Stroke, Volume 56, Issue Suppl_1, Page A82-A82, February 1, 2025. Background:Spontaneous intracerebral hemorrhage (sICH) is a neurological condition characterized by the rupture of blood vessels within the brain, resulting in the formation of a hematoma and subsequent brain injury. Tobacco use is a major modifiable risk factor for sICH and is associated with worsened outcomes following the occurrence of sICH. Tobacco use is also correlated with worsened outcomes following sICH. Previously, we observed that prior chronic exposure to nicotine results in increased hematoma volume following collagenase-induced sICH when compared to saline-exposed animals. This study aims to evaluate the effect of prior chronic nicotine exposure on long-term outcomes post-sICH.Hypothesis:Prior chronic nicotine exposure will result in more significant brain damage following an autologous blood injection-induced sICH.Methods:Young male and female (estrous matched) rats were randomly assigned to a saline (control) or nicotine-exposed group. Rats received nicotine or saline via. osmotic pumps for 2-3 weeks. The pump was removed before the induction of sICH by the stereotaxic injection of autologous blood into the striatum. The autologous blood injection-induced sICH model was used to obtain equal hematoma volume in all experimental groups. Rats then underwent perfusion fixation, and brains were harvested for histopathological analysis. Paraffin-embedded brain blocks were cut into 10 µm coronal sections between bregma -2.0 to +2.0, stained with hematoxylin and eosin, scanned with a high-resolution scanner, and analyzed using ImageJ to measure lesion area. Student’s t-test was used to determine significant differences in mean lesion volume between treatment groups. Two-way ANOVA was used to assess the interaction effect between sex and lesion volume.Results:For the male group, the brain lesion volume in nicotine-exposed rats was significantly (p
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Abstract TP323: Increased Correlation between Hypertensive and Hypertensive Renal Disease Mortality and Stroke Death: Health Disparity Affecting the U.S. Non-Hispanic Population during the COVID-19 Pandemic
Stroke, Volume 56, Issue Suppl_1, Page ATP323-ATP323, February 1, 2025. Introduction:Hypertension is one of the leading causes of mortality. The direction and strength of the association between death from hypertensive and hypertensive renal disease and stroke mortality during the COVID-19 pandemic among different U.S. ethnic groups is unclear.Hypothesis:Hypertensive and hypertensive renal disease mortality is positively correlated with increased stroke death overtime during the COVID-19 pandemic. We aim to examine the correlation between mortality from Hypertensive and hypertensive renal disease and stroke before and after the COVID-19 pandemic among U.S. Hispanic and non-Hispanic populations.Methods:A database query from the U.S. Centers Disease for Control and Prevention (CDC) Wonder was retrieved. A yearly age-adjusted mortality from hypertension or hypertensive renal disease from 2017 to 2022 was correlated with the mortality from stroke by Pearson’s correlation coefficient. Further analyses were performed by stratified data before and after 2019 as well as among Hispanic and non-Hispanic subgroups.Results:Age-adjusted mortality from hypertension and hypertensive renal disease trended down before the COVID-19 pandemic (from 9 to 8.91 deaths per 100,000 populations) but trended up after the pandemic (from 10.08 to 10.29 deaths per 100,000 populations). A similar trend occurred in age-adjusted mortality from stroke (from 37.59 to 36.59 deaths per 100,000 populations during pre-pandemic and from 38.84 to 39.53 deaths per 100,000 populations during post-pandemic). Those overall cause-specific mortalities are highly correlated with the correlation coefficient of 0.9697 (Figure 1). The correlation remained but slightly attenuated among Hispanics, while more pronounced among non-Hispanics (0.9649 and 0.9680, respectively; Figures 2 and 3). Stratified by time-related to the COVID-19 pandemic, age-adjusted mortality from hypertension and hypertensive renal disease and stroke trended down before the COVID-19 pandemic but trended up after the pandemic. The correlation was 0.9866 before the pandemic and up to 0.9988 during the pandemic (Figures 1, 2, and 3).Conclusions:Hypertensive and hypertensive renal disease mortality as well as stroke mortality have trended up and increased during the COVID-19 pandemic, particularly among the non-Hispanic population. Further investigations are required to mitigate health and ethnic disparities, especially during high demand for limited resources.
Abstract TP337: Blocking insulin-like growth factor 1 receptor in the gut abrogates IGF-1 mediated long-term neuroprotection in middle-aged female rats
Stroke, Volume 56, Issue Suppl_1, Page ATP337-ATP337, February 1, 2025. Background and Purpose:Our previous studies in a rat model of ischemic stroke identified that intraperitoneal (IP), but not intracerebroventricular (ICV) administration of IGF-1 reduced stroke-induced gut leakiness and peripheral inflammation in the acute phase and attenuated stroke-induced impairment in acyclic middle-aged female rats. These data suggest that the gut may be implicated in IGF-1-mediated effects on stroke-induced cognitive impairment. To directly assess whether the effect of IGF-1 on behavioral improvement is mediated by the gut, study utilized a novel tet-inducible rAAV construct to block IGF1R specifically in the gut.Methods:Female Sprague Dawley rats (9-11 mo) were intragastrically gavaged with either recombinant rAAV construct containing IGFR-shRNA (IGFR-sh) downstream of the IESC promoter Lgr5 in a Tet-inducible system or rAAV-empty vector (Scr-sh) 4 weeks prior to experimental ischemia. Animals were subjected to endothelin-1 induced MCAo. Doxycycline was administered 4h later and IGF-1 was given ip at 4 and 24 h post-stroke. Sensorimotor function as well as peripheral inflammation (in serum samples) was assessed at 5d post-stroke and long-term cognitive impairment was evaluated after 60 days.Results:The mCherry reporter in the rAAV construct was observed in the intestinal crypt, indicating appropriate delivery of the construct. Sensorimotor function evaluated by vibrissae evoked forelimb placement task was significantly impaired in the ipsilateral paw after stroke in IGFR-Sh+IGF-1 compared to Scr-sh+IGF-1(p
Abstract TP122: Impact of 2021 Seconary Stroke Prevention Guidelines on Post Stroke Care Plans for Patients Transferred to Long Term Acute Care Facilities
Stroke, Volume 56, Issue Suppl_1, Page ATP122-ATP122, February 1, 2025. Background:Classification of etiologic ischemic stroke subtype guides post-stroke care and secondary prevention. Etiologic ischemic stroke subtypes are often not clearly documented in post-stroke care plans especially when transferring from one facility to another. In 2021, AHA/ASA published updated secondary stroke prevention guidelines recommending identifying etiologic ischemic stroke subtypes when possible. The impact of this on post-stroke care is unknown.Methods:Charts of all patients ages 18 and up, admitted from 1/1/20 to 5/23/21 and from 1/1/22 to 5/23/23 to 3 long-term acute care (LTAC) facilities, on antiplatelet therapy, and with an ascertainable history of stroke within 90 days of admission, were retrospectively reviewed to assess for documentation of ischemic stroke subtype at discharge/transfer to an LTAC facility and to assess for appropriateness of secondary stroke prevention therapies. Care plans from those two time periods were compared to assess for any impact the 2021 guidelines may have had on discharge practices.Results:Subtypes were not defined for the majority of ischemic strokes. Classification by etiologic subtype was observed in 33% of cases. Classification by territory or location was more common (Fig. 1). One-quarter of patients were on dual antiplatelet therapy (DAPT) and 75% of patients were on single antiplatelet therapy (SAPT) with more patients on DAPT in the latter time period (Fig. 2A). Rationale for DAPT were not provided for the majority of patients and NIHSS and ABCD2 scored were also not commonly provided for patients on DAPT (Fig. 2B). Close to 90% of patients were treated with antihypertensives and statin therapy at discharge to LTAC; 71% of patients were treated with diabetic therapies at discharge; stroke education at discharge to LTAC was documented for 43% of patients; and LDL was documented in 56% of patients (Fig. 3).Conclusions:Etiologic ischemic stroke subtypes were not documented for the majority of patients transferred to LTACs. Despite recent guideline revisions, an increase in documentation of stroke subtype was not observed. Optimal secondary stroke prevention strategies were difficult to assess without this information including appropriate antiplatelet regimens. Our findings highlight the importance of the need to improve post-stroke care plans at discharge and transfer including documentation of etiologic ischemic stroke subtypes to facilitate optimal post-stroke care across all transitions.
Abstract TP369: Alpha7 nicotinic acetylcholine receptor plays a beneficial role in long-term cognitive recovery after stroke.
Stroke, Volume 56, Issue Suppl_1, Page ATP369-ATP369, February 1, 2025. Introduction:The cholinergic anti-inflammatory pathway regulates immune responses through the alpha7 nicotinic acetylcholine receptor (α7nAChR), found in neurons, macrophages, and monocytes. α7nAChR activation via agonists or Vagus nerve stimulation (VNS) reduces pro-inflammatory cytokines in disease models. In young mice, pharmacological activation or stimulation of the Vagus nerve has been shown to mitigate ischemic stroke injury by reducing brain and peripheral inflammation and oxidative stress. However, the role of α7nAChR in long-term stroke outcomes remains unclear.Methods:Young (8-12 weeks) male wild-type (WT) and α7nAChR knockout (KO) mice underwent middle cerebral artery occlusion (MCAO) for 60 minutes. After 24 hours, brain acetylcholine levels and α7nAChR expression were assessed by mass spectrometry and western blot respectively. Microglia, macrophage counts, and TNF-α expression were evaluated using flow cytometry. Long-term behavioral tests included the Barnes maze (days 7 and 30), novel object recognition (day 10), and object location tests on day 20. A second cohort was euthanized on day 7 for brain-infiltrated immune cell analysis.Results:At 24 hours post-MCAO, brain α7nAChR expression decreased significantly without changes in acetylcholine levels. WT MCAO mice showed reduced microglia, increased microglial TNF-α expression, and fewer α7nAChR-positive microglia compared to shams (p
Abstract 16: Short and long term efficacy of Colchicine for prevention of stroke and major adverse cardiovascular events: A Meta-analysis with CHANCE 3, and CONVINCE randomized controlled trials.
Stroke, Volume 56, Issue Suppl_1, Page A16-A16, February 1, 2025. Background:Colchicine has shown to reduce major adverse cardiovascular events and stroke among patients with coronary artery disease. However, its efficacy with short and long use and risk of stroke has not been well studied with conflicting results till date.Objective:We sought to evaluate the short and long term efficacy of Colchicine for prevention of stroke and major adverse cardiovascular events (MACE).Methods:We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (OR) were pooled using a random-effect model, and a p-value of
Abstract 37: Long-Term Results of Bypass Surgery for Symptomatic Carotid and Middle Cerebral Artery Occlusion (CMOSS-FU)
Stroke, Volume 56, Issue Suppl_1, Page A37-A37, February 1, 2025. Background:In the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS), we found no significant difference between the bypass surgery group and the medical group with respect to the primary composite outcome of stroke or death within 30 days or any subsequent ipsilateral ischemic stroke within 2 years of follow-up. We now extend the long-term follow-ups to 10 years.Methods:We randomly assigned symptomatic patients with hemodynamically compromised internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion to extracranial-intracranial (EC-IC) bypass surgery plus medical treatment or medical treatment alone at 13 centers in China. We extended the follow-ups from the original 2 years to 10 years to assess long-term outcomes. The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days after randomization.Results:324 patients were assigned to the surgery (n=161) or medical group (n=163); the median duration of follow-up was 7.6 years (interquartile range [IQR], 2.3 to 9.2). The primary outcome occurred in 18 of 161 patients (11.2%) in the surgical group, significantly lower than that in the medical group (32 out of 163 patients [19.6%]; relative risk [RR], 0.57; 95% confidence interval [CI], 0.33 to 0.97; P=0.04). The risk of any stroke was 16.1% in the surgical group vs 23.3% in the medical group (RR, 0.76; 95% CI, 0.52 to1.13; P=0.15); the all-cause mortality was 8.1% in the surgical group vs. 8.6% in the medical group (RR, 0.94; 95% CI, 0.46 to 1.94]; P=0.93).Conclusions:Among symptomatic ICA or MCA occlusion patients with hemodynamic insufficiency, the addition of extracranial-intracranial bypass surgery to medical treatment was safe and led to a lower risk of recurrent stroke through 7 years of follow-up than medical treatment alone. (ClinicalTrials.gov number, NCT01758614.)
Abstract WP43: Factors related to major recanalization after second coiling for recanalized aneurysms: a multicenter experience over 20 years during long-term follow-up
Stroke, Volume 56, Issue Suppl_1, Page AWP43-AWP43, February 1, 2025. Objective:Recanalized aneurysms may still recanalize despite a second coiling to prevent rupture. Factors related to recanalization following a second coiling for recanalized aneurysms have not yet been fully explored. This study examined a large multicenter dataset accumulated over a 20-year period to identify factors related to major recanalization following a second coiling for recanalized aneurysms.Methods:A total of 185 patients with 188 aneurysms who underwent second coiling for saccular unruptured cerebral aneurysms at three institutions between November 2003 and December 2023 were retrospectively reviewed. Patients were categorized into a group with major recanalization (R group) and a group without major recanalization (NR group). To identify factors related to major recanalization, clinical, anatomic, and procedural factors were comparable between groups by multivariate logistic regression analysis and stepwise selection.Results:During the follow-up period (mean, 62.3 ± 51.2 months), 72 (38.3%) of 188 recanalized aneurysms developed major recanalization. Compared with the NR group, the R group had significantly larger aneurysm size, neck size, and aneurysm volume at initial coiling and significantly lower rates of stent-assisted coiling, use of an intermediate catheter, and complete occlusion at second coiling. Stepwise multivariate logistic regression analysis identified neck size at initial coiling (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.03–1.32) as an independent risk factor for major recanalization and stent-assisted coiling (OR 0.34; 95%CI 0.14–0.85), use of an intermediate catheter (OR 0.38; 95%CI 0.17–0.86), and complete occlusion at second coiling (OR 0.16; 95%CI 0.034–0.72) as independent protective factors for major recanalization.Conclusions:Second coiling of recanalized aneurysms may decrease the risk of major recanalization by using a stent in combination with an intermediate catheter to achieve complete occlusion.
Abstract WP39: Pretreatment Factors Associated with Symptomatic Stroke in Moyamoya Disease Patients: Long-Term Multicenter Experience
Stroke, Volume 56, Issue Suppl_1, Page AWP39-AWP39, February 1, 2025. Background:Moyamoya disease (MMD) is a cerebrovascular disorder marked by the progressive steno-occlusion of the bilateral internal carotid arteries and the formation of abnormal collateral vessel networks at the base of the brain. Previous studies have attempted to identify risk factors predictive of postoperative complications to improve patient management. This study aims to identify pretreatment factors associated with symptomatic stroke in MMD patients.Methods:This study is a multicenter retrospective analysis conducted across 13 academic institutions in North America. A total of 518 patients with MMD were included. Data collected included patient demographics, disease characteristics, and follow-up duration. Stroke-free survival was analyzed using Kaplan-Meier curves. Univariate and multivariable Cox regression analyses were used to identify risk factors for symptomatic stroke.Results:The median age of the patients was 43 years (IQR, 34–52 years), and 370 (71%) were females. Hypertension was present in 255 (49%) patients, diabetes mellitus in 144 (28%), and 192 (37%) were smokers. Multivariable Cox regression identified advanced age (HR 1.03, 95% CI 1.01–1.05, p = 0.011), female sex (HR 2.03, 95% CI 1.00–4.11, p = 0.049), diabetes mellitus (HR 2.03, 95% CI 1.14–3.63, p = 0.016), smoking status (HR 2.27, 95% CI 1.27–4.05, p = 0.006), and incidental findings (HR 0.37, 95% CI 0.15–0.93, p = 0.034) as significant factors associated with symptomatic stroke.Conclusion:Advanced age, female sex, diabetes mellitus, and smoking status were significant predictors of symptomatic stroke in MMD patients. Patients with incidental findings had a reduced risk of stroke. These findings emphasize the importance of managing modifiable risk factors and the potential benefits of early detection in improving clinical outcomes for MMD patients. Further prospective studies are needed to validate these findings.
Abstract WP309: Long-Term Efficacy And Safety Of Patent Foramen Ovale Closure In Elderly Patients Over 60 Years With Cryptogenic Stroke: A Systematic Review And Meta-Analysis
Stroke, Volume 56, Issue Suppl_1, Page AWP309-AWP309, February 1, 2025. Background:Patent foramen ovale (PFO) is commonly diagnosed in patients over 60-65 years with cryptogenic stroke. Despite robust evidence and guidelines supporting PFO closure in individuals aged 18-60, the efficacy of this intervention in preventing recurrent ischemic strokes in elderly patients ( >60 years) with PFO and cryptogenic stroke remains uncertain, as existing evidence is inconclusive.Objective:We aimed to synthesize findings from observational studies until July 2024 to evaluate the long-term efficacy and safety of PFO closure in elderly patients over 60 years of age, with the primary outcome focused on its impact on reducing the composite risk of recurrent ischemic stroke/transient ischemic attack (TIA).Methods:We analyzed data using RevMan 5.4 with a random effects model, employing the inverse variance method pooling outcomes as odds ratios (OR) with 95% confidence intervals (CI). Our study protocol is registered in PROSPERO (CRD42024564171).Results:Our study included 9 observational studies comprising 3,525 subjects, of whom 1,572 were elderly patients aged over 60 years. The average follow-up period ranged from 2.5 to 14 years. Upon pooled analysis comparing the primary composite outcome of recurrent ischemic stroke/TIA after PFO closure, the elderly cohort (aged >60 years) demonstrated a significant reduction in risk compared to the non-elderly (18-60 years), with an OR of 3.47 (95% CI: 2.01 to 5.99, p < 0.00001), and no significant heterogeneity was observed. Secondary outcomes revealed a statistically significant reduction in all-cause mortality among the elderly following PFO closure (OR: 7.83, 95% CI: 2.59 to 23.65, p = 0.0003), as well as a decreased incidence of recurrent strokes (OR: 3.97, 95% CI: 1.58 to 9.97, p = 0.003). Furthermore, there was no statistically significant difference in the occurrence of post-procedure new-onset atrial fibrillation between elderly and younger patients (OR: 1.31, 95% CI: 0.67 to 2.57, p = 0.43).Conclusion:PFO closure in elderly patients may be as effective and safe as in younger patients. However, there is a pressing need for further multicenter large randomized controlled trials to specifically include patients over 60 years of age. These trials should evaluate the safety and long-term efficacy of PFO closure, with the goal of reassessing and refining current treatment guidelines to optimize outcomes for elderly patients with PFO and cryptogenic stroke.
Abstract 162: Imbalanced VWF–ADAMTS13 axis mediates the detrimental impact of preceding bacterial or COVID-19 respiratory tract infections on stroke
Stroke, Volume 56, Issue Suppl_1, Page A162-A162, February 1, 2025. Background:Preceding respiratory tract infections (RTIs) caused by bacteria or viruses are associated with worse stroke outcomes, likely due to an exaggerated inflammatory immune response, endothelial dysfunction, platelet activation, and coagulopathy. Recent studies have revealed increased plasma von Willebrand factor (VWF) levels and reduced ADAMTS13 activity (the risk factors for stroke) in patients with RTIs, including COVID-19. However, it remains unclear whether an imbalance in the VWF–ADAMTS13 axis plays a causative role in the pathophysiology ofS. aureus- or COVID-19-associated stroke severity or is merely an associative marker of disease status.Objective:To examine whether an imbalance in the VWF–ADAMTS13 axis is a causal link between RTIs and stroke severity.Methods:Wild-type (WT) mice (3–4 months old) were infected intranasally with sublethal doses ofS. aureus(on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0). On day 6 (S. aureus) or day 3 (SARS-CoV-2), the infection was confirmed to be localized in the lungs (but not in the brain) and the plasma VWF levels and ADTMTS13 activity were quantified. In another set of experiments, WT,Vwf−/−, andAdamts13−/−mice (3–4 months old) with respective littermate controls were subjected to transient (30 or 45 min) cerebral ischemia (filament stroke model) followed by reperfusion. For theS. aureusexperiments, brain infarcts were assessed on day 2 post-reperfusion and functional outcomes (corner test, wire hanging test, modified neurological severity score, and rotarod test) on week 1 and 4 post-reperfusion. For the SARS-CoV-2 experiments, brain infarcts and functional outcomes (the Bederson score) were assessed on day 1 post-reperfusion.Result:We demonstrated thatS. aureusor SARS-CoV-2 infection localized to the lungs in the WT mice resulted in increased (2–3 fold) plasma VWF levels and reduced ADAMTS13 activity, concomitant with larger infarcts and worse functional outcomes (P
Abstract WP355: Long wavelength light exposure reduces ischemic stroke brain injury through reduced platelet function
Stroke, Volume 56, Issue Suppl_1, Page AWP355-AWP355, February 1, 2025. Introduction:Variations in light exposure are associated with changes in inflammation. The risk of thrombotic events such as ischemic stroke have been found to oscillate with the day-light cycle.Aim:To investigate the impact of altering the light spectrum on ischemic stroke brain injury.Methods:Mice were exposed to ambient (mice-white, 300lux), red light (mice-red, 617nm) or blue light (mice-blue, 442 nm) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, male and female mice were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed at 24 hours.Results:Exposure to long wavelength red light resulted in a significant reduction in infarct volume following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p
Abstract WMP76: Trends in ischemic stroke hospitalization and outcomes in the United States pre- and peri- COVID-19 pandemic: A National Inpatient Sample study
Stroke, Volume 56, Issue Suppl_1, Page AWMP76-AWMP76, February 1, 2025. Importance:The COVID-19 pandemic significantly disrupted healthcare systems worldwide, impacting the management of acute ischemic stroke (AIS). Understanding changes in AIS admissions, treatment patterns&outcomes during the pandemic is essential for optimizing stroke care in future public health crises.Objective:To evaluate the impact of the COVID-19 pandemic on AIS admissions, treatment utilization, complications&outcomes in the U.S. from 2016 to 2021, focusing on the pre-pandemic (2016-2019)&peri-pandemic (2020-2021) periods.Methods:A retrospective observational cohort study utilizing the National Inpatient Sample (NIS) nationwide database, analyzing weighted hospital discharge records over 6 years, encompassing urban, rural, teaching &non-teaching hospitals.Participants were AIS patients aged 18 years&older (n=3,154,154), identified using ICD-10 codes. Sociodemographic characteristics such as age, sex, race&comorbidities were evaluated. The mean patient age was 70.0 ± 0.03 years, with an average length of stay of 5.1 ± 0.01 days&an adjusted mean cost of $16,765 ± 71. Men accounted for 50.5% of the cohort. AIS hospitalizations from 2016 to 2021 were collected, comparing pre-&peri-pandemic periods. Primary outcomes included AIS admission trends, while secondary outcomes included reperfusion therapy utilization, intubation&ventilation rates, discharge disposition&complications.Results:AIS admissions increased from 507,920 in 2016 to 535,694 in 2021. A demographic shift was observed, with the proportion of male patients rising from 49.8% to 51.4%&the mean age decreasing from 70.3 to 69.7 years (p < 0.0001). Most patients were White (69.5% in 2016), but their proportion decreased over time, while Black, Hispanic&Asian/Pacific Islander cases increased (p 0.5734). Reperfusion therapy usage increased, with mechanical thrombectomy (MT) rising from 2.2% to 5.6% in 6 years. Intubation/ventilation rates grew from 4.8% pre-COVID to 5.5% peri-COVID (p < 0.0001). Subarachnoid&intracerebral hemorrhage rates had increased throughout the 6 years in the group with MT-only intervention (p .011&.002, respectively).Conclusions:The COVID-19 pandemic led to significant shifts in AIS hospitalization patterns, including changes in age distribution, increased reperfusion therapy use&rising complications. These findings highlight the need for adaptive public health strategies&resource allocation to maintain stroke care during future crises.
Abstract WP392: Effects of Ripk2 Genetic Deficiency on Long-term Ischemic Stroke Outcomes in Aged Mice
Stroke, Volume 56, Issue Suppl_1, Page AWP392-AWP392, February 1, 2025. Receptor-interacting serine-threonine protein kinase 2 (Ripk2) is a key enzyme in inflammatory signaling. Ripk2 has been shown to act through pattern recognition receptors that respond to bacterial endotoxins and damage-associated molecular patterns, triggering inflammatory cascades including TAK1, NF-κB, and MAPK pathways. Recent work has implicated Ripk2 as a therapeutic target in several inflammatory disease states, such as inflammatory bowel disease and autoimmune diseases like lupus and multiple sclerosis. In our lab, we have shown that Ripk2 contributes to secondary injury following ischemic stroke due to neuroinflammation. Previous work in our lab has shown that both global knockout and microglia-specific knockout ofRipk2in young mice are protective following stroke, resulting in smaller infarct size and fewer neurological deficits. Additionally, pharmacologically inhibiting Ripk2 is neuroprotective and reduces infarction and deficits after stroke. However, the impact ofRipk2deficiency on stroke outcomes in aged mice is unknown. We utilizedRipk2knockout (Ripk2-/-) mice and wildtype (WT) mice (19-20 months old) and subjected them to permanent middle cerebral artery occlusion (pMCAO). Behavior tests were conducted for 28 days following pMCAO for longitudinal assessment ofRipk2deficiency on sensorimotor and cognitive deficits. These included the open field test, weight grip test, vertical grid test, novel object recognition test, cylinder test, and Y-maze.Ripk2-/-mice performed better than WT controls on the vertical grid test on days 1, 3, 8, 15, and 22 (p
Abstract WMP93: Long-term Outcomes of Total endovascular Reconstruction of Symptomatic Internal Carotid Artery Chronic Total Occlusions: An 18-year Experience
Stroke, Volume 56, Issue Suppl_1, Page AWMP93-AWMP93, February 1, 2025. Background:Chronic total internal carotid artery occlusion (CTO) can be associated with a high (22-25%) annual risk of stroke with limited therapeutic options. Total endovascular reconstruction (TER) is increasingly feasible but mid-term and long-term outcomes have not been reported.Methods:Data from all patients treated with carotid CTO treated with TER over the past 18years were collected in a database. Patients were selected based on the presence of angiographically proven symptomatic carotid occlusion, adequate landing zone and concurrent impairment of cerebrovascular reserve or recurrent ischemia despite maximal medical therapy. They were treated via a femoral approach using conventional CTO techniques with balloon expandable and/or self-expanding stents. Neurological evaluation of NIHSS, mRankin and carotid U/S were performed at discharge, 30days, and all subsequent follow-up. All TIA, stroke, death, and MI were recorded during follow-up. Angiographic follow-up was performed between 6-12months when possible.Results:Twenty-six symptomatic patients with a mean age of 65±7.8years were treated. Technical success was achieved in 22/26 (85%) on first attempt and in 3/4 on second attempt for total success rate of 25/26(96%). Total 30-day stroke/death/MI was 6.9% (2 ICH, both in first 3 years of experience). There were no recurrent events during 15.2±9.8months (median 12) of follow-up. Restenosis was found in 5/26 (19.2%) of patients; 2/5 were in unstented segments of the ICA. There was one case of asymptomatic carotid occlusion at 7months. The median mRS dropped from 2 to 1 at follow-up.Conclusion:TER is feasible in most patients with carotid CTO and is associated with a 30-day event rate lower than reported for STA-MCA bypass surgery. It is associated with good long-term stroke reduction despite a 19.2% risk of restenosis. Carotid re-occlusion is rare. Randomized trials are needed to validate this approach.
Abstract WP373: Physical Exercise Post-Cardiac Arrest Mitigates Long- and Short-Term Memory Deficits
Stroke, Volume 56, Issue Suppl_1, Page AWP373-AWP373, February 1, 2025. Cardiac arrest (CA) often leads to severe memory impairment, largely due to extensive neuronal loss in brain areas critical for cognitive function, including the hippocampus and amygdala. We demonstrated that physical exercise (PE) following asphyxia CA (ACA) mitigates contextual memory deficits in male rats. Intriguingly, this effect occurs without direct protection of the hippocampus and amygdala, as evidenced by significant cell death in both regions. Instead, PE post-ACA reduces neuronal loss in the medial septum (MS), a forebrain structure essential for regulating limbic system oscillations, and thus memory. This study aims to investigate whether PE post-ACA preserves oscillatory activity within the limbic circuitry and whether it ameliorates other forms of cognitive deficits in both sexes.Methods:Male and female rats are subjected to 8’ ACA. After 5 days of recovery, the animals undergo 5 consecutive days of treadmill running, followed by a battery of cognitive tests. Approximately one-month post-ACA, the animals are anesthetized with urethane for in vivo oscillatory recordings.Results:Having acquired fear conditioning (Figs. 1a and 1d), the animals were tested for cued fear memory and extinction two days later. Post-ACA exercised animals displayed a significant increase in freezing levels compared to non-exercised animals in response to a single re-exposure to the tone, indicating preserved cued fear memory (Fig. 1c). After continuous tone presentations, only the exercised animals displayed a significant decrease in freezing, suggesting they were able to extinguish their fear response (Fig. 1f). The Y-maze test revealed a significant increase in spontaneous alternation in exercised animals (Fig. 1g), indicating improved working memory. These outcomes were not influenced by locomotion (Fig. 1h) or anxiety (Fig. 1i), as confirmed by the open field test. We are currently performing the oscillatory recordings in different limbic system regions.Conclusion:PE post-ACA mitigates different forms of long- and short-term memory deficits in both sexes. This improvement is likely mediated by the preservation of oscillatory power in the MS and hippocampus (to be confirmed), highlighting a potential mechanism by which PE exerts its neuroprotective effects.