.858 (95% CI, 1.158 to 7.052) were significantly associated with the young stroke of left atrial enlargement. In young adults, obesity-hyperlipidemia and hypertension were significantly associated with left atrial enlargement in stroke.

4 The Association Between Pro-Inflammatory Cytokines and C-Reactive Protein and the Cognitive and Neurological Outcome in Stroke Survivors: A Systematic Review

Objective:Childhood ischemic and hemorrhagic stroke is often associated with neuropsychological and cognitive deficits. Stroke induces an inflammatory response in the central and peripheral nervous systems. High levels of inflammatory markers in the plasma have been associated with poorer cognitive outcomes. The role of inflammation in neurological prognosis of stroke has been studied previously; however, there is a limited understanding of the association between inflammatory markers and neuropsychological outcome post-stroke. The present review examined the existing literature on the association between inflammatory markers and post-stroke functioning.Participants and Methods:Data bases (PsycINFO, PubMed, Web of Science, and Ovid) were reviewed in October 2020. Articles were restricted to English-language literature. Articles were included regardless of recruitment setting, number of strokes, mechanism of stroke, timing of blood collection and outcome assessment. The articles focused on patients with stroke (between the ages of 0 to 95), measured post-stroke outcome by neurological and cognitive outcome measures (i.e., it included findings on any aspect of cognition such as memory, information processing, or attention), and on pro-inflammatory cytokines and c-reactive proteins as measures of inflammation. The systematic literature search retrieved 954 articles to review against inclusion criteria. Descriptive statistics were performed using IBM SPSS 27.0 Statistics Software.Results:A total of 18 articles were included in this review. The population age ranged from 21 to 95, and, when reported (n=17), mean participant age was 66.31. Among stroke patient populations, ischemic stroke was most researched (n=15). The most widely investigated biomarkers were CRP (n=9), IL-6 (n=8), TNF- a (n=7), IL-1 b (n=5), and IL-10 (n=5). The time of initial blood collection ranged from on admission to within 3 months poststroke. Equal number of studies used both neurological and cognitive tests (n=7), or only neurological (n=7), 2 studies only used cognitive tests, and one study used all three types of measures. The most commonly used cognitive test was the Mini Mental State Examination, MMSE (n=7). The next commonly used cognitive test was the Montreal Cognitive Assessment (MoCA), (n=4). Only two studies used a comprehensive neuropsychological battery.Conclusions:There is a lack of research into diverse stroke populations. All the studies examined the association between inflammatory markers and the post-stroke outcomes in adult populations and mostly in patients with ischemic stroke. The lack of research on pediatric and young adult stroke represents a significant gap in understanding predictors of neurological and cognitive outcomes. Further, the review revealed a lack of comprehensive neurocognitive assessment post stroke, with most studies measuring neuropsychological outcome using brief cognitive instruments. Our findings highlight a critical need for addressing the above gaps to help elucidate the role of inflammatory markers in the neuropsychological prognosis of stroke in younger populations.

Depressive Symptoms in Young and Middle-Aged Stroke Patients: A Transition Analysis.

There is heterogeneity in depressive symptoms. However, latent classes of depressive symptoms and the transition and influences of these in young and middle-aged stroke patients are unclear. The aim of this study was to identify the latent classes of depressive symptoms and their transition patterns over time and the influencing factors in young and middle-aged stroke patients from stabilization to 6 months after discharge. This is a longitudinal study following the Strengthening the Reporting of Observational Studies in Epidemiology checklist. A total of 272 young and middle-aged stroke participants were recruited from a hospital neurology ward in Henan Province, China. Participants completed a questionnaire on sociodemographic and health information. Latent transition analysis was used to evaluate the transition pattern of latent classes from stabilization to 6 months after discharge and its influencing factors. One hundred seventy-nine participants were included in the analysis. Three latent classes of depressive symptoms were identified as "mild symptoms," "grief-sleep-fatigue symptoms," and "severe symptoms." Most participants remained in the original latent class from stabilization to 6 months after discharge (probability of 83.8%, 83.8%, and 88.8%). From 3 to 6 months after discharge, the participants with fewer complications were more likely to transition into the mild symptom class. The findings indicate that from stabilization to 6 months after discharge, depressive symptoms in young and middle-aged stroke patients in China transitioned gradually from the severe symptom class to the mild symptom. Patients with fewer numbers of poststroke complications were more likely to transition to the mild symptoms class. Future research should focus on depressive symptoms in early-stage stroke patients and provide sufficient psychological support to patients with a high number of complications.

Stroke of Misfortune: Unpacking the Association between Cannabis and Young Stroke

Stroke of Misfortune: Unpacking the Association between Cannabis and Young Stroke

Thirty-day mortality rates among young adult stroke patients and their characteristics at Kiruddu and Mulago hospitals in Uganda: A prospective observational cohort study.

Stroke outcomes among young adults in Uganda are unclear. This study therefore determined the clinical characteristics and 30-day outcome among young adults with an acute stroke. In a prospective observational cohort study, 61 young adults with confirmed stroke were followed up for 30 days. Socio-demographic and clinical characteristics were collected using a study questionnaire. Kaplan-Meier curves, and modified Poisson regression were performed for factors associated with the 30-day mortality outcome. A third of the screened stroke survivors, (61/195) were young adults aged between 18 and 50 years. About two-thirds were male. More than half were diagnosed with ischaemic strokes while 42.6% had a haemorrhagic stroke. Nearly half (29/61) were known hypertensives, 43% (26/61) had a history of alcohol consumption with 95% classified as dependent on CAGE assessment. Ten percent had a prior smoking history while 29% of the female gender had a prior history of oral contraception use. Twenty-three percent (14/61) of the young stroke patients died within 30 days of stroke onset (95% CI: 0.01, 0. 901). A history of smoking (adjusted prevalence ratio: aPR;5. 094, 95% CI: 3.712, 6. 990) and stroke severity National Institutes of Health Stroke score (NIHSS) >16; Prevalence ratio (PR) -3. 301, 95%CI: 1. 395, 7. 808) and not drinking alcohol (aPR (adjusted prevalence ratio) -7. 247, 95% CI: 4. 491, 11.696) were associated with 30- day mortality. A third of all stroke survivors were young adults. About 23. 3% died within 30 days of stroke onset. Stroke severity and a history of smoking were associated with mortality. Identifying high risk patients and early outpatient follow up may help reduce the 30-day mortality in our settings.

Functional brain connectivity in young adults with post-stroke epilepsy.

Approximately 1 in 10 young stroke patients (18-50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke epilepsy and their relationship with cognitive impairment. Therefore, we aimed to investigate whether young ischaemic stroke patients have altered functional networks and whether this alteration is related to cognitive impairment. We included 164 participants with a first-ever cerebral infarction at young age (18-50 years), along with 77 age- and sex-matched controls, from the Follow-Up of Transient Ischemic Attack and Stroke patients and Unelucidated Risk Factor Evaluation study. All participants underwent neuropsychological testing and resting-state functional MRI to generate functional connectivity networks. At follow-up (10.5 years after the index event), 23 participants developed post-stroke epilepsy. Graph theoretical analysis revealed functional network reorganization in participants with post-stroke epilepsy, in whom a weaker (i.e. network strength), less-integrated (i.e. global efficiency) and less-segregated (i.e. clustering coefficient and local efficiency) functional network was observed compared with the participants without post-stroke epilepsy group and the controls (P < 0.05). Regional analysis showed a trend towards decreased clustering coefficient, local efficiency and nodal efficiency in contralesional brain regions, including the caudal anterior cingulate cortex, posterior cingulate cortex, precuneus, superior frontal gyrus and insula in participants with post-stroke epilepsy compared with those without post-stroke epilepsy. Furthermore, participants with post-stroke epilepsy more often had impairment in the processing speed domain than the group without post-stroke epilepsy, in whom the network properties of the precuneus were positively associated with processing speed performance. Our findings suggest that post-stroke epilepsy is associated with functional reorganization of the brain network after stroke that is characterized by a weaker, less-integrated and less-segregated brain network in young ischaemic stroke patients compared with patients without post-stroke epilepsy. The contralesional brain regions, which are mostly considered as hub regions, might be particularly involved in the altered functional network and may contribute to cognitive impairment in post-stroke epilepsy patients. Overall, our findings provide additional evidence for a potential role of disrupted functional network as underlying pathophysiological mechanism for cognitive impairment in patients with post-stroke epilepsy.

Risk factors for stroke recurrence in young patients with first-ever ischemic stroke: A meta-analysis.

At present, the incidence rate of ischemic stroke in young people is increasing yearly, and the age of onset is increasingly young. Therefore, primary and secondary prevention of ischemic stroke in young people, especially secondary prevention, is particularly crucial. We aimed to comprehensively evaluate risk factors for stroke recurrence in first-ever young ischemic stroke (YIS) patients. The meta-analysis was used to quantitatively analyze the research results on risk factors for stroke recurrence in first-ever YIS patients both domestically and internationally. Stata12.0 software was used for heterogeneity testing, publication bias analysis, sensitivity analysis, and the calculation of combined odds ratios and 95% confidence intervals. The odds ratio (OR) values of the relationship between hypertension and hyperlipidemia and recurrence of first-ever YIS were 1.54 (1.05-2.26) and 1.12 (1.00-1.25), respectively. The OR values of male sex, type 2 diabetes, smoking, drinking and YIS recurrence were 1.66 (0.98-2.79), 1.01 (0.64-1.59), 1.21 (0.83-1.76), and 1.28 (0.82-2.53), respectively. The relationship between male sex, type 2 diabetes, smoking, drinking and YIS recurrence was ambiguous. Hypertension and hyperlipidemia are important risk factors for stroke recurrence in first-ever YIS patients, and active intervention should be taken.

Ischemic and hemorrhagic strokes in young adults: Comparison of functional outcomes and return to work after stroke

BackgroundFunctional recovery and return to work (RTW) after stroke are important rehabilitation goals that have significant impact on quality of life. Comparisons of functional outcomes and RTW between ischemic stroke (IS) and hemorrhagic stroke (HS), especially among young adults with stroke, have either been limited or yielded inconsistent results. We aimed to assess functional outcomes and ability to RTW in young adults with IS and HS, specifically primary spontaneous intracranial hemorrhage (SICH). MethodsYoung adults with IS or SICH aged 18–50-years-old were included. Outcome measures were modified Rankins score (mRS) on discharge and 3-months and RTW at 3-months after stroke. Good functional outcome was defined as an mRS of 0–2. ResultsWe included 459 patients (71.5% male) with a mean age of 43.3 ± 5.7 years, comprising 49.2% IS and 50.8% SICH. Patients with SICH were more likely to have unfavourable shifts in ordinal mRS on discharge (OR 7.52, CI 5.18–10.87, p < 0.001) and at 3-months (OR 6.41, CI 4.17–9.80, p < 0.001). Patients with IS more likely achieved good functional outcomes (80.2% vs. 51.8%, p < 0.001) and were able to RTW at 3-months (54.4% vs. 36.3%, p = 0.004). Among all stroke patients with good functional outcomes, one-third did not RTW at 3-months. Patients with longer length of hospitalisation and higher National Institutes of Health Stroke Scale (NIHSS) score on admission, especially in the domain categories of level of consciousness, vision, motor function, language and neglect, were less likely to RTW at 3-months. ConclusionPatients with IS were more likely to RTW when compared to SICH patients. Many young stroke patients did not RTW despite good functional outcomes. Further research should therefore address differences in prognosis and identify predictors that influence ability to RTW after stroke in the young adult population.

Activation of cerebral Ras-related C3 botulinum toxin substrate (Rac) 1 promotes post-ischemic stroke functional recovery in aged mice.

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged (male, 18 to 22 months old C57BL/6J) brain after ischemic stroke. We found that as mice aged, Rac1 expression declined in the brain. Delayed overexpression of Rac1, using lentivirus encoding Rac1 injected day 1 after ischemic stroke, promoted cognitive (assessed using novel object recognition test) and sensorimotor (assessed using adhesive removal tests) recovery on days 14-28. This was accompanied by the increase of neurite and proliferative endothelial cells in the peri-infarct zone assessed by immunostaining. In a reverse approach, pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells. Furthermore, Rac1 inhibition reduced the activation of p21-activated kinase 1, the protein level of brain-derived neurotrophic factor, and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke. Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

Piloting Res-ET: A Remote Inspiratory Muscle Strength Training Intervention On Young Stroke Survivors

Piloting Res-ET: A Remote Inspiratory Muscle Strength Training Intervention On Young Stroke Survivors