Distal Middle Cerebral Artery Research Articles

Endovascular Thrombectomy in Patients With Acute Ischemic Stroke With Simultaneous Multivessel Occlusions

Background Simultaneous multivessel occlusions (MVOs) are a rare condition, which may be encountered during endovascular thrombectomy (EVT) for acute ischemic stroke. This study aimed to investigate the prevalence, associated factors, and outcome of patients with acute ischemic stroke and MVO who underwent EVT. Methods Consecutive patients with acute ischemic stroke who received EVT between September 2014 and April 2021 were included. Acute MVO was defined as simultaneous occlusions of ≥2 intracranial or extracranial major vessels in either bilateral anterior circulation or anterior plus posterior circulation. Patients’ baseline characteristics and outcome of MVO were analyzed. Results Of 602 patients with acute ischemic stroke (mean age, 71±13 years; male, 53.1%) who received EVT, 11 patients (1.8%) had acute MVO. The involved vessels included bilateral internal carotid arteries in 3, bilateral middle cerebral arteries in 4, vertebral artery and distal middle cerebral artery in 1, and internal carotid artery and distal posterior cerebral artery in 3 patients. Preadmission dependence (modified Rankin scale score >2), higher initial stroke severity, and posterior cerebral artery occlusion were more frequently found in MVO. The cause of MVO included large vessel atherosclerosis in 4, cardioembolic in 4, cancer‐related hypercoagulability in 2, and postpartum in 1 patient. Several patients had received simultaneous multitargeted EVT, but only 4 of them achieved optimal reperfusion in both vessels. Compared with patients without MVO, those with MVO had higher mortality (adjusted odds ratio, 6.75; 95% CI, 1.93–23.6) and poor functional outcome (common odds ratio for 1‐point improvement at modified Rankin scale, 0.14, 95% CI, 0.05–0.45) at 90 days. Conclusion Acute simultaneous MVO in patients who underwent EVT is a rare yet devastating condition. Multitarget mechanical thrombectomy to achieve reperfusion is challenging but still possible.

CADASIL mutations sensitize the brain to ischemia via spreading depolarizations and abnormal extracellular potassium homeostasis.

Cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most common monogenic form of small vessel disease characterized by migraine with aura, leukoaraiosis, strokes, and dementia. CADASIL mutations cause cerebrovascular dysfunction in both animal models and humans. Here, we showed that 2 different human CADASIL mutations (Notch3 R90C or R169C) worsen ischemic stroke outcomes in transgenic mice; this was explained by the higher blood flow threshold to maintain tissue viability compared with that in wild type (WT) mice. Both mutants developed larger infarcts and worse neurological deficits compared with WT mice, regardless of age or sex after filament middle cerebral artery occlusion. However, full-field laser speckle flowmetry during distal middle cerebral artery occlusion showed comparable perfusion deficits in mutants and their respective WT controls. Circle of Willis anatomy and pial collateralization also did not differ among the genotypes. In contrast, mutants had a higher cerebral blood flow threshold, below which infarction ensued, suggesting increased sensitivity of brain tissue to ischemia. Electrophysiological recordings revealed a 1.5- to 2-fold higher frequency of peri-infarct spreading depolarizations in CADASIL mutants. Higher extracellular K+ elevations during spreading depolarizations in the mutants implicated a defect in extracellular K+ clearance. Altogether, these data reveal a mechanism of enhanced vulnerability to ischemic injury linked to abnormal extracellular ion homeostasis and susceptibility to ischemic depolarizations in CADASIL.

Salvage Superficial Temporal Artery to Middle Cerebral Artery Direct Bypass Using an Interposition Graft for Failed Encephaloduroarteriosynangiosis in Moyamoya Disease

Moyamoya disease may present with either hemorrhagic or ischemic strokes. Surgical bypass has previously demonstrated superiority when compared to natural history and medical treatment alone. The best bypass option (direct vs. indirect), however, remains controversial in regard to adult ischemic symptomatic moyamoya disease. Multiple studies have demonstrated clinical as well as angiographic effectiveness of direct bypass in adult hemorrhagic moyamoya disease. In particular, there are limited data regarding strategies in the setting of failed indirect bypass with recurrent hemorrhagic strokes. Here, we describe a salvage procedure. We describe a case of a 52-year-old man who presented with hemorrhagic moyamoya disease and failed previous bilateral encephaloduroarteriosynangiosis (EDAS) procedures at an outside institution. On a 3-year follow-up diagnostic cerebral angiogram, no synangiosis was noted on the right side and only minimal synangiosis was present on the left. The left hemisphere was significant for a left parietal hypoperfusion state. We performed a salvage left proximal superficial temporal artery to distal parietal M4 middle cerebral artery bypass using the descending branch of the lateral circumflex artery as an interposition graft with preservation of the existing EDAS sites. The patient underwent the procedure successfully and recovered well with resolution of headaches and no further strokes or hemorrhages on the 1-year follow-up magnetic resonance imaging of the brain. This case presents the use of a salvage direct bypass technique for recurrent symptomatic hemorrhagic moyamoya disease after failed EDAS. The strategy, approach, and technical nuances of this unique case have implications for revascularization options.

Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice

Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2−/− astrocytes. Inducing re-expression of truncated LCN2(Δ2–20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2−/− mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke.

Dual antiplatelet therapy improves functional recovery and inhibits inflammation after cerebral ischemia/reperfusion injury

BackgroundDual antiplatelet therapy with aspirin and clopidogrel (ASA + CPG) during the first 21 days has been shown to reduce the risk of major ischemic events in patients with transient ischemic attack (TIA) or minor stroke. However, the mechanisms underlying combination treatment with ASA + CPG in experimental ischemic stroke has not been fully elucidated.MethodsMinor cerebral ischemia was induced in mice by transient distal middle cerebral artery occlusion (tdMCAO). Two doses of ASA + CPG (12 and 24 mg/kg/day) or vehicle were administered by gavage daily. Neurological behaviors were assessed using the modified Garcia scores, Rotarod test, Y maze, and open field test. Platelet function was assessed in vitro by flow cytometry and in vivo by bleeding and clotting time. The neutrophil ratio and the levels of inflammatory cytokines were measured by flow cytometry and the Meso Scale Discovery (MSD) electrochemilunimescence, respectively.ResultsSensorimotor function was partially recovered with ASA + CPG treatment after ischemia. Anxiety levels and cognitive functions showed improvement in the ASA + CPG group at 12 mg/kg/day after 21 days. Both tail bleeding time and flow cytometry showed significantly decreased platelet function after ASA + CPG treatment. Notably, ASA + CPG at 12 mg/kg/day prolonged clotting time at 28 days after injury. Furthermore, the ratio of neutrophils, an indicator of inflammation, was reduced with 12 mg/kg/day ASA + CPG treatment in the bone marrow (BM) at 21 days and in the peripheral blood (PB) at 21 and 28 days after tdMCAO. Both doses of ASA + CPG decreased pro-inflammatory cytokine interleukin (IL)-6 expression 21 days after stroke. Taken together, these results demonstrated that combination treatment with ASA + CPG improved long-term neurological function after stroke and may inhibit platelet-neutrophil interaction by decreasing the concentration of pro-inflammatory cytokine, IL-6.ConclusionsThese findings indicate a neuroprotective effect of combination treatment with ASA + CPG for a duration of 21 days in an experimental acute minor stroke model. These findings provide further evidence that dual antiplatelet therapy may be a viable neuroprotective treatment to decrease the recurrence of stroke.

Iron promotes neurological function recovery in mice with ischemic stroke through endogenous repair mechanisms

The endogenous repair mechanisms play an important role in the recovery of nerve function after stroke, such as gliosis, synaptic plasticity, remyelination and nerve regeneration. Iron is the most abundant trace metal element in the brain and plays a crucial role in the maintenance of normal cerebral function. It is an important coenzyme factor in the process of cell metabolism, DNA synthesis, purine catabolism and neurotransmitter synthesis and decomposition. However, it is unclear what role iron plays in the long-term recovery of neurological function after stroke. In this study, we first observed that changes in iron metabolism occurred during neurological function recovery in the mice with distal middle cerebral artery occlusion (dMCAO). Our data showed that plasticity changes due to endogenous repair mechanisms resulted in improvements in cerebral cortex function. These changes involved gliosis, synaptic function reconstruction, remyelination, and activation of neural stem cells. In order to examine the potential role of iron, we synthesized liposomal-encapsulated deferoxamine (DFO) nanoparticles to further explore the effect and the mechanism of iron on the recovery of neurological function in dMCAO mice. Our results showed that liposome-DFO decreased iron deposition and reversed plasticity changes in cerebral cortex function after stroke, which delayed neurological function recovery. This experiment shows that the increasing iron level promotes endogenous repair in ischemic stroke. Our finding reveals the change regularity of iron and emphasizes the beneficial role of iron in the recovery process of neurological function, which provides an important basis for the prevention and/or treatment of ischemia-reperfusion and recovery after stroke.

Ischemic stroke following STA-MCA double bypass.

ObjectivesThe surgical technique of STA–MCA double bypass is used to improve blood flow supplied by the distal middle cerebral artery (MCA) to the cerebral territory. This retrospective study from a single center aimed to compare the outcomes following STA–MCA double bypass in 12 patients with recurrent ischemic stroke.Materials and methodsWe retrospectively analyzed the data from patients with internal carotid artery occlusion (ICAO) who had undergone STA–MCA double bypass in our center from January 2016 to December 2020. The surgical indications, evaluation of circle of Willis (CoW), changes in cerebral hemodynamic, surgical results, and follow-up results were analyzed.ResultsPost-operative perfusion-weighted imaging showed hemodynamic improvement in all 12 patients. Ten patients (83.33%) showed clinical improvement, and 2 patients (16.67%) had stable disease. No intracranial infections or acute ischemic events occurred. The post-operative National Institutes of Health Stroke Scale score and modified Barther scores were significantly improved after 180 days of follow-up. Twenty three (96%) anastomoses maintain patency of their bypass vessels, and none had recurrent cerebral infarction during a minimum of 36 months follow-up.ConclusionIn this small study, in patients with recurrent ischemic stroke without other types of treatment, STA–MCA double bypass surgery was more effective in the subgroup of patients with ICAO and poor blood supply to the CoW and an area of cerebral hypoperfusion that exceeded the area supplied by the MCA.

Corticotropin-Releasing Factor Aggravates Ischemic Stroke Injury by the Inflammatory Activation of Microglia.

Ischemic stroke is the second leading cause of death worldwide. Therefore, exploring effective and emerging molecular targets for ischemic stroke is a primary task of basic and clinical research. The aim of the present study was to investigate the function of corticotropin-releasing factor (CRF) in ischemic stroke and its related mechanisms, to provide a reference for the treatment of ischemic stroke. CRF, antalarmin, or astressin-2B were used to activate or block the CRF1 (CRF receptor 1) or CRF2 (CRF receptor 2) in BV2 cells and adult male mice, thus constructing a distal middle cerebral artery occlusion (dMCAO) model. CRF not only accelerated microglial activity by promoting transcription and production of inflammatory factors, but also promoted the transformation of activated BV2 cells from a neuroprotective phenotype (M2) to cytotoxic phenotype (M1), and these effects were mediated by the TLR4/NF-κB signaling pathway. These effects can be blocked by antalarmin but not by astressin-2B. CRF significantly aggravated the neurological deficit, increased infarction volume, and exacerbated neuronal injuries. Additionally, CRF significantly improved the levels of TNF-α and phospho-NF-κB in the ischemia penumbra. Finally, CRF significantly increased the number of CD16/Iba-1-positive cells and decreased the number of CD206/Iba-1-positive cells in the ischemia penumbra. These results provide evidence of the proinflammatory role of CRF in an ischemic stroke model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for ischemic stroke.

Hemorrhagic Transformation after Intravenous Tissue Plasminogen Activator Administration in Acute Distal Middle Cerebral Artery Occlusion.

Atrial fibrillation and cerebral embolism are known to increase the risk of hemorrhagic transformation (HT). In addition, a sufficient number of collateral vessels in acute ischemic stroke can maintain the ischemic penumbra and prevent progression to the ischemic core, while an insufficient number of collateral vessels increase the HT risk after therapeutic recanalization. In this case, when the middle cerebral artery is recanalized, reperfusion injury may occur in the basal ganglia due to insufficient collateral vessels.

Abstract TP235: Delayed FGF21 Administration Improves Cerebrovascular Remodeling And White Matter Repair After Focal Stroke In Diabetic Mice

Introduction: Type 2 diabetes mellitus (T2DM) is a major comorbidity exacerbating ischemic brain injury and impairing post-stroke recovery. Our previous study suggested that recombinant human fibroblast growth factor (rFGF) 21 might be a potent therapeutic targeting multiple aspects of pathophysiology in T2DM stroke. As a continuation of our previous work investigating the therapeutic effects of rFGF21 in T2DM stroke, this study aims to evaluate the potential effects of rFGF21 on cerebrovascular remodeling during a delayed phase after T2DM stroke. Methods: Permanent distal middle cerebral artery occlusion was performed in heterozygous non-diabetic db/+ and homozygous diabetic db/db mice. Daily rFGF21 administration was initiated one week after stroke induction and maintained for up to two weeks thereafter. Multiple markers associated with post-stroke recovery, including angiogenesis, oligodendrogenesis, white matter integrity and neurogenesis, were assessed up to three weeks after stroke. Results: Our results showed an impairment in post-stroke vascular remodeling under T2DM condition, reflected by the decreased expression of trophic factors in brain microvessels and impairments of angiogenesis. The defected cerebrovascular remodeling was accompanied by the decreased oligodendrogenesis and neurogenesis. However, delayed rFGF21 administration normalized post-stroke hyperglycemia and improved neurological outcomes, which may partially via the promotion of pro-angiogenic trophic factor expression in brain microvessels and cerebrovascular remodeling. The better cerebrovascular remodeling may also contribute to oligodendrogenesis, white matter integrity and neurogenesis after T2DM stroke. Conclusion: Delayed rFGF21 administration may improve neurological outcomes in T2DM stroke mice, at least in part by normalizing the metabolic abnormalities and promoting cerebrovascular remodeling and white matter repair.

IKKα contributes to ischemia-induced autophagy after acute cerebral ischemic injury.

BackgroundThe function of IκB kinase α (IKKα) in the brain is largely unknown. This study examined the effects of IKKα on autophagy after cerebral ischemia.MethodsPermanent distal middle cerebral artery occlusion (dMCAO) was conducted in C57/BL6 mice. Oxygen-glucose deprivation/reperfusion (OGD/R) was performed to mimic ischemia injury in neuro-2A (N2A) cells in vitro. Autophagy activation was assessed by detecting the ratio of microtubule-associated protein 1 light chain 3β (LC3B)-II/LC3B-I and Cyto-ID autophagic fluorescence. The infarct volume was verified by 2,3,5-triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI). Neurological functions were evaluated using the modified Garcia test. Cell death after dMCAO was confirmed with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. To determine the role of IKKα, small interfering RNA (siRNA) was transfected into N2A cells or injected intracerebroventricularly.ResultsIKKα and LC3B II/I expression levels were increased both in OGD/R treated N2A cells and dMCAO mice. Under the same conditions, IKKβ expression was not altered. IKKα siRNA significantly decreased the infarct volume and the apparent diffusion coefficient (ADC) related to brain edema, and promoted the neurological outcomes after dMCAO. Furthermore, inhibition of IKKα attenuated ischemia- induced the conversion of LC3B I to LC3B II both in vitro and in vivo. In addition, IKKα siRNA alleviated the formation of autophagic vacuoles and LC3 positive puncta after cerebral ischemia.ConclusionsThese findings indicate that IKKα, but not IKKβ, plays a critical role in ischemia-induced autophagy. Inhibition of IKKα protects the brain from ischemia injury and this may have potential benefits in stroke therapy.

Abstract WP247: Two Novel Interferon Signaling Proteins (Ifi27l2a And Ifitm3) Regulate Microglial Inflammation With Brain Aging And Following Stroke.

Interferon signaling drives neuroinflammation in AD and stroke. Microglia (MG) play a critical role in initiating and spreading inflammation and are involved in the chronic recovery phase following stroke. We compared the MG transcriptomic response to stroke in young and aged mice by single-cell RNA sequencing (scRNAseq) to identify novel key players in inflammation. Methods: Permanent distal middle cerebral artery occlusion (pdMCAO) or sham surgery was performed in young and aged mice (3 & 20 months). scRNAseq was performed to define the transcriptional signature in brains at 14-days after stroke versus sham surgery. Primary MG culture was used to compare the mRNA levels of Ifi27l2a and Ifitm3 after cytokine treatment. We used qRT-PCR to validate scRNAseq findings and compare specific MG genes. Results: Using comprehensive scRNAseq analysis, our unbiased approach identified Ifi27l2a and Ifitm3 as the most highly up-regulated genes in aged MG following stroke. Further analysis showed a positive correlation between Ifi27l2a and Ifitm3 in MG ( R =0.4, p<0.001) as well as in all cells. Our qRT-PCR results validated scRNAseq findings and further showed that Ifi27l2a was significantly up-regulated in the thalamus of aged brains (p=0.04; n=4 young/aged). Expression was increased in cortex, but below significance level (p=0.23). We also found upregulation of Ifitm3 in brain at PSD 3 ( p =0.01), and trending at PSD 14 ( p =0.08) (n=5-6 stroke vs. sham). In contrast, Ifitm1 and Ifitm2 were not changed. Interestingly, Ifitm3 was recently proposed as an activator to γ-secretase. In vitro exposure of MG to inflammatory cytokines (TNFα and IFNγ, 6 hrs) caused significant increase in Ifi27l2a ( p =0.03, n=5-6) and Ifitm3 mRNA (p=0.02, n=5-6) compared to untreated MG. The in vitro co-expression of these genes was also well correlated ( R =0.5). Conclusions: We identified Ifi27l2a and Ifitm3 as highly up-regulated and correlated genes in MG in aging and following stroke. Our findings suggest that co-expression of Ifi27l2a and Ifitm3 may contribute to neuroinflammation. Further studies will be required to identify the specific functions of these genes and to determine the therapeutic potential of targeting these proteins to regulate neuroinflammation in aging and stroke.

Abstract WP246: Intraventricular Administration Of Stanniocalcin-2 Promotes Post-stroke Functional Recovery In A Translational Rodent Model

Enhancing an endogenous stem cell response is a promising approach to improve stroke recovery. We have previously shown that a conductive polymer cannula system for human stem cell delivery and electrical stimulation of the post-stroke environment increases endogenous stem cell production and improves functional recovery in a rodent model of distal middle cerebral artery occlusion (dMCAO). Transcriptomic analyses coupled with lentiviral manipulation identified stanniocalcin 2 (STC-2) as one key mediator of this functional improvement. To further investigate the role of STC-2, we intraventricularly administered recombinant STC-2 one week post-dMCAO and assessed functional recovery via vibrissae-forepaw (WP) test at 5 weeks. Our results indicate that intraventricular injection of STC-2 alone post-stroke improves functional recovery in comparison to a control and intraventricular saline group (n=10 per group, p=<0.001, see Figure 1A). Histological analyses revealed an increase in endogenous stem cells that express immature neuronal markers (doublecortin, colocalized with bromodeoxyuridine) between the subventricular zone and peri-infarct region of the STC2-treated group (n=5 per group; p=0.019, see Figure 1B). Additional studies are necessary in order to further elucidate the causative molecular mechanisms involved; however, we believe this study yields great translational potential as our results may help enable a route to augment endogenous responses in the post-stroke environment.

Abstract TP258: Assessing Post-stroke Motor Impairments Using Staircase Reaching Test

Background: Behavior tests that assess side-specific motor impairments after unilateral lesion such as focal ischemic stroke have translational applications, as 8 out of 10 stroke survivors suffer from hemiparesis. Accurate measurements of neurological functions are therefore important for assessing the effectiveness of various treatment strategies. Here, we demonstrate the feasibility of the staircase test to objectively evaluate lateralized deficits in coordinated paw reaching in adult mice after experimental stroke. Methods: A cohort of adult male C57BL/6J mice (12-14 weeks of age) were subjected to a 14-day training period, where they were kept on a 21-hour food deprivation regime and at 85-90% of their original body weight. They were then subjected to permanent distal middle cerebral artery occlusion (dMCAO, n=10). The number of steps reached and pellets grasped/eaten were evaluated at pre-stroke baseline and post-stroke days (PD) 7-8 and 14-15; behavior data from PD7-8 and PD14-15 were averaged between the two days. Brains were collected at PD16 and sections immunostained with antibodies targeting neurons (MAP2) and/or activated microglia/macrophage (CD68). Results: Mice attained a stable baseline for reaching steps and consuming pellets after a 14-day training period. At PD7-8, stroked mice showed a significant decrease in their ability to grasp/consume pellets on the affected side (right limb) compared to pre-stroke baseline (p=0.001). At PD14-15, stroked mice exhibited a significant decline in their ability to reach longer distances on the affected side (right limb), attaining only 65% of their baseline performance (p=0.006). No significant deficit was shown on the non-affected side (left limb). Conclusions: Our results show that the staircase test can detect side-specific motor deficits up to PD15 in a dMCAO model. Ongoing studies with a larger cohort are evaluating longer-term deficits up to one-month post-stroke and assessing the effects of optogenetic cortico-thalamic circuit stimulations on grasping behavior using the staircase test.

Abstract 19: Long-lasting Post-stroke Memory Dysfunction In Aged Mice Is Like Due To Exacerbated Hippocampal Inflammation And Synapses Removing

Background and Purpose: Stroke can cause memory dysfunction. Long-term memory dysfunction of mice with tibia fracture (BF)+stroke is associated with accumulation of CD68 + cells in the hippocampus, which can be alleviated by activation of alpha-7 nicotinic acetylcholine receptor (α-7 nAchR). Microglia maintain normal memory via removing excessive synapses. We hypothesize that aged mice would develop long-lasting memory dysfunction after stroke, which is associated with increased CD68 + cells and synapses removing in the hippocampi. Methods: Permanent distal middle cerebral artery occlusion (pMCAO) was performed in young (2-month-old) and aging (15-18-month-old) mice, or 6 hours before pMCAO in young mice. The memory functions were analyzed weekly for 8 weeks by Y-maze and at 8 weeks post pMCAO by NOR tests. Atrophic volumes, CD68 + cells and microglial phagocytosis of synapses were quantified at 8 weeks after pMCAO. Results: Aged mice had larger atrophic volumes, more CD68 + cells in the hippocampi ipsilateral to stroke side than young mice, and also had more CD68 + cells in the ipsilateral hippocampus than the contralateral. In Y-maze test, the aged stroke mice made fewer spontaneous alternations from 3 to 8 weeks after pMCAO than the young stroke mice and sham aged mice. In NOR test, aged stroke mice spent less time on the novel object than young stroke mice and sham aged mice. α-7 nAchR agonist treatment reduced the number of CD68 + cells in the hippocampi in the BF+stroke mice. Almost all CD68 + cells were synaptophysin positive. Therefore, increased CD68 + cells in the ipsilateral hippocampus will increase synaptic removal. Reduction of neuroinflammation could reduce synaptic loss and improve post-stroke memory function. Conclusions: Increased CD68 + cells in the hippocampus is associated with long-lasting post-stroke memory dysfunction in aged mice, and reduced neuroinflammation could improve post-stroke memory function.

Abstract WMP116: Age-related Dysfunction In Leptomeningeal Collateral Remodeling After Ischemic Stroke

Introduction: The leptomeningeal collaterals (LMCs) are specialized brain surface arterioles that interconnect the major cerebral artery territories. Good outcome following ischemic stroke is highly correlated with high collateral number and function. Unfortunately, with aging and disease, the LMCs demonstrate impaired dilatory capacity, reduced vessel diameter, and even complete vessel loss (rarefaction). The present study examined the chronic remodeling capacity of LMCs following permanent stroke in young and aged mice. Methods: Young and aged C57BL6 mice (5 and 20 months) were subjected to permanent distal middle cerebral artery occlusion (pdMCAO). At 2 weeks or 3 months, LMCs were evaluated for inner diameter and VWF expression (% LMC coverage). We compared the LMCs feeding the occluded MCA territory (LMC ipsi) to the contralateral equivalent vessels (LMC contra). Diameter change is reported as fold change relative to the distal-most arteriole (DMA) associated with each LMC. Results: Young male mice demonstrated increased diameter of LMC ipsi relative to DMA at both 2 weeks (1.36 ± 0.075; n=24 vessels/4 mice, P<0.01) and 3 months after stroke (1.27 ± 0.073, n=19 vessels/2 mice, P<0.01). LMC contra were 0.901 ± 0.064 and 1.01 ± 0.053 for the same time points (n=19 and 10 vessels, P=NS). VWF expression was significantly increased in LMC ipsi at 2 weeks (ipsi 10.9 ± 2.87 vs. contra 2.91 ± 0.82, P<0.05) and neared significance at 3 months (ipsi 6.45 ± 1.54 vs. contra 2.06 ± 0.264, P=0.051). Aged mice demonstrated increased diameter of LMC ipsi relative to DMA at 2 weeks (1.24 ± 0.052, n=25 vessels from 3 mice, P<0.01), but not at 3 months (1.08 ± 0.044, n=14 from 2 mice, P=NS). Notably, the 3 month LMC ipsi vessels demonstrated irregular diameter and characteristics of rarefaction. LMC contra were 0.897 ± 0.032 and 0.967 ± 0.092 for the same time points (n=17 and 8 vessels, P=NS). VWF expression was significantly elevated in LMC ipsi vs. LMC contra at 2 weeks (6.74 ± 1.33 vs. 1.87 ± 0.361, P<0.01), but not at 3 months (2.27 ± 0.387 vs. 1.81 ± 0.398, P=NS). Conclusions: Our data show lasting LMC remodeling in young stroke brain, consisting of increased LMC diameter and expression of VWF. With aging, LMC remodeling is transient and evidence of LMC rarefaction is apparent by 3 months.

Abstract TP246: The Role Of Pericytes In Ischemic Stroke

Stroke is one of the leading causes of death worldwide. Loss of blood flow, typically from a blood clot that occludes the cerebral vasculature, causes ischemia, tissue death, and long-term cognitive deficits. Following stroke, the blood-brain barrier (BBB) is damaged, causing leakage of ions, molecules, toxins, and immune cells into the brain. Pericytes are a perivascular cell that is important for neurovascular growth and stability, and have been reported to both aid vascular regrowth and transdifferentiate into pro-inflammatory cells after ischemic injury. However, markers used to identify pericytes non-specifically label other cell types, making it unclear whether these studies are specifically identifying pericytes. In order to understand how pericytes adapt to ischemic injury, we modeled stroke in mice with distal middle cerebral artery occlusion (dMCAO) and lineage traced these cells with two novel pericyte markers: TBX18 and Atp13a5, allowing us to track ischemia-induced changes in pericytes and their progeny. We discovered that pericytes in the ischemic core die over the first three days following injury, while surviving pericytes proliferate in response to injury, and investigated how pericyte identity changes with histology and single cell RNA sequencing.

Oncotic (Myxomatous) Aneurysms: A Review of Management

AbstractAtrial myxomas are the most common primary cardiac tumors and may manifest with neurological symptoms in ∼ 30% of cases. Cerebral ischemia, aneurysmal formation, and extravascular metastases are mechanisms that lead to these neurological manifestations. Perilesional changes on computed tomography (CT) and magnetic resonance imaging (MRI) may help in the diagnosis of myxomatous aneurysms, which are usually located in the distal middle cerebral artery (MCA) and in the posterior cerebral artery (PCA) circulation territories. Careful resection of the cardiac lesion is essential for preventing embolism. However, treatment of myxomatous aneurysms is controversial due to the limited understanding of the natural history of this condition. Treatment may include clinical observation in asymptomatic patients, surgical resection, endovascular approaches, adjuvant chemotherapy, and low-dose radiation therapy. We present one case of a female patient with myxomatous aneurysm secondary to an atrial myxoma who presented with neurological symptoms and another case of a female patient who developed neurological symptoms after initial surgical treatment of the primary lesion. Lesion growth rate, topography, morphology, and the patient's clinical condition must be considered when choosing a therapeutical method. Further clinical studies are needed to achieve a better understanding and treatment of this disease.

Unilateral Terson Syndrome Following Distal Middle Cerebral Artery Aneurysm Rupture.

Unilateral Terson Syndrome Following Distal Middle Cerebral Artery Aneurysm Rupture.

Mycotic Aneurysm from Abiotrophia Defectiva Causing Subdural Hematoma with Herniation

This case describes a ruptured mycotic aneurysm from Abiotrophia defectiva that led to a subdural hematoma and subsequent herniation. In the current literature, there have been cases highlighting mycotic aneurysms leading to subdural hematoma. Several others describe similar topics; however, none were caused by Abiotrophia defectiva, leading to a herniation event. Abiotrophia defectiva, while not common, is an insidious bacterium that is difficult to detect and leads to a poor prognosis. In their paper, Ding et al. described a hematoma formation from a ruptured aneurysm of the distal middle cerebral artery [1]. Similar cases include two instances published by Boukobza et al. [2]. These prior articles and our report summarizes that this diagnosis typically warrants careful evaluation of etiologies and close management of the patient.