Cerebral Artery Research Articles

Intravenous Regeneration-associated Cell Transplantation Enhances Tissue Recovery in Mice with Acute Ischemic Stroke.

Previously, we reported that transplantation of regeneration-associated cells (RACs) via the ipsilateral external carotid artery reduced stroke volume in mice with permanent occlusion of the middle cerebral artery (MCA). However, intracarotid arterial transplantation is invasive and requires skill, and severe complications may occur, such as thromboembolism, infection, and decreased cerebral blood flow. This study aimed to investigate the efficacy of intravenous injection of RACs in reducing stroke volume and increasing anti-inflammatory and angiogenic factors in mice with focal cerebral ischemia. Mice with occluded MCAs received intravenous injections of phosphate-buffered saline (PBS) (control), low-dose RACs, or high-dose RACs. The proximal part of the left MCA was occluded to induce permanent focal ischemia. After 3 days, we administered PBS or low-dose (1 × 104 /50 µL) or high-dose RACs (1 × 105 /50 µL) through the tail vein and assessed the infarct volume on day 7. High-dose RACs significantly decreased infarct volume compared to PBS, whereas low-dose RACs showed no effect. The number of interleukin-10 (IL-10)-positive and vascular endothelial growth factor (VEGF)-positive cells in the peri-infarct area on day 7 was significantly higher in mice treated with low-dose and high-dose RACs than in the PBS control group. Intravenous injection of RACs can reduce ischemic stroke volume; however, a higher dose of RACs is required than the dose used in intraarterial transplantation. By assessing IL-10 and VEGF expression, the study sheds light on the underlying mechanisms of RAC therapy, revealing its potential anti-inflammatory and angiogenic properties in the treatment of cerebral ischemia.

Clinical Characteristics and Outcomes in Patients with Ruptured Middle Cerebral Artery Aneurysms: A Multicenter Study in Northern China.

The long-term prognosis of ruptured middle cerebral artery aneurysms (MCAAs) in northern China remains unclear. The aim of this study is to analyze the epidemiological characteristics and long-term outcomes of ruptured MCAAs in northern China. We included patients who were consecutively admitted for ruptured MCAAs to 12 tertiary care centers in northern China from January 2017 to December 2020. Kaplan‒Meier curves were used to compare survival in hazard strata. The Cox proportional hazards model was used to analyze risk factors and mortality risk, whereas logistic regression was used to identify factors influencing 2-year survival. Subgroup analyses were performed to verify the robustness of the results. Data on 959 patients with ruptured MCAAs were analyzed; 16.4% of these patients had ruptured intracranial aneurysms (RIAs) and were registered in the Chinese cerebral aneurysm database. The mean follow-up duration was 3.0years (range 0-6.2years). The 3-month and 2-year mortality rates were 15.5% and 18.2%, respectively. The risk factors for mortality were identified via Cox regression and were as follows: age > 70years, previous stroke, combined intracerebral hemorrhage (ICH)/intraventricular hemorrhage (IVH), poor Hunt and Hess grade, multiple aneurysms, and conservative treatment (CT). The positive association between the risk of death and CT was consistent across subgroups. According to logistic regression, hypertension, previous stroke, combined ICH/IVH, Hunt and Hess grade, and WFNS (World Federation of Neurological Surgeons) score were identified as factors negatively influencing 2-year survival. We detail the epidemiologic characteristics and long-term outcomes of MCAAs. The risk factors for mortality included age > 70years, previous stroke, combined ICH/IVH, poor Hunt and Hess grade, and multiple aneurysms. Compared with microsurgical treatment (MST), CT is associated with an increased risk of mortality, while the risk of mortality associated with endovascular treatment (EVT) is not significantly different. Two-year survival was associated with hypertension, previous stroke, ICH/IVH, and poor grades at admission.

Distance from the midline to the aneurysm as simple predictor of ischemic complication with small unruptured middle cerebral artery aneurysm surgery

BackgroundThis study aimed to clarify the risk factors for postoperative cerebral infarction in surgical clipping for prevalent small middle cerebral artery aneurysms (MCA Ans). MethodsThis retrospective study included 246 patients (mean age, 64.8 ± 10.0 years; 25.6% males, 74.4% females) with 258 aneurysms (mean aneurysm size, 5.4 ± 2.4mm) who underwent direct surgery for unruptured MCA Ans at our institution from January 2015 to December 2020. All surgeries were performed under general anesthesia, incorporating indocyanine green videoangiography and transcranial motor-evoked potentials to enhance surgical precision and safety. The occurrence of surgery-related cerebral infarction was evaluated using postoperative CT scans within one week, comparing them with preoperative images. Patients were categorized based on the presence or absence of postoperative stroke and were analyzed for age, sex, past medical history, aneurysm size, number of clips used, and distance from the midline to the aneurysm. ResultsSeventeen patients had postoperative cerebral infarction (6.6%, symptomatic 6, asymptomatic 11). There were no significant differences in terms of age, number of clips, or aneurysm size between the two groups; however, the distance from the midline to the aneurysm was significantly shorter in the stroke group (27.1 ± 4.7mm; p < 0.001), with a cutoff value of 29mm using the receiver operating characteristic curve. ConclusionSurgical clipping for MCA Ans presents a high risk of cerebral infarction for aneurysms located closer to the midline, emphasizing the importance of considering aneurysm location as a risk indication in surgical clipping.

Finding MeVO: Identifying Intracranial Medium-Vessel Occlusions at CT Angiography.

The development of methods to detect and treat intracranial large-vessel occlusions (LVOs) has revolutionized the management of acute ischemic stroke. CT angiography (CTA) of the head and neck is effective in depicting LVOs and widely used in the evaluation of patients who have had a stroke. Ongoing efforts are now focused on the potential to detect and treat intracranial medium-vessel occlusions (MeVOs), which by definition are smaller than LVOs and thus more difficult to detect with CTA. The authors review common and variant anatomies of medium-sized cerebral arteries and the appearance of a variety of MeVOs on CT angiograms. Possible pitfalls in MeVO detection include rare anatomic variants, calcified thrombi, and stump occlusions. Current recommendations for performing CTA and ancillary methods that might aid in MeVO detection are discussed. Understanding the relevant anatomy and the variety of appearances of MeVOs aids radiologists in identifying these occlusions, particularly in the setting of urgent stroke. ©RSNA, 2024 See the invited commentary by Ospel and Nguyen in this issue.

MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway

Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.

Intra-arterial contrast administration: a confounding appearance on stroke CT imaging.

A female patient in her 70s presented with mild slurred speech. Clinical assessment revealed only minor dysarthria. A stroke protocol CT study was performed comprising a non-contrast CT head, CT angiogram (CTA) and CT perfusion (CTP) imaging. Despite a normal non-contrast CT head, CTP imaging demonstrated a large left anterior circulation territory abnormality compatible with core infarct. The CTA displayed absent left middle cerebral artery opacification and an abnormal pattern of thalamic and posterior fossa structure enhancement. Following a neuroradiology review, it was identified that the contrast bolus had been administered into the right brachial artery causing direct arterial opacification of the right vertebral/carotid arteries and their distal branches. No contrast was present in the left carotids or distal left intracranial anterior circulation giving the false impression of a large vessel occlusion. The patient was subsequently discharged without receiving inappropriate reperfusion therapy. This case highlights the role of technical factors influencing CT interpretation, particularly when performed by artificial intelligence/automated analysis.

BAK ameliorated cerebral infarction/ischemia–reperfusion injury by activating AMPK/Nrf2 to inhibit TXNIP/NLRP3/caspase-1 axis

BackgroundCerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of Psoralea corylifolia Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear. MethodsMiddle cerebral artery occlusion reperfusion (MACO/R) was used to establish mouse model. The protective effect of BAK in MCAO/R mices was detected by performing neurological deficit testing, TTC staining, and H&E staining. Oxygen/glucose deprivation and reperfusion (OGD/R) was used to stimulate SH-SY5Y cells in vitro. Protein expression was detected by western blotting, gene expression was detected by quantitative real-time polymerase chain reaction and apoptosis was detected by immunofluorescence. ResultsOur study indicated that BAK protected ischemia–reperfusion injury in MACO/R mice, and upregulated superoxide dismutase (SOD) and the catalase (CAT) enzyme activity. BAK also inhibited the expression of TNF-α, IL-1β, IL-6, and IL-18 and suppressed apoptosis and pyroptosis both in MACO/R mice and in OGD/R SH-SY5Y cells. Further results showed that BAK could suppress TXNIP, ASC, NLRP3, and caspase-1 mRNA levels to reverse assembly of inflammasome. And BAK could also upregulate the expression of phosphorylated AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor (Nrf2). In addition, Nrf2 inhibitor ML385 reversed the BAK induced reduction of TXNIP, ASC, NLRP3, and the AMPK inhibitor also abolished BAK’ the effect on the regulation of Nrf2 TXNIP, ASC, NLRP3, caspase-1, and pro-inflammatory cytokines. In conclusion, BAK, found in leaves and seeds of Psoralea corylifolia Linn, could ameliorated cerebral I/R injury through activating AMPK/Nrf2 to inhibit NLRP3 inflammasome, which might present new therapeutic strategy for cerebral I/R injury.

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Ischemic stroke is the result of a permanent or transient occlusion of a brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, stroke remains the second leading cause of death worldwide. A comprehensive understanding of the complex and interconnected mechanisms, along with the endogenous mediators that modulate stroke responses is essential for the development of effective interventions. Our study investigates cortistatin, a neuropeptide extensively distributed in the immune and central nervous systems, known for its immunomodulatory properties. With neuroinflammation and peripheral immune deregulation as key pathological features of brain ischemia, cortistatin emerges as a promising therapeutic candidate. To this aim, we evaluated its potential effect in a well-established middle cerebral artery occlusion (MCAO) preclinical stroke model. Our findings indicate that the peripheral administration of cortistatin at 24h post-stroke significantly reduces neurological damage and enhances recovery. Importantly, cortistatin-induced neuroprotection was multitargeted, as it modulated the glial reactivity and astrocytic scar formation, facilitated blood-brain barrier recovery, and regulated local and systemic immune dysfunction. Surprisingly, administration of cortistatin at immediate and early post-stroke time points proved to be not beneficial and even detrimental. These results emphasize the importance of understanding the spatio-temporal dynamics of stroke pathology to develop innovative therapeutic strategies with appropriate time windows. Premature interruption of certain neuroinflammatory processes might inadvertently compromise neuroprotective mechanisms. In summary, our study highlights cortistatin as a novel pleiotropic therapeutic approach against ischemic stroke, offering new treatment options for patients for whom early revascularization intervention is unsuccessful.

Middle cerebral artery blood velocity and end-tidal carbon dioxide responses to moderate intensity cycling in children, adolescents, and adults.

This study investigated the middle cerebral artery blood velocity (MCAv) response to constant work-rate moderate-intensity cycling exercise in 21 children (9.3 ± 0.8 yr), 17 adolescents (12.3 ± 0.4 yr), and 20 young adults (23.6 ± 2.4 yr). Participants completed an incremental ramp test to exhaustion on a cycle ergometer to determine maximal oxygen uptake and gas exchange threshold (GET) before completing three 6-min transitions at a moderate intensity (90% GET) on separate visits. On each visit, bilateral MCAv was measured by transcranial Doppler ultrasonography and breath-by-breath end-tidal carbon dioxide ([Formula: see text]) via a metabolic cart. Data were ensemble-averaged for each participant and analyzed using a monoexponential model. Absolute MCAv was significantly higher throughout exercise in children and adolescents compared with adults (P < 0.001). Children had a significantly lower relative increase in MCAv from baseline (∼12%) compared with adolescents (∼20%) and adults (∼18%, P < 0.040). All adolescents and adults had a monoexponential rise in MCAv and [Formula: see text], but this was observed in only eight children. Children and adolescents had a significantly faster MCAv time constant (τ, 12 ± 6 and 14 ± 8 s, respectively) compared with adults (27 ± 9 s, P < 0.001). MCAv τ was positively associated with faster [Formula: see text] τ in adolescents (r = 0.70, P = 0.002) but not in children (r = -0.20, P = 0.640). Time- and amplitude-based response parameters of MCAv kinetics were significantly associated with [Formula: see text] kinetics in adults (r = 0.50-0.74, P ≤ 0.025), but not in children (r = -0.19 to -0.48, P > 0.227). These findings suggest that the transition from childhood to adulthood impacts the MCAv response to exercise and the relationships between [Formula: see text] and MCAv kinetics during exercise.NEW & NOTEWORTHY This is the first study to find that children have smaller increases in Δ%MCAv (∼12%) during moderate-intensity exercise compared with adolescents and adults (∼18%-20%). Furthermore, MCAv kinetics were significantly faster in children and adolescents, compared with adults. MCAv kinetic responses were significantly and positively associated with [Formula: see text] kinetics in adults, but not in children. These novel data also suggest that the regulatory role of [Formula: see text] on MCAv during exercise begins to strengthen during adolescence.

Factors associated with mortality and functional outcome after decompressive craniectomy in malignant middle cerebral artery infarction

ObjectiveIdentifying the predictive factors of mortality and functional outcomes following decompressive craniectomy (DC) surgery in patients with malignant middle cerebral artery infarction (MMCAI) is essential for decision-making regarding conservative versus surgical treatment. This study aimed to assess the mortality and functional outcomes of MMCAI patients after DC surgery and to identify the predictive factors associated with mortality and functional outcomes.MethodsA total of 76 patients with MMCAI who underwent surgical DC were included. The mortality rates and functional outcomes were assessed, and factors associated with mortality and functional outcomes were identified through univariate analysis followed by multivariate logistic regression analysis.ResultsThe mortality rate was 44.8%, while a favorable functional outcome was observed in 28.9% of the patients. modified Glasgow coma scale (GCS) before DC (OR = 0.416, 95% CI = 0.261–0.662, P < 0.001) and infarct volume before DC (OR = 1.000-1.012, 95% CI = 1.000-1.012, P = 0.037) were independent risk factors for death. Age (OR = 0.88, 95% CI = 0.812–0.952, P = 0.002), modified GCS before DC (OR = 2.477, 95% CI = 1.395-4.4, P = 0.002), and infarct volume before DC (OR = 0.987, 95% CI = 0.975–0.999, P = 0.035) were independent factors associated with favorable functional outcomes.ConclusionPreoperative modified GCS and preoperative infarct volume were independent factors associated with both mortality and functional outcomes. Age was only associated with functional outcomes.

Sex and Age-Dependent Effects of miR-15a/16-1 Antagomir on Ischemic Stroke Outcomes

Ischemic stroke is a leading cause of disability and mortality worldwide. Recently, increasing evidence implicates microRNAs (miRs) in the pathophysiology of ischemic stroke. Studies have shown that miR-15a/16-1 is abnormally expressed in brains after ischemic stroke, and its upregulation may increase ischemic damage. Given that sex and age are significant modifiers of stroke outcomes, here we investigated whether inhibiting miR-15a/16-1 with antagomirs mitigates cerebral ischemia/reperfusion (I/R) injury in a sex- and age-dependent manner. Young (3 months) and aged (18 months) male and female C57/BL mice underwent 1-h middle cerebral artery occlusion and 3–7 days reperfusion (tMCAO). We administered miR-15a/16-1 antagomir (30 pmol/g) or control antagomir (NC, 30 pmol/g) via tail vein 2 h post-MCAO. Neurobehavioral testing and infarct volume assessment were performed on days 3 and 7. Compared to controls, antagomir treatment significantly improved neurobehavioral outcomes and reduced infarct volume in tMCAO mice at day 7, with the effects being more pronounced in young mice. Notably, young female mice exhibited superior survival and sensorimotor function compared to young male mice. These results were also replicated in a permanent MCAO (pMCAO) mice model. This suggests miR-15a/16-1 antagomir and estradiol may synergistically regulate genes involved in neurovascular cell death, inflammation, and oxidative stress, with sex and age-dependent expression of miR-15a/16-1 and its targets likely underlying the observed variations. Overall, our findings identify miR-15a/16-1 antagomir as a promising therapeutic for ischemic stroke and suggest that sex and age should be considered when developing miR-based therapeutic strategies.

Association Between the Fetal‐Type Posterior Cerebral Artery and Hypertensive Thalamic Hemorrhage

ABSTRACTIntroductionThis study investigated the association between the fetal‐type posterior cerebral artery (FTP) and hypertensive thalamic hemorrhage (HTH).MethodPatients with hypertension who met the admission criteria between January 2020 and August 2022 were retrospectively analyzed and divided into the HTH and non‐HTH groups based on the presence or absence of thalamic hemorrhage, respectively. In addition to whether the variable was an FTP, other variables with unbalanced distributions between the two groups were used as matching factors for 1:1 propensity score matching, and other variables that were not used as matching factors were used as covariates for conditional logistic regression.ResultsA total of 722 patients were included in the study, with 115 in the HTH group and 607 in the non‐HTH group. After propensity score matching, 114 patients were included in both groups. The multivariate logistic regression analysis showed that the FTP (p = 0.003, odds ratio [OR]: 2.712, 95% confidence interval [CI]: 1.407–5.225) and homocysteine levels (p = 0.007; OR: 1.051; 95% CI: 1.014–1.089) were significantly correlated with the occurrence of HTH.ConclusionThe incidence of FTP is not low, and it is an independent risk factor for HTH. Early recognition and appropriate monitoring are warranted for cases of FTP.

Single-Center Experience With Endovascular Therapy in Acute Occlusion of ICAS: Preferred Stent Thrombectomy Versus Preferred Angioplasty.

The preferred endovascular therapy (EVT) for large-vessel occlusion in intracranial atherosclerosis (ICAS) is unknown. We compared the efficacy of preferred stent thrombectomy and preferred angioplasty in patients with acute large-vessel occlusion in ICAS. Data from consecutive EVT patients (May 2020 to September 2023) with acute middle cerebral artery occlusion in ICAS were retrospectively analyzed. Preferred angioplasty was performed if there was a preoperative "microcatheter first-pass effect;" otherwise, preferred stent thrombectomy was performed. Analyses were grouped according to the two EVT treatments. Clinical data of all patients, including the time from puncture to recanalization, rate of successful reperfusion, early neurological improvement, intracranial hemorrhage, and modified Rankin Scale score at 90 days, were recorded and analyzed. Six-two patients were enrolled in this study (mean age was 60.66±13.21y, 22.6% female). The preferred angioplasty group had a higher first-pass recanalization rate than the preferred stent thrombectomy group (61.3% vs. 21.9%, P <0.001) and a higher proportion of patients who were functionally independent (defined as a modified Rankin Scale score of 0 to 3) at 90 days [odds ratio,3.681; 95% confidence interval (CI):1.009 to 13.428; P =0.048]. There was no significant difference between the groups in the time from puncture to recanalization, the frequency of successful reperfusion, and early neurological improvement, or intracranial hemorrhage ( P >0.05). This study suggests that for acute middle cerebral artery occlusion in ICAS, preferred angioplasty may be a safe and effective procedure.

Resting-State Functional Magnetic Resonance Imaging Reveals the Effects of rTMS on Neural Activity and Brain Connectivity After Experimental Stroke.

Limited understanding of neurobiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) prevents us from choosing optimal therapeutic regimen for patients to improve therapeutic efficiency. Resting-state functional magnetic resonance imaging (rs-fMRI) has been demonstrated to obtain comparable functional readouts across species. Intermittent and continuous theta burst stimulation were used to stimulate ipsilesional and contralesional hemisphere, respectively, during the subacute phase after stroke. We used a rat middle cerebral artery occlusion stroke model. The amplitude of low-frequency fluctuations and functional connectivity analyses of rs-fMRI were chosen to detect neuron activity and functional connectivity. The expression of neuron activation marker c-Fos and axonal plasticity marker GAP43 was examined by an immunochemistry method to corroborate the results of rs-fMRI. iTBS altered the long-term neuronal activity in bilateral sensorimotor cortex, whereas cTBS influenced immediate neuronal activity of bilateral sensorimotor cortex. In addition, cTBS enhanced interhemispheric and intrahemisheric functional connectivity in contralesional hemisphere, accompanied by axonal and dendritic remodeling in the perilesional cortical areas and contralesional homologous areas after large stroke. rTMS exerted complex effects on brain structural and functional connectivity in addition to affecting cortical excitability. cTBS promoted the compensatory effect of contralesional hemisphere after stroke with large lesions.

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke.

The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model. In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS. First, its effect on acute inflammation was evaluated by the mice model of increased peritoneal capillary permeability. Then, the MCAO cerebral edema models were built to evaluate its neuroprotection by reducing the neurological score, cerebral edema, improving the biochemical indicators, and pathological damage of brain tissue. At the same time, its protection on blood-brain barrier (BBB) integrity was proved by decreasing the BBB permeability and inhibiting glycocalyx degradation and regulating the BBB tight junction proteins expression of matrix metalloproteinase- 9 (MMP- 9) and claudin- 5 in brain tissue. Meanwhile, pharmacokinetic experiments showed that the compound had good BBB penetration. It has some advantages in the intensity of efficacy compared with the marketed drug edaravone. Based on these findings, SYS18 has a strong potential to become a neuroprotectant in the future.

Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location.

The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes. We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5-18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [<50% arterial territory] or large [≥50%]). Univariable and multivariable logistic regression models were fitted. Among 285 children, the outcome at median 6.1 years was 43.5% abnormal. Controlling for infarct location, increasing age-at-stroke was associated with increasing abnormal outcome. Model 1 demonstrated that, compared with neonates, abnormal outcomes were increased in early childhood (adjusted odds ratio [aOR], 2.91 [95% CI, 1.24-7.05]) and more so in middle/late childhood (aOR, 4.46 [95% CI, 1.71-12.13]). Outcomes were worse for combined locations, including anterior+posterior (model 1: aOR, 15.4 [95% CI, 4.49-64.63]) and cortical+subcortical (model 2: aOR, 10.7 [95% CI, 3.88-32.74]). Abnormal outcomes were also increased for anterior circulation (model 1: aOR, 14.91 [95% CI, 5.29-54.21]) and subcortical locations (model 2: aOR, 4.36 [95% CI, 1.37-14.95]). Among individual arterial territories, outcomes were best for superior division middle cerebral artery (100% normal) and worst for lateral lenticulostriate artery infarcts (47.4% abnormal; model 3: aOR, 14.2 [95% CI, 3.5-67.6]). Among survivors of pediatric stroke, abnormal long-term neurological outcome is increased with increasing age-at-stroke, supporting enhanced plasticity after focal injury to the newborn brain compared with older pediatric ages.

Rational development of fingolimod nano-embedded microparticles as nose-to-brain neuroprotective therapy for ischemic stroke.

Ischemic stroke is one of the major diseases causing varying degrees of dysfunction and disability worldwide. The current management of ischemic stroke poses significant challenges due to short therapeutic windows and limited efficacy, highlighting the pressing need for novel neuroprotective treatment strategies. Previous studies have shown that fingolimod (FIN) is a promising neuroprotective drug. Here, we report the rational development of FIN nano-embedded nasal powders using full factorial design experiments, aiming to provide rapid neuroprotection after ischemic stroke. Flash nanoprecipitation was employed to produce FIN nanosuspensions with the aid of polyvinylpyrrolidone and cholesterol as stabilizers. The optimized nanosuspension (particle size = 134.0 ± 0.6nm, PDI = 0.179 ± 0.021, physical stability = 72 ± 0h, and encapsulation efficiency of FIN = 90.67 ± 0.08%) was subsequently spray-dried into a dry powder, which exhibited excellent redispersibility (RdI = 1.09 ± 0.04) and satisfactory drug deposition in the olfactory region using a customized 3D-printed nasal cast (45.4%) and an Alberta Idealized Nasal Inlet model (8.6%) at 15L/min. The safety of the optimized FIN nano-embedded dry powder was confirmed in cytotoxicity studies with nasal (RPMI 2650 and Calu-3 cells) and brain related cells (SH-SY5Y and PC 12 cells), while the neuroprotective effects were demonstrated by observed behavioral improvements and reduced cerebral infarct size in a middle cerebral artery occlusion mouse stroke model. The neuroprotective effect was further evidenced by increased expression of anti-apoptotic protein BCL-2 and decreased expression of pro-apoptotic proteins CC3 and BAX in brain peri-infarct tissues. Our findings highlight the potential of nasal delivery of FIN nano-embedded dry powder as a rapid neuroprotective treatment strategy for acute ischemic stroke.

Scalp acupuncture alleviates remote hippocampal damage in MCAO rats by inhibiting neuroinflammation: A TMT-based proteomics analysis

While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO). Moreover, 74 upregulated and 50 downregulated proteins were identified in the MCAO group compared to the sham group, whilst 52 up-regulated and 50 down-regulated proteins were identified in the SA group compared to the MCAO group. Bioinformatics analysis indicated that SA may exert neuroprotective effects by modulating the acute inflammatory response and microglial activation. Additionally, SA down-regulated the expression levels of Iba-1, TNF-α, IL-1β, and IL-6, while up-regulating those of IL-4 and IL-10. Likewise, it downregulated the expression levels of three key proteins identified via proteomics analysis (Kng1, Brd9, and Magl) that may mediate the anti-inflammatory effects of SA. Overall, these results indicate that SA attenuates neuronal damage in the hippocampus and ischemic penumbra and ameliorates neurological deficits. Proteomic analysis suggested that this effect is related to the modulation of the acute inflammatory response. SA attenuated remote hippocampal damage after IS by inhibiting microglia activation and neuroinflammation. Lastly, Kng1, Brd9, and Magl were identified as potential targets that mediate the anti-inflammatory effects of SA.

Circle of Willis and Its Anatomical Relevance

The Circle of Willis is an arterial network located at the base of the brain, formed by the interconnection of the anterior, middle, and posterior cerebral arteries, along with the anterior and posterior communicating arteries. It connects the internal carotid arteries to the vertebral arteries, allowing the distribution of cerebral blood flow. Its significance lies in its ability to offer an alternative pathway in cases of arterial obstruction, helping to prevent cerebral ischemia. However, anatomical variations of this structure are common, and only 20% to 25% of the population has a "complete" or symmetrical configuration. Such variations can influence the risk of cerebrovascular diseases, such as stroke, as they may compromise the efficiency of the compensatory mechanism. These anatomical variations have a direct impact on the diagnosis and treatment of neurological conditions. The integrity of the Circle of Willis can influence the severity of symptoms in cases of ischemic strokes, as well as affect aneurysm formation and its clinical implications. Advances in imaging techniques, such as CT angiography and magnetic resonance imaging, have enabled more accurate diagnoses and the development of more effective treatments for conditions associated with the Circle of Willis, making its anatomical understanding essential for the prevention and management of cerebrovascular diseases.