Middle Cerebral Research Articles

Clipping via the Transsylvian Approach:From Basic to Advanced Surgical Techniques

The transsylvian approach is one of the most commonly used approaches in neurosurgery and is essential for clipping aneurysms located in the anterior cranial circulation, such as the middle cerebral artery, internal carotid artery, and anterior communicating artery. Moreover, basilar artery aneurysms can be clipped using this approach, albeit with some modifications. Important tips for dissecting the Sylvian fissures include reliable visualization, anatomical recognition, and steady manipulation. The actual steps are as follows: determine the affiliation of the arteries and veins, gently move the brain to create a wide space, cut the arachnoid mater, and follow the course of the arteries. In case of subarachnoid hemorrhage, irrigation and flushing out the hematoma is the key step involved in recognizing the structure and safely performing surgery. Here, we describe the basic key operative techniques for performing clipping via the transsylvian approach.

Dynamic cerebral autoregulation during repeated handgrip exercise: comparisons with spontaneous rest and sit-stand maneuvers.

Induced arterial pressure oscillation may improve the assessment of dynamic cerebral autoregulation (dCA) with transfer function analysis (TFA). This study investigated dCA during repeated handgrip exercise (RHE) compared with spontaneous rest and sit-stand maneuvers (SSM), often used in cerebrovascular research. After a 5-min rest, 20 healthy young adults (10 women and 10 men) underwent 5 min of RHE (30% maximal voluntary contraction) and SSM at 0.05 Hz and 0.10 Hz each in random order. Power spectral density (PSD) and TFA gain, phase, coherence of mean arterial pressure (MAP), and blood velocity in the middle cerebral artery (MCAvmean) were measured in very low (VLF: 0.02-0.07 Hz) and low (LF: 0.07-0.20 Hz) frequencies. End-tidal CO2 (EtCO2) was continuously recorded throughout data collection. Compared with rest, RHE increased the PSD of MAP and MCAvmean in VLF (444% and 273%, respectively) and LF (1,571% and 1,765%, respectively) (all P < 0.001). Coherence increased during RHE (VLF: 131%, LF: 128%) and SSM (VLF: 166%, LF: 136%) compared with rest (all P < 0.05). TFA gain and phase were similar between RHE and rest, but VLF gain was higher, whereas VLF and LF phases were lower during SSM than RHE (all P < 0.05). EtCO2 was higher during SSM than rest and RHE (both P < 0.05), with the individual EtCO2 changes positively correlated with VLF gain (r = 0.538, P < 0.001). These results indicate that RHE significantly increases arterial pressure oscillation and TFA coherence and may improve dCA assessment in individuals unable to perform repeated postural changes.NEW & NOTEWORTHY This is the first study investigating dynamic cerebral autoregulation (dCA) during light-intensity repeated handgrip exercise (RHE) compared with rest and sit-stand maneuvers (SSM) using transfer function analysis (TFA). Compared with rest, RHE significantly increased oscillations of arterial blood pressure and cerebral blood velocity and coherence, whereas SSM exhibited the highest oscillations and coherence. These findings suggest that RHE may serve as an alternative method for assessing dCA in individuals unable to perform repeated postural changes.

An electron paramagnetic resonance time-course study of oxidative stress in the plasma of electronic cigarette exposed rats.

The long-term consequences of electronic cigarette (Ecig) use in humans are not yet known, but it is known that Ecig aerosols contain many toxic compounds of concern. We have recently shown that Ecig exposure impairs middle cerebral artery (MCA) endothelial function and that it takes 3days for MCA reactivity to return to normal. However, the sources contributing to impairment of the endothelium were not investigated. We hypothesized that the increased levels of oxidative stress markers in the blood are correlated with impaired MCA reactivity. We used electron paramagnetic resonance (EPR) spectroscopy to examine plasma from 4-month-old male Sprague-Dawley rats that were exposed to either air (n=5) or 1h Ecig exposure, after which blood samples were collected at varying times after exposure (i.e., 1-4, 24, 48 and 72h postexposure, n=4 or 5 in each time group). The EPR analyses were performed using the redox-sensitive hydroxylamine spin probe 1-hydroxy-3-carboxymethyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) to measure the level of reactive oxidant species in the plasma samples. We found that EPR signal intensity from the CM• radical was significantly increased in plasma at 1-4, 24 and 48h (P<0.05, respectively) and returned to control (air) levels by 72h. When evaluating the EPR results with MCA reactivity, we found a significant negative correlation (Pearson's P=0.0027). These data indicate that impaired cerebrovascular reactivity resulting from vaping is associated with the oxidative stress level (measured by EPR from plasma) and indicate that a single 1h vaping session can negatively influence vascular health for up to 3 days after vaping. HIGHLIGHTS: What is the central question of this study? Does the time course of oxidative stress triggered by electronic cigarette exposure follow the cerebral vascular dysfunction? What is the main finding and its importance? Electron paramagnetic resonance analysis shows that the oxidative stress induced after a single 1h exposure to electronic cigarette aerosol takes ≤72h to return to normal, which mirrors the time course for vascular dysfunction in the middle cerebral artery that we have reported previously.

E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.

Pyroptosis has been regarded as caspase-1-mediated monocyte death that induces inflammation, showing a critical and detrimental role in the development of cerebral ischemia-reperfusion injury (IRI). MARCH1 is an E3 ubiquitin ligase that exerts potential anti-inflammatory functions. Therefore, the study probed into the significance of MARCH1 in inflammation and pyroptosis elicited by cerebral IRI. Middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice and oxygen glucose deprivation/reoxygenation (OGD/R)-treated hippocampal neurons were established to simulate cerebral IRI in vivo and in vitro. MARCH1 and PCSK9 expression was tested in MCAO/R-operated mice, and their interaction was identified by means of the cycloheximide assay and co-immunoprecipitation. The functional roles of MARCH1 and PCSK9 in cerebral IRI were subsequently determined by examining the neurological function, brain tissue changes, neuronal viability, inflammation, and pyroptosis through ectopic expression and knockdown experiments. PCSK9 expression was increased in the brain tissues of MCAO/R mice, while PCSK9 knockdown reduced brain damage and neurological deficits. Additionally, inflammation and pyroptosis were inhibited in OGD/R-exposed hippocampal neurons upon PCSK9 knockdown, accompanied by LDLR upregulation and NLRP3 inflammasome inactivation. Mechanistic experiments revealed that MARCH1 mediated ubiquitination and degradation of PCSK9, lowering PCSK9 protein expression. Furthermore, it was demonstrated that MARCH1 suppressed inflammation and pyroptosis after cerebral IRI by downregulating PCSK9 both in vivo and in vitro. Taken together, the present study demonstrate the protective effect of MARCH1 against cerebral IRI through PCSK9 downregulation, which might contribute to the discovery of new therapies for improving cerebral IRI.

Syndecan-1 as Potential Messenger of Effects of Remote Postconditioning in Experiments with Brain Ischemia

The mechanisms of cerebral reperfusion injury restriction by remote conditionig (RC) is interesting due to its possible effects on functional recovery after brain ischemia. The assessment of the role of syndecan-1 (SDC-1) and annexin-5 (ANXA5) content in blood plasma was performed by ischemic-reperfusion injury on middle cerebral artery model in rats. We used RC protocol. Randomized controlled trials were conducted. Ischemia had been done by MCAo (middle cerebral artery occlusion) by Belayev [6]. Animals used were the Wistar rat-males weighting 250 g. under general anesthesia (Zoletil 100 и Xylazine 2%). MCAo animals had been detected 41.4*±1.3 ng/ml SDC-1 plasma’s level (30%). MCAo animals with RC protocol had been detected 67.8**±5.8 ng/ml SDC-1 plasma’s level (112%). Infarction volume in MCAo animals’ brain reviled 31.97 ± 2.5% injury; the volume of infarction was 13.6 ± 1.3%. Swelling of tissue in МCАо animals with RC was 16 ± 2.1%; in contrary, in МCАо animals’ swelling of tissue was bigger up to 47 ± 3.3%. Correlation analysis in MCAo animals with RC reviled high direct correlation relationship between infarction area and muscle strength in the right forelimb (КК=0.72). Correlation analysis reviled very high inverse correlation between infarct area and capillary blood flow in МCАо animals with RC (p 0.01; r = -0.98). It is being discussed the SDC-1 protein in blood plasma may play role of potential regulator of infarct–limiting effects of remote ischemic postconditioning which cause functional recovery.

Transorbital Approach Clipping of Middle Cerebral Artery Aneurysm: A Virtual Reality Morphometric Anatomic Study

The transorbital approach (TOA) has a unique advantage to the more common lateral approaches as it provides direct access to the anterior middle fossa and medial sylvian fissure (SF) without significant dissection or retraction. However, when to use the TOA for surgical treatment of MCA aneurysms remains unclear. This study details the feasibility of clipping unruptured middle cerebral artery (MCA) aneurysms via the TOA by highlighting the anatomic features that either facilitate or hinder the approach. Virtual reality (VR) models of 25 MCA aneurysms from CT angiograms of actual patients were rendered with the relevant anatomic structures, including the neighboring temporal lobe and SF. TOA was performed on the models in VR and the globe was translated medially and inferiorly, replicating retraction used intraoperatively. Anatomic data, including the area of surgical freedom (AOF) at the aneurysm, were recorded. Trials of aneurysm clipping were conducted in VR and each aneurysm was classified as "possible" or "impossible" candidates for clipping via TOA. Separately, the relationship between surgical view and SF visualized was analyzed. Sixteen aneurysms were eliminated as candidates for TOA treatment either through VR clip trial and/or because the SF was inaccessible. The remaining 9 (36%) were candidates for TOA. Comparing the details of these two aneurysm categories with Mann Whitney U tests, there was a statistically significant difference in the AOF of the TOA approach and the width of the aneurysm dome. A clinical case report is also provided highlighting the VR rehearsal similarity with surgery. Given the minimally-invasive, technically-challenging approach, the feasibility and safety of TOA for MCA aneurysms must be evaluated before wide clinical adoption. This study identified AOF, aneurysm width, and SF accessibility as three features that may significantly impact the possibility of clipping MCA aneurysms via TOA.

Assessing the Role of Fetal Doppler in High-Risk Obstetrics: Evidence From a Comprehensive Study.

Background Colour Doppler ultrasound is pivotal in modern obstetrics for evaluating maternal and fetal health, especially in high-risk pregnancies. It enhances fetal oxygenation and nutrient delivery assessment, aiding in the early detection of adverse outcomes. However, its effectiveness is influenced by operator skill and the potential for interpretative variability. Aim This study aims to assess the utility of Doppler ultrasound in evaluating fetal status in high-risk pregnancies at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India. Materials and methods A hospital-based observational study was conducted from September 2022 to July 2024, including 145 high-risk pregnant women, of whom 120 delivered at the institute. The study included thorough maternal and fetal assessments, with regular Doppler studies starting at 28 weeks of gestation. The frequency of these studies was adjusted according to the changes and severity observed in the indices. Detailed documentation of both maternal and neonatal outcomes was meticulously maintained. Statistical analyses were performed using MS Excel (Microsoft® Corp., Redmond, WA, USA) and RStudio,Version 2023.08.0-daily+170 (RStudio, Inc., Boston, MA, USA), with a significance threshold of p < 0.05. Results The majority of participants were aged 21-30 years, with multigravida constituting 63.33%. Pregnancy-induced hypertension (PIH) and preeclampsia were the most common high-risk factors (28.33%). Abnormal umbilical artery (UA) flow patterns were observed in 58.33% of cases. Abnormal UA and middle cerebral artery (MCA) Doppler indices correlated significantly with adverse outcomes. Most deliveries were via caesarean section (82.5%), and 63.33% of neonates required Neonatal Intensive Care Unit (NICU) admission. Neonates with abnormal antenatal Doppler studies had significantly lower APGAR (appearance, pulse, grimace, activity, and respiration) scores and higher NICU admission rates. Discussion The study highlights the critical role of Doppler ultrasound in managing high-risk pregnancies, providing essential data for early interventions. Consistent with other studies, abnormal Doppler patterns were significantly associated with adverse neonatal outcomes, necessitating timely caesarean deliveries. Conclusion Fetal Doppler ultrasonography is essential for managing high-risk pregnancies, enabling timely therapeutic interventions and improving perinatal outcomes. Despite its limitations, Doppler technology remains invaluable in identifying at-risk foetuses and guiding clinical decisions for optimal pregnancy management.

High-resolution magnetic resonance imaging features of time-of-flight magnetic resonance angiography signal loss and its relevance to ischemic stroke.

Focal signal loss of intracranial artery stenosis is commonly observed on three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA). We aimed to investigate the underlying pathophysiology of vessel signal loss observed on 3D-TOF-MRA and its relevance to recent ischemic stroke. High-resolution magnetic resonance imaging (HR-MRI) was performed in 401 patients with unilateral or bilateral moderate-to-severe stenosis (50-99%) of the middle cerebral artery (MCA) on TOF-MRA. The patients were classified according to the presence or absence of focal signal loss in the M1 segment of the MCA. The wall features between the vessels with and without signal loss were compared, and their relationship with recent ischemic stroke was analyzed. A total of 414 stenotic lesions caused by atherosclerotic plaque were detected, including 231 with signal loss on TOF-MRA and 183 without. The signal loss group, compared to the group without signal loss, showed a higher degree of stenosis (P<0.001), grade 2 enhanced plaques (82.3% vs. 28.4%; P<0.001), and concentric pattern (63.2% vs. 34.4%; P<0.001). Multivariate analysis suggested grade 2 enhanced plaques and concentric pattern were independently associated with signal loss. Patients in the signal loss group were more likely to have had a recent ischemic stroke (62.4% vs. 40.4%; P<0.001). In addition to the degree of stenosis, the vulnerability and morphology of plaques on HR-MRI may influence signals on 3D-TOF-MRA. The presence of signal loss on 3D-TOF-MRA is associated with recent ischemic stroke.

Pseudo-continuous and territorial arterial spin labeling MRI for assessment of cerebral perfusion in moyamoya disease after revascularization: A comparative study with digital subtraction angiography

PurposeTo evaluate if pseudo-continuous arterial spin labeling (pcASL) and territorial ASL (tASL) can assess cerebral perfusion post-revascularization in Moyamoya disease and compare with digital subtraction angiography (DSA) outcomes. Materials and methodsPatients diagnosed with Moyamoya disease who underwent pcASL using two post-labeling delays (short ASL, 1,525 ms; delayed ASL, 2,525 ms), tASL, and DSA 3 months after surgery at a single institution were retrospectively evaluated. Manual delineation on pcASL cerebral blood flow (CBF) maps covered middle cerebral artery (MCA) territory on both sides, and cerebellum. Normalized CBF (nCBF) was calculated. Revascularization in the MCA territory was evaluated with external carotid angiography and tASL, graded on a three-point scale. Intermodality agreement was analyzed with weighted κ statistics. Correlation between pcASL-derived nCBF and tASL-measured revascularization, and revascularization grade from direct angiography, was determined. Diagnostic performance of pcASL and tASL was evaluated using DSA as a reference via receiver operating characteristic (ROC) curve analysis. ResultsA total of 32 hemispheres from 31 patients were assessed. On the operated side, sASL and dASL had nCBF values of 1.00 ± 0.30 and 1.31 ± 0.31, respectively. Revascularization area grading showed substantial intermodality agreement (weighted κ = 0.68; 95 % CI: 0.49, 0.87). DSA revascularization moderately correlated with sASL and dASL nCBF values (r = 0.56 and 0.47) and strongly correlated with tASL revascularization area (r = 0.73). ROC analysis revealed that sASL and dASL nCBF values reflected revascularization (area under the curve (AUC) = 0.86 and 0.77) and tASL revascularization area (AUC = 0.91). Combined pcASL and tASL had an AUC of 0.93, comparable to tASL alone, improving diagnostic performance. The diagnostic accuracy of nCBF for sASL was 87.5 %, superior to 75 % for dASL. The diagnostic accuracy of tASL external carotid artery revascularization area was 87.5 %, with sensitivity and specificity of 88 % and 85.7 %, respectively. ConclusionThe combination of pcASL and tASL outperformed pcASL alone in assessing cerebral perfusion post-Moyamoya disease revascularization.

Maternal use of electronic cigarettes and impact on offspring: a double-hit model.

Endothelial dysfunction is a predictor for cardiovascular disease. Preclinical data suggest longstanding cardiovascular and cerebrovascular dysfunction occurs in offspring with perinatal electronic cigarette (Ecig) exposure. Furthermore, direct use of Ecigs increases reactive oxygen species and impairs cerebrovascular function, but the combined effect of direct use in offspring with a history of perinatal exposure (i.e. double-hit condition) is not known. We tested the hypothesis that offspring with double-hit Ecig exposure will lead to greater cerebrovascular and neurocognitive dysfunction compared with in utero exposure only. Male and female offspring were obtained from time-mated Sprague Dawley female rats exposed to air (n = 5 dams) or Ecig exposed (n = 5 dams) and studied at either 3 or 6 mo after birth. Ecig exposure for double-hit offspring began at 1-mo before the timepoints and lasted 4 wk (5 days/wk with 90-min exposure/day). We found double-hit offspring (Ecig:Ecig = exposure dam:offspring) sustained further blunted middle cerebral artery (MCA) reactivity, increased severity of neuronal damage, and increased interactions of astrocytes and endothelial cells compared with offspring with maternal (Ecig:Air) or direct (Air:Ecig) exposure only. Circulating extracellular vesicles (EVs) were increased, whereas sirtuin 1 (SIRT1) was decreased, in all Ecig-exposed groups compared with controls (Air:Air), with Ecig:Ecig group showing the greatest respective change for each. Electron paramagnetic resonance (EPR) spectroscopy revealed oxidative stress was the highest in the plasma of Ecig:Ecig group (P < 0.05) than the other groups. These data show that a double-hit exposure in adolescent or adult offspring results in a greater decline in cerebrovascular function, biomarkers of neuronal dysfunction, and increased circulation of EVs compared with a single-hit exposure.NEW & NOTEWORTHY These data add to the growing body of literature demonstrating that electronic cigarette (Ecig) use during pregnancy (even without nicotine) is not safe, and primes offspring to have worse cardiovascular health outcomes in early and adult life. A key finding from this work is that a second insult from direct vaping in offspring with prior in utero exposure induces greater vascular dysfunction, increased oxidative stress, and shows evidence of neuronal dysfunction compared with either direct- or maternal-only exposure.

Early Surgical Intervention In Large Mca Infarction: Meta-Analysis Report

Objective: To assess the effectiveness and safety of early surgical intervention, specifically decompressive craniectomy (DC), in patients with large middle cerebral artery (MCA) infarction. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing early surgical intervention with medical management. Results: Early surgical intervention demonstrated a significant reduction in mortality and improved functional outcomes, particularly in younger patients. However, it was associated with increased complication rates. Conclusion: Early surgical intervention can benefit select patients with large MCA infarctions, but careful patient selection is essential.

Characterizing Revascularization After Encephalo-Duro-Arterio-Synangiosis (EDAS) in Adult Patients With Moyamoya Disease Using the Orbital Grading System

The Matsushima Grade has traditionally been used to evaluate vessel ingrowth from the STA after EDAS for MMD-patients. However, this grading is subjective and prone to measurement variability. Herein, we propose the orbital grading system quantifying leptomeningeal and burr hole-related vessel-ingrowth from the STA and/or MMA to the middle and anterior cerebral arteries post-EDAS in MMD patients. An anatomical classification was developed by reference to two parallel vertical lines from the bony landmarks of the orbit, categorized from Grade 0-3. Regression models were used to compare clinical and functional outcomes of our grading system with the Matsushima scale. Forty MMD patients, with median age of 48 years, mostly females (72.5%), were included. Presentation included ischemic events (65.0%), hemorrhage (22.5%), and seizures (7.5%). Most patients were categorized as Suzuki ≥ IV (69.5%). Fifty EDAS (89.9%) had concurrent burr holes placed (parietal and frontal regions). At a median follow-up of 13.7 months, collateral growth was graded as follows: grade 0 (6;10.8%), grade 1 (12;21.4%), grade 2 (23;41.1%) and grade 3 (15;26.8%). Linear regression showed similarities in the distribution between the orbital grading system and Matsushima grading (r=0.86;p<0.01). Ischemic events were fewer in hemispheres categorized as grade 2-3 compared to grade 0-1 (p=0.047) as well as in Matsushima grading A or B compared to C (p=0.047). The orbital grading system demonstrated agreement in identifying postoperative ischemic events as the Matsushima grade and provides a more practical and objective evaluation of collateral vessel ingrowth after EDAS with and without burr-holes.

The effect of posture on the age dependence of neurovascular coupling.

Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

Effects of thrombus characteristics on clinical outcome and success of recanalization in acute ischemic stroke

Background: Despite current developments in mechanical thrombectomy (MT), successful recanalization cannot be achieved in all patients. One of the factors related to this is the characteristics of the thrombus. In this study, we aimed to evaluate the effects of thrombus length and permeability on procedural success and clinical outcome. Methods: Patients with intracranial ICA, middle cerebral artery M1, or M2 occlusions, who underwent MT between November 2019 and January 2022 were included in the study. Thrombus length, density and permeability were calculated and the relationship between recanalization success and modified Rankin Scores (mRS) at the 3rd month was evaluated. Good clinical outcome was defined as an mRS score of 2 or less. Results: Forty-six of the 79 patients included in the study had a good clinical outcome. Although thrombus length was shorter and permeability was higher in patients with good clinical outcome, statistical significance was not achieved. There was a positive correlation between thrombus density, thrombus length and the number of passes, and a negative correlation between permeability. There was no significant difference in thrombus length, density and permeability between patients with and without successful recanalisation. Thrombus length was found to be a predictor of clinical outcome at 3 months in univariate analysis, whereas only age was found to be an independent predictor in multivariate analysis. Conclusions: In conclusion, despite certain findings not achieving statistical significance, the observed trends offer valuable insights for future research. A comprehensive understanding of thrombus nature could guide personalized stroke treatment strategies in the future.

HIF-1α knockdown attenuates inflammation and oxidative stress in ischemic stroke male rats via CXCR4/NF-κB pathway.

Hypoxia inducible factor-1α (HIF-1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF-1α on ischemic stroke (IS). IS model was established using middle cerebral artery occlusion (MCAO)-modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated mice hippocampal cells HT22, followed by the silencing of HIF-1α and the overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor-kappa B (NF-κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. The levels of tumor necrosis factor-α, Interleukin (IL)-6, IL-1β, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R-modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2'-7'dichlorofluorescin diacetate (DCFH-DA) probe. The levels of HIF-1α, CXCR4, and NF-κB p65 were quantified via Western blot and immunofluorescence, respectively. HIF-1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF-κB p65 in MCAO-modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF-κB. Also, in OGD/R-treated HT22 cells, HIF-1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF-κB p65, while promoting viability. However, CXCR4/NF-κB p65 overexpression did the opposite. HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

Detection of lipid radicals generated via cerebral ischemia/reperfusion injury using a radiolabeled nitroxide probe

Reactive oxygen species generated via reperfusion cause lipid damage and induce lipid peroxidation, leading to cerebral ischemia/reperfusion injury and exacerbation of cerebral infarction. Lipid radicals are key molecules generated during lipid peroxidation. Therefore, understanding the spatiotemporal behavior of lipid radicals is important to improve the therapeutic outcomes of cerebral infarction. However, the behaviors of lipid radicals in the brain remain unclear. In this study, we aimed to evaluate the distribution of radioactivity in a transient middle cerebral artery occlusion (tMCAO) model using lipid radical detection probe [125I]1 to assess the behaviors of lipid radicals after cerebral ischemia/reperfusion. The tMCAO model administered [125I]1 exhibited significant differences in the timing and location of radioactivity accumulation between the ischemic and non-ischemic regions. Liquid chromatography/mass spectrometry analysis identified the lipid radical adducts formed by the reaction of 1 with the lipid radicals generated after reperfusion. More adducts were detected in the ischemic region samples than in the non-ischemic region samples. Therefore, 1 successfully detected the lipid radicals generated after cerebral ischemia/reperfusion. Overall, this study demonstrates the potential of nuclear medical imaging using radiolabeled 1 to detect the lipid radicals generated after cerebral ischemia/reperfusion. Our approach can aid in the development of new therapeutic agents scavenging lipid radicals after cerebral reperfusion by facilitating the determination of therapeutic efficacy and optimal administration period.

Myrtenol-Loaded Fatty Acid Nanocarriers Protect Rat Brains Against Ischemia-Reperfusion Injury: Antioxidant and Anti-Inflammatory Effects.

This research investigated the preventive effects of myrtenol (MYR), fatty acid nanocarriers (FANC), and myrtenol-loaded FANC (MYR + FANC) on neurological disturbance, stroke volume, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-α) in the brain with ischemia-reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in rats. Seventy two Wistar male rats were divided into six main groups. The groups were sham, ischemia-reperfusion group (MACO), MACO-MYR (50 mg/kg), MACO-FANC (50 and 100 mg/kg), and MACO-MYR + FANC (50 mg/kg). Stroke volume, neurological deficit scores, and the brain levels of MDA, SOD, and TNF-α were examined with TTC staining, observation, and ELISA, respectively. Pretreatment with MYR, FANC (100 mg/kg), and MYR + FANC reduced the neurological deficit score and cerebral infarction volume. MYR, FANC (100 mg/kg), and MYR + FANC pretreatment increased and decreased brain SOD and MDA levels compared to MACO group, respectively. The TNF-α level decreased in the MYR + FANC group compared to MCAO and MCAO-MYR groups in the brain. The use of FANC (100 mg/kg), MYR, and MYR + FANC has protective effects against oxidative stress and ischemia-reperfusion injury. FANC probably improve the bioavailability of MYR, as MYR+ FANC had more therapeutic effects on the reduction of ischemia-reperfusion injuries, inflammation, and oxidative stress.

The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion.

The analysis of alterations in the expression and functionality of brain-derived exosomal miRNAs within ischemic stroke lesions provides significant insights into the mechanisms that contribute to disease recovery. We assessed spontaneous motor function in a rat model of permanent middle cerebral artery occlusion (pMCAO) using motor function scores and magnetic resonance imaging (MRI). Brain-derived exosomes from the infarcted brain tissue of the animal model were extracted and high-throughput sequencing of them was performed followed by bioinformatics analysis for differentially expressed miRNAs target genes. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure expression levels of differentially expressed miRNAs at various time points. The oxygen-glucose deprivation (OGD) model was established to investigate gene function through the assessment of cell proliferation and apoptosis using EdU proliferation and JC-1 apoptosis assay. The rat model demonstrated a spontaneous recovery of motor function and a reduction in cerebral infarction area from day 1 to day 14 post-operation. Over the course of the recovery period, miR-24-3p, miR-129-1-3p, and miR-212-5p maintained consistent expression levels, reaching their peak on the initial day following surgery. In the cell model, EdU detection indicated that miR-129-1-3p promoted cellular proliferation, while JC-1 detection revealed its suppressive impact on cellular apoptosis. The current research findings indicated the presence of spontaneous motor function restoration in a rat model of ischemic stroke. MiR-24-3p, miR-129-1-3p, and miR-212-5p were identified as pivotal genes in this recovery process, with miR-129-1-3p potentially influencing the restoration of spontaneous motor function in ischemic stroke through the regulation of neuronal proliferation and apoptosis.

Inhibition of sodium-glucose cotransporter-2 improves anaemia in mice and humans with sickle cell disease, and reduces infarct size in a murine stroke model.

Sodium-glucose cotransporter-2 (SGLT-2) is expressed in the kidney and may contribute to anaemia and cardiovascular diseases. The effect of SGLT-2 inhibition on anaemia and vascular endpoints in sickle cell disease (SCD) is unknown. A murine model of SCD was studied to determine the effects of the SGLT-2 inhibitor, empagliflozin, on anaemia and stroke size. The University of Michigan's Precision Health Database was used to evaluate the effect of SGLT-2 inhibitors on anaemia in humans with SCD. SCD mice treated with daily empagliflozin for 8 weeks demonstrated increases in haemoglobin, haematocrit, erythrocyte counts, reticulocyte percentage and erythropoietin compared to vehicle-treated mice. Following photochemical-induced thrombosis of the middle cerebral artery, mice treated with empagliflozin demonstrated reduced stroke size compared to vehicle treated mice. In the electronic health records analysis, haemoglobin, haematocrit and erythrocyte counts increased in human SCD subjects treated with an SGLT-2 inhibitor. SGLT-2 inhibitor treatment of humans and mice with SCD is associated with improvement in anaemic parameters. Empagliflozin treatment is also associated with reduced stroke size in SCD mice suggesting SGLT-2 inhibitor treatment may be beneficial with regard to both anaemia and vascular complications in SCD patients.

Potential of BMI as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

To investigate the association between BMI and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. The authors analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, the authors compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to 2 years-among patients with varying BMIs who underwent either surgery or medical treatment. Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within 2 years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m 2 ; 95% CI: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5kg/m 2 . Patients with BMI ≥24.5kg/m 2 experienced a higher incidence of IIS compared to those with BMI <24.5kg/m 2 (17.4 vs. 0.0%, P <0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5kg/m 2 (5.3 vs. 19.8%, P <0.01) and those with BMI <24.5kg/m 2 (10.6 vs. 1.4%; P =0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5kg/m 2 . Data from the CMOSS trial indicate that patients with BMI ≥24.5kg/m 2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.