Background: The fragility index (FI) is the minimum number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result to a non-significant result. We used this to measure the robustness of trials comparing carotid endarterectomy (CEA) to carotid artery stenting (CAS). Methods: A search was conducted in MEDLINE, Embase, and PubMed on RCTs comparing CEA to CAS. The trials need to have statistically significant results and dichotomous primary endpoints to be included. Results: Our literature search identified 10 RCTs which included 9382 patients (4734 CEA, 4648 CAS). The primary end points of all included trials favoured CEA over CAS. The median FI was 9.5 (interquartile range 2.25 - 21.25). All of the studies that reported lost-to-follow-up (LTFU) had LTFU greater than its fragility index, which raises concern that the missing data could change the results of the trial from statistically significant to statistically insignificant. Conclusions: A small number of events (FI, median 9.5) were required to render the results of carotid artery stenosis RCTs comparing CEA to CAS statistically insignificant. All of the studies that reported LTFU had LTFU greater than its fragility index.

This boy in mid childhood presented with a sudden, excruciating occipital headache following a week of progressive gait unsteadiness and neck-accentuated meningeal pain. CT demonstrated tetraventricular haemorrhage with early obstructive hydrocephalus and perimesencephalic subarachnoid blood. CT angiography/magnetic resonance angiography (MRA) and digital subtraction angiography revealed a cervicomedullary perimedullary arteriovenous fistula (PMAVF) supplied by the anterior and posterior spinal arteries with a single venous pouch aneurysm at C3-4. Emergency external ventricular drain (EVD) placement was performed. Definitive endovascular cure was achieved 72 hours later using simultaneous bilateral micro-catheterisation of the venous pouch and 'parallel' coiling under multimodality neuromonitoring, completely occluding the shunt while preserving spinal arterial flow. The patient recovered without any neurological deficit, the EVD was gradually weaned over the first 5 postoperative days and removed without clinical or radiological difficulty, and the 12-week MRI/MRA confirmed complete occlusion; at that time, he had returned fully to school and sports including football. This case highlights the importance of cervicomedullary vascular imaging in atraumatic paediatric Subarachnoid Hemorrhage (SAH)/intraventricular haemorrhage and illustrates that complex type III/C PMAVFs can be safely cured in a single session using a dual-pedicle coiling strategy in select cases.

BACKGROUND:Patients with stroke due to symptomatic intracranial occlusion and concurrent symptomatic high-grade cervical internal carotid artery (ICA) stenosis (≥70%) or occlusion constitute 15%-20% of patients undergoing EVT. The optimal management of the cervical ICA in these tandem lesions remains unknown. We hypothesise that acute carotid artery stenting in addition to EVT will improve functional outcomes when compared with EVT alone. STUDY DESIGN:Endovascular Acute Stroke Intervention-Tandem Occlusion (EASI-TOC) is a multicentre, prospective, randomised, open-label, blinded end-point (PROBE) controlled trial. Adult patients with a disabling acute anterior circulation stroke (intracranial carotid, M1 or M2 segment occlusion) and salvageable brain tissue who undergo EVT within 24 h of onset, are eligible for enrolment if they have an angiographically confirmed atherosclerotic carotid tandem lesion. Patients are randomised 1:1 to acute carotid stenting or no stenting during EVT. STUDY ENDPOINTS:The primary outcome is the proportion of patients achieving a favourable functional outcome (mRS 0-2) at 90 days. Secondary outcomes include 12-month mRS, recanalisation, the 90-day rate of recurrent ipsilateral stroke or retinal ischaemia, the proportion of patients with ICA thrombosis, 90-day Montreal Cognitive Assessment score and quality of life. Safety outcomes include any ICH, sICH, all-cause mortality and procedural complications. SUMMARY:Endovascular Acute Stroke Intervention-Tandem Occlusion is a pragmatic trial addressing a critical gap in the acute management of patients with tandem carotid lesions by evaluating whether acute carotid stenting provides a functional benefit over no stenting in patients undergoing EVT. TRIAL REGISTRATION:ClinicalTrials.gov NCT04261478.

Importance:Chronic subdural hematomas commonly recur after surgical drainage. The effect of adjunctive embolization of the middle meningeal artery (EMMA) on recurrence risk remains unclear. Objective:To evaluate whether EMMA as an adjunct to surgical drainage reduces chronic subdural hematoma recurrence compared with surgery alone. Design, Setting, and Participants:This trial was a randomized, open-label, blinded-end point trial involving adults with unilateral, symptomatic chronic subdural hematoma (≥10 mm) undergoing surgical drainage across 9 tertiary care centers in Canada between August 2021 and April 2025. Intervention:EMMA using a liquid embolic agent (Onyx-18) within 72 hours after surgical drainage vs a control group that did not receive EMMA after surgical drainage. Main Outcomes and Measures:Primary outcome was symptomatic recurrence of chronic subdural hematoma detected on computed tomographic (CT) scan at 90 days (range, 60 to 120 days). Secondary outcomes included radiographic recurrence of chronic subdural hematoma, 90-day mortality, and serious adverse events. The last date of follow-up was July 27, 2025. Results:Of 192 randomized participants, 186 (mean age, 71.8 years; 136 male [73%]) completed the trial (93 per group). The primary outcome of symptomatic recurrence of chronic subdural hematoma detected on CT scan occurred in 4 participants (4.3%) in the EMMA group vs 26 patients (28%) in the control group (risk difference, -23.7; 95% CI, -34.1 to -13.9; P < .001). Radiographic recurrence occurred in 13 participants (14%) in the EMMA group vs 46 patients (49.5%) in the control group. Mortality was 4.3% vs 1.1%; serious adverse events occurred in 8.6% vs 5.4%, respectively. Conclusions and Relevance:Adjunctive EMMA after surgical drainage significantly reduced symptomatic recurrence on CT scan of unilateral chronic subdural hematoma at 90 days compared with surgery alone. Trial Registration:ClinicalTrials.gov Identifier: NCT04750200.

Importance Chronic subdural hematomas commonly recur after surgical drainage. The effect of adjunctive embolization of the middle meningeal artery (EMMA) on recurrence risk remains unclear. Objective To evaluate whether EMMA as an adjunct to surgical drainage reduces chronic subdural hematoma recurrence compared with surgery alone. Design, Setting, and Participants This trial was a randomized, open-label, blinded–end point trial involving adults with unilateral, symptomatic chronic subdural hematoma (≥10 mm) undergoing surgical drainage across 9 tertiary care centers in Canada between August 2021 and April 2025. Intervention EMMA using a liquid embolic agent (Onyx-18) within 72 hours after surgical drainage vs a control group that did not receive EMMA after surgical drainage. Main Outcomes and Measures Primary outcome was symptomatic recurrence of chronic subdural hematoma detected on computed tomographic (CT) scan at 90 days (range, 60 to 120 days). Secondary outcomes included radiographic recurrence of chronic subdural hematoma, 90-day mortality, and serious adverse events. The last date of follow-up was July 27, 2025. Results Of 192 randomized participants, 186 (mean age, 71.8 years; 136 male [73%]) completed the trial (93 per group). The primary outcome of symptomatic recurrence of chronic subdural hematoma detected on CT scan occurred in 4 participants (4.3%) in the EMMA group vs 26 patients (28%) in the control group (risk difference, −23.7; 95% CI, −34.1 to −13.9; P < .001). Radiographic recurrence occurred in 13 participants (14%) in the EMMA group vs 46 patients (49.5%) in the control group. Mortality was 4.3% vs 1.1%; serious adverse events occurred in 8.6% vs 5.4%, respectively. Conclusions and Relevance Adjunctive EMMA after surgical drainage significantly reduced symptomatic recurrence on CT scan of unilateral chronic subdural hematoma at 90 days compared with surgery alone. Trial Registration ClinicalTrials.gov Identifier: NCT04750200

Three-dimensional (3D) bioprinting offers transformative potential for cardiac tissue engineering by enabling the fabrication of cell-laden constructs. However, key challenges remain, including maintaining cell viability within bioprinted constructs and understanding how embedded cells affect their physical and mechanical properties.This study addresses these challenges by incorporating human umbilical vein endothelial cells (HUVECs) into alginate-gelatin hydrogels and evaluating their impact on mechanical, physical, and rheological properties. Bioinks or hydrogels were prepared with or without HUVECs, and their rheological properties were assessed. Computational fluid dynamics (CFD) simulation was employed to determine the appropriate bioprinting pressure while minimizing cell damage. Constructs were designed and 3D-printed with an angular pattern to replicate the orientation of cardiac myofibrils and were characterized over a 21-day period for viscoelasticity, elastic modulus, swelling, mass loss, morphology, and cell viability.The incorporation of cells increased the storage and loss moduli of the bioink, demonstrating shear-thinning behavior as described by the Cross model. CFD simulation combined with preliminary cell viability assays identified 25 kPa as a suitable 3D-printing pressure, effectively preserving cell viability. Both cell-free and cell-laden constructs exhibited viscoelastic properties; however, cell-laden constructs displayed a lower elastic modulus under linear compression, reduced swelling, and greater mass retention. High cell viability was observed immediately post-bioprinting and was maintained for more than 1 week. These findings provide a framework for developing structurally robust, cell-laden constructs with enhanced functional fidelity, supporting their application in cardiac tissue engineering.

This study aimed to investigate whether reduced cerebral blood flow is associated with cortical brain remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Further, to assess whether these changes occur independently of decreased cardiac output and correlate with alternative markers of HFrEF severity. The findings suggest that brain remodelling in HFrEF can occur independently of reduced cardiac output, highlighting the importance of other pathophysiological factors. A nuanced understanding of these mechanisms could inform improved diagnostic and therapeutic strategies targeting cardiocerebral interactions.

Background Most people do not recognize symptoms of neurological and cardiac emergencies in a timely manner. This leads to delays in hospital arrival and reduced access to therapies that can open arteries. We created a smartphone app to help patients and families evaluate if symptoms may be high risk for stroke or heart attack (myocardial infarction, MI). The ECHAS (Emergency Call for Heart Attack and Stroke) app guides users to assess their risk through evidence-based questions and a test of weakness in one arm by evaluating finger-tapping on the smartphone. Objective This study is an initial step in the accuracy evaluation of the app focused on sensitivity. We evaluated whether the app provides appropriate triage advice for patients with known stroke or MI symptoms in the Emergency Department. We designed this study to evaluate the sensitivity of the app, since the most dangerous output of the app would be failure to recognize the need for emergency evaluation. Specificity is also important, but the consequences of low specificity are less dangerous than those of low sensitivity. Methods In this single-center cross-sectional study, we enrolled patients presenting with symptoms of possible stroke or MI. The ECHAS app assessment consisted of a series of evidence-based questions regarding symptoms and a test of finger-tapping speed and accuracy on the phone’s screen to detect unilateral arm weakness. The primary outcome was the sensitivity of the ECHAS app in detecting the need for ED evaluation. The secondary outcome was the sensitivity of the ECHAS app in detecting the need for hospital admission. Two independent and blinded board-certified physicians reviewed the medical record and adjudicated the appropriateness of the ED visit based on a 5-point score (ground truth). Finally, we asked patients semistructured questions about the app’s ease of use, drawbacks, and benefits. Results We enrolled 202 patients (57 with stroke and 145 with MI). The ECHAS score was strongly correlated with the ground truth appropriateness score (Spearman correlation 0.41, P<.001). The ECHAS app had a sensitivity of 0.98 for identifying patients in whom ED evaluation was appropriate. The app had a sensitivity of 1.0 for identifying patients who were admitted to the hospital because of their ED evaluation. Patients completed an app session in an average of 111 (SD 60) seconds for the stroke pathway and 60 (SD 33) seconds for the MI pathway. Patients reported that the app was easy to use and valuable for personal emergency situations at home. Conclusions The ECHAS app demonstrated a high sensitivity for the detection of patients who required emergency evaluation for symptoms of stroke or MI. This study supports the need for a study of specificity of the app, and then a prospective trial of the app in patients at increased risk of MI and stroke.

Introduction Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.Methods and analysis The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.Ethics and dissemination This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.Trial registration number NCT03559114.

Cardiac dysfunction in heart failure with reduced ejection fraction (HFrEF) may contribute to brain atrophy and cognitive decline beyond that which is typical of healthy aging. This study tested the hypothesis that HFrEF would be associated with regionally unique brain remodeling and impaired cognitive performance independent of age. Furthermore, that cardiac index and clinical markers of HFrEF severity would predict brain remodeling and cognition with age and HFrEF, respectively. Cardiac function and brain morphology were assessed using magnetic resonance imaging in young healthy adults (24 ± 6 yr), older healthy adults (60 ± 6 yr), and patients living with HFrEF (59 ± 6 yr). The Montreal Cognitive Assessment was administered to assess cognition. Gray matter volume (GMV) (young: 492 ± 24, old: 456 ± 24, HFrEF: 433 ± 32 cm3, P ≤ 0.05) and cortical thickness (young: 2.44 ± 0.07, old: 2.33 ± 0.08, HFrEF: 2.22 ± 0.10 mm, P < 0.01) were lower with age and lowered further with HFrEF. Regional analysis revealed a unique pattern of atrophy with HFrEF. Whereas age had little effect on cortical curvature (P = 0.60), it was greater in HFrEF (young: 0.127 ± 0.003, old: 0.128 ± 0.003, HFrEF: 0.136 ± 0.005 mm-1, P < 0.01). Cardiac index was the best correlate of brain atrophy and cognitive performance with age (R = 0.33-0.47; P < 0.05). However, EF and end systolic volume index were better correlates of brain atrophy and cognitive performance in HFrEF (R = -0.50-0.49; P ≤ 0.05). These data indicate that lower GMV and cortical thickness in HFrEF are not merely an acceleration of age-related declines but reflect a unique pattern of brain atrophy and remodeling. In addition, classic markers of HF severity may be better predictors of pathological brain remodeling than reduced cardiac index.NEW & NOTEWORTHY Lower gray matter volume, and cortical thinning in heart failure are regionally dependent, and independent of age. Patients living with heart failure had higher cortical curvature, but older adults did not. Lower gray matter volume, cortical thinning, and cognitive impairment were associated with markers of cardiac dysfunction, with ejection fraction, and end systolic volume index being better predictors among the older and heart failure cohort than cardiac index.

Cardiac tissue engineering has been rapidly evolving with diverse applications, ranging from the repair of fibrotic tissue caused by “adverse remodeling,” to the replacement of specific segments of heart tissue, and ultimately to the creation of a whole heart. The repair or replacement of cardiac tissue often involves the development of tissue scaffolds or constructs and the subsequent assessment of their performance and functionality. For this, the design and/or selection of biomaterials, and cell types, scaffold fabrication, and in vitro characterizations are the first starting points, yet critical, to ensure success in subsequent implantation in vivo. This highlights the importance of scaffold fabrication and in vitro experiments/characterization with protocols for cardiac tissue engineering. Yet, a comprehensive and critical review of these has not been established and documented. As inspired, herein, the latest development and advances in scaffold fabrication and in vitro characterization for cardiac tissue engineering are critically reviewed, with focus on biomaterials, cell types, additive manufacturing techniques for scaffold fabrication, and common in vitro characterization techniques or methods. This article would be of benefit to the ones who are working on cardiac tissue engineering by providing insights into the scaffold fabrication and in vitro investigations.

BackgroundIncomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited. MethodsPatients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained. ResultsOf 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0-2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0-2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%). ConclusionIR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.

Element dysregulation is a pathophysiologic hallmark of ischemic stroke. Prior characterization of post-stroke element dysregulation in the photothrombotic model demonstrated significant element changes for ions that are essential for the function of the neurovascular unit. To characterize the dynamic changes during the early hyperacute phase (<6 h), we employed a temporary large-vessel occlusion stroke model. The middle cerebral artery was temporarily occluded for 30 min in male C57BL/6 mice, and coronal brain sections were prepared for histology and X-ray fluorescence microscopy from 5 to 120 min post-reperfusion. Ion dysregulation was already apparent by 5 min post-reperfusion, evidenced by reduced total potassium in the lesion. Later time points showed further dysregulation of phosphorus, calcium, copper, and zinc. By 60 min post-reperfusion, the central portion of the lesion showed pronounced element dysregulation and could be differentiated from a surrounding region of moderate dysregulation. Despite reperfusion, the lesion continued to expand dynamically with increasing severity of element dysregulation throughout the time course. Given that the earliest time point investigated already demonstrated signs of ion disruption, we anticipate such changes may be detectable even earlier. The profound ion dysregulation at the tissue level after reperfusion may contribute to hindering treatments aimed at functional recovery of the neurovascular unit.

Introduction: While timely therapy of neurologic and cardiac emergencies can improve outcomes, patients often fail to identify acute events resulting in delays in seeking emergency care. ECHAS is a smartphone application and sensor system aimed to reduce patient-related delay. We performed a retrospective study to test ECHAS in identifying patients who required emergency assessment for possible myocardial infarction (MI) or stroke. Methods: We enrolled 202 patients (57 with stroke-like, 145 MI-like symptoms) who presented to the ED at a single center in Canada. Participants answered yes-no questions about their prior history, acute symptoms, and performed a finger-tapping test on an Apple iPhone with ECHAS. Answers resulted in a risk score that guided one of the three triage decisions: 1) call 911, 2) call hotline, or 3) call your primary care physician. The ground truth for the triage decision assessment was the appropriateness of the patient’s visit to the ED. Specificity could not be calculated due to low numbers of patients who did not need emergency evaluation. Results: The mean time to complete the acute assessment was 60 seconds for MI and 111 seconds for stroke. ECHAS output recommended 66% of patients call 911, 30% hotline, and 4% primary care follow-up. The sensitivity to identify the need for emergency evaluation was 0.98. The sensitivity to identify patients who were admitted for possible MI or stroke was 1.0. A negative correlation was found between low ECHAS score and prolonged symptom onset to hospital arrival time for MI-like symptoms (r = -0.21, p < 0.05). Patients found ECHAS to be very useable (Fig 1). Conclusion: The ECHAS application was highly sensitive and easily usable in guiding patients to identify medical emergencies without input by healthcare personnel. These pilot results will drive a planned 4,000-patient prospective randomized trial to evaluate whether ECHAS will reduce times from symptom onset to first medical contact for MI and stroke.

BACKGROUND:Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS:We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS:Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS:Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.