Middle Cerebral Research Articles

Melastoma dodecandrum lour. Protects against cerebral ischemia–reperfusion injury by ameliorating oxidative stress and endoplasmic reticulum stress

Ethnopharmacological relevanceMelastoma dodecandrum Lour. (MD), a traditional Chinese medicine used by the She ethnic group, has been used to treat cerebral ischemia-reperfusion (CIR) injury due to its efficacy in promoting blood circulation and removing blood stasiss; however, the therapeutic effects and mechanisms of MD in treating CIR injury remain unclear. AimTo investigate the protective effects of MD on CIR injury, in addition to its impact on oxidative stress, endoplasmic reticulum (ER) stress, and cell apoptosis. Materials and methodsThe research was conducted using both cell experiments and animal experiments. The CCK-8 method, immunofluorescence staining, and flow cytometry were used to analyze the effects of MD-containing serum on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cell viability, reactive oxygen species (ROS) clearance, anti-inflammatory, neuroprotection and inhibition of apoptosis. Furthermore, 2,3,5-Triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, Nissl staining, and immunohistochemistry were used to detect infarct size, pathological changes, Nissl corpuscula and neuronal protein expression in middle cerebral artery occlusion (MCAO) rats. Polymerase chain reaction and Western Blotting were conducted in cell and animal experiments to detect the expression levels of ER stress-related genes and proteins. ResultsThe MD extract enhanced the viability of PC12 cells under OGD/R modeling, reduced ROS and IL-6 levels, increased MBP levels, and inhibited cell apoptosis. Furthermore, MD improved the infarct area in MCAO rats, increased the number of Nissl bodies, and regulated neuronal protein levels including Microtubule-Associated Protein 2 (MAP-2), Myelin Basic Protein (MBP), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament 200 (NF200). Additionally, MD could regulate the expression levels of oxidative stress proteins malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT). Both cell and animal experiments demonstrated that MD could inhibit ER stress-related proteins (GRP78, ATF4, ATF6, CHOP) and reduce cell apoptosis. ConclusionThis study confirmed that the therapeutic mechanism of the MD extract on CIR injury was via the inhibition of oxidative stress and the ER stress pathway, in addition to the inhibition of apoptosis.

Involvement of Subinsular Territory Stroke as Predictor of Outcome after Successful Endovascular Recanalization of Left Middle Cerebral Artery Occlusion.

Subinsular stroke (subIS) can occur between the penetrating middle cerebral artery (MCA) branches, which clinical and radiological findings sometimes encounter in patients after the recanalization of left proximal MCA occlusion. However, no supportive data are available to clarify this relationship. This study investigated whether the involvement of subIS can impact outcomes after successful reperfusion therapy. Data from 152 consecutive patients who underwent endovascular thrombectomy between 2019 and 2023 were collected. A 3-month functional independence defined as a modified Rankin Scale 0-2 (primary outcome) and influencing factors were analyzed retrospectively. Recanalization was achieved in 35 patients, of whom 11 (31%) developed subIS. Patients with subIS were older in age (81 vs. 75; p < 0.05), had lower apparent diffusion coefficient (ADC) values on admission (0.52 vs. 0.62; p < 0.001), and higher modified Rankin Scale (mRS) scores (4 vs. 2; p < 0.001) than those without subIS. In a multivariate analysis, subIS was independently associated with a worse functional outcome (odds ratio: 10.5, p = 0.02). The cut-off value of the ADCs was 0.52 with a sensitivity and specificity of 70% and 64%, respectively. Subinsular ischemic lesions contribute to poor functional independence in patients after the successful recanalization of left MCA occlusion. The attenuation of the ADC value in these territories could be a valuable predictor of the outcome.

Efficacy of Dry Needling in Enhancing Hand Function and Reducing Spasticity in MCA Stroke Patients: A Prospective Case Report

Stroke, particularly involving the middle cerebral artery (MCA), often leads to persistent disability, significantly impairing hand function and inducing severe spasticity in the forearm flexors due to complex motor pathway involvement. This case report evaluates the effectiveness of combining dry needling therapy (DNT) with task-oriented training (TOT) in reducing spasticity and improving hand function in a post-MCA stroke patient. A 61-year-old male with right-side hemiplegia following a left MCA stroke, compounded by a history of diabetes, hypertension, and recent kidney stone diagnosis, participated in this study. The patient experienced severe functional limitations due to spasticity (grade 3 on the Modified Ashworth Scale) and scored 31 on the CAHAI-13, indicating significant hand dysfunction. DNT was applied to key forearm muscles (flexor carpi radialis, flexor carpi ulnaris, flexor digitorum superficialis, flexor digitorum profundus, and pronator teres), followed by TOT targeting daily tasks. Post-intervention, the patient demonstrated significant improvements: spasticity was reduced (Modified Ashworth Scale score decreased from grade 3 to grade 2), and muscle hypertonicity, as measured by EMG, was reduced in all targeted muscles. Functional hand use improved markedly, with the CAHAI-13 score increasing from 31 to 45. These improvements led to enhanced independence in daily activities. This case report highlights the clinical relevance of integrating DNT with TOT in stroke rehabilitation. The combined intervention not only reduced spasticity and improved neuromuscular function but also led to meaningful gains in hand function, enhancing the patient’s ability to perform daily activities independently. Given the promising results, this combined approach could serve as a practical and effective strategy for improving motor recovery and functional independence in post-stroke patients. Further studies with larger sample sizes are necessary to confirm these findings and explore the broader application of this approach in clinical practice.

Apolipoprotein E deficiency exacerbates blood-brain barrier disruption and hyperglycemia-associated hemorrhagic transformation after ischemic stroke

BackgroundThe polymorphism of the apolipoprotein E (ApoE) gene has been implicated in both the susceptibility to neurodegenerative disease and the prognosis of traumatic brain injury (TBI). However, the influence of ApoE on the risk of hemorrhagic transformation (HT) after acute ischemic stroke remains inconclusive. The present study aimed to investigate the potential impact of ApoE deficiency on the risk of hyperglycemia-associated HT and to elucidate the underlying mechanisms. MethodsWild-type (WT) and ApoE knockout (ApoE−/−) mice were injected with 50 % glucose to induce hyperglycemia and subsequently subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO). The mortality, neurological function, HT incidence and HT grading-score were evaluated at 24 hours after reperfusion. To evaluate the integrity of blood-brain barrier (BBB), the immunoglobulin G (IgG) leakage and the protein expressions of tight junctions (TJs) were detected using immunofluorescent staining and western blotting. Finally, the levels of matrix metalloproteinases (MMP)-2/9, microglial activation and proinflammatory mediators were investigated using immunofluorescent staining and western blotting. ResultsApoE−/− mice exhibited increased mortality and exacerbated neurological impairment, concomitant with more severe hyperglycemia-associated HT 24 hours post-reperfusion. Meanwhile, ApoE deficiency exacerbated the disruption of BBB, characterized by increased leakage of IgG, aggravated degradation of TJs and microvascular basement membranes. Furthermore, ApoE deficiency further aggravated the upregulation of MMP-2/9 and microglia-triggered neuroinflammation. ConclusionsOur findings demonstrate that the absence of ApoE exacerbates neurological impairment and hyperglycemia-associated HT in ischemic stroke mice, which is closely associated with MMP-2/9 signaling and neuroinflammation-mediated disruption of BBB.

Neuroprotection on ischemic brain injury by Mg2+/H2 released from endovascular Mg implant

Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg2+/H2 from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. In vitro analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg2+/H2 delivery system for treating distant cerebral ischemic diseases.

Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein β to ameliorate cerebral ischaemia/reperfusion injury.

This study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto-oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C-EBPβ in the hippocampus following I/R. Key to the study is understanding how Jun controls C-EBPβ degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein-protein interaction (PPI) in mouse models have indicated involvement of Jun (AP-1) in I/R-induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen-glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C-EBPβ degradation, thereby diminishing cerebral I/R injury through the SOCS1/C-EBPβ pathway. These insights provide a deeper understanding of post-I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. KEY POINTS: Jun and SOCS1 are poorly expressed, and C-EBPβ is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination-dependent C-EBPβ protein degradation. Jun blunts oxygen-glucose deprivation/reoxygenation-induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post-I/R brain injury.

Focused magnetic stimulation for motor recovery after stroke

Background and objectivesThe effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. MethodsWe randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. ResultsThe Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1β, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. ConclusionsFocused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation

BackgroundStroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke.MethodsWe administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion–reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model.ResultsWe found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1β levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1β release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy.ConclusionThe HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

Post-stroke whole body vibration therapy alters the cerebral transcriptome to promote ischemic tolerance in middle-aged female rats

Low-frequency whole body vibration (WBV; 40 Hz) therapy after stroke reduces ischemic brain damage, motor, and cognitive deficits in middle-aged rats of both sexes. However, the underlying mechanisms responsible for WBV induced ischemic protections remain elusive. In the current study, we hypothesize that post-stroke WBV initiates transcriptional reprogramming in the cortex of middle-aged female rats which is responsible for the observed reduced stroke consequences. Middle-aged female Sprague-Dawley rats that remained in constant diestrus (reproductively senescent) were randomized to either sham or transient middle cerebral artery occlusion (tMCAO; 90 min) surgery. A day after induction of tMCAO, animals received either WBV or no-WBV treatment for 15 min twice a day for five days for a week. Post-treatment, cortical tissue was analyzed for gene expression using RNA sequencing (RNAseq) and gene enrichment analysis via Enrichr. The RNAseq data analysis revealed significant changes in gene expression due to WBV therapy and the differentially expressed genes are involved in variety of biological processes like neurogenesis, angiogenesis, excitotoxicity, and cell death. Specifically, observed significant up-regulation of 116 and down-regulation of 258 genes after WBV in tMCAO exposed rats as compared to the no-WBV group. The observed transcriptional reprogramming will identify the possible mechanism(s) responsible for post-stroke WBV conferred ischemic protection and future studies will be needed to confirm the role of the genes identified in the current study.

Sufentanil-induced Nrf2 protein ameliorates cerebral ischemia-reperfusion injury through suppressing neural ferroptosis

As an oxidative stress and inflammation-related disease, cerebral ischemia-reperfusion injury (CIRI) is a prevalent pathogenic factor of ischemic stroke (IS) and seriously degrades the life quality of human beings. As an opioid analgesic for anesthesia, Sufentanil (SUF) can activate the Nrf2 protein-induced anti-oxidant effects, which indicate that SUF may be used as alternative drug for CIRI therapy, but little is known regarding to its molecular mechanisms. Thus, this research aimed to examine whether SUF pre-treatment alleviated CIRI through the modulation of Nrf2 protein-mediated antioxidant activity. Our research revealed that middle cerebral artery occlusion/reperfusion (MCAO/R)-treated rats exhibited apparent CIRI-related symptoms and induced damages in rats' brain, which were all notably mitigated in the MCAO/R rats. The subsequent in vitro cellular experiments verified that oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cytotoxicity were apparently reversed by SUF co-treatment in HT22 and BV2 cells, and it was also validated that SUF was capable of suppressing inflammation and ferroptosis in CIRI models by inhibiting oxidative stress-related damages. Mechanistically, the Akt/GSK-3β pathway was excessively activated by SUF to promote Nrf2 protein expressions and enhance Nrf2-meidated anti-oxidant effects, and it was found that SUF-induced protective effects during CIRI progression were all abrogated by co-treating cells with MK2206 (Akt inhibitor), NP-12 (GSK-3β inhibitor), or ML385 (Nrf2 inhibitor). In conclusion, SUF activated the Akt/GSK-3β pathway to initiate Nrf2 protein-mediated antioxidant effects, which further suppressed oxidative stress-related inflammation and ferroptosis to ameliorate CIRI progression, and SUF could potentially be used as novel therapeutic agent for CIRI treatment in clinic.

Combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter for M2 occlusions: the ONE-SEG technique.

Endovascular therapy (EVT) for distal medium vessel occlusions requires prioritizing effectiveness and safety. We developed a technique combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter (AC) for M2 occlusions, called the "ONE-SEG technique," and evaluated its clinical and technical impacts. This was a retrospective review of 30 consecutive patients with M2 segment middle cerebral artery occlusion treated using the ONE-SEG technique. This method involves deploying the EMBOTRAP III through a microcatheter in only one segment and guiding the AC to the M2 origin or distal M1. The rates of final-pass expanded thrombolysis in cerebral infarction (eTICI) scores of 2c/3 or 2b/2c/3, safety (symptomatic intracranial hemorrhage [sICH]), and clinical outcomes (modified Rankin Scale [mRS] score 0-2, 0-3 at 90 days, and mortality at 90 days) were evaluated. Of the 30 cases, 36.7% were female, and the mean age was 75.6 ± 11.0 years. The ONE-SEG technique was used for 17 cases (56.7%, median NIHSS 10 [5-15.5]) with primary M2 occlusion and 13 cases (43.3%, median NIHSS 20 [14-22.5]) with secondary M2 occlusion after proximal thrombus removal. The successful final reperfusion rate (eTICI 2b/2c/3) was 90% overall (27/30 cases). One case (3.3%) developed sICH with secondary M2 occlusion. At 3 months, mRS scores 0-2 were seen in 64.7% of patients with primary M2 occlusion (11/17 cases) and in 23.1% (3/13 cases) with secondary M2 occlusion. EVT using the ONE-SEG technique appears to be safe and effective for M2 occlusion.

RNF213 Mutation Associated with the Progression from Middle Cerebral Artery Steno-Occlusive Disease to Moyamoya Disease.

Middle cerebral artery steno-occlusive disease (MCAD) has been recognized as a different clinical entity from moyamoya disease (MMD). Although MCAD can progress to MMD, the extent to which patients actually progress and the risk factors for this progression have not been fully elucidated. We retrospectively reviewed patients with MCAD who underwent RNF213 genotyping. Demographic features, RNF213 p.R4810K mutation, medical history, and longitudinal changes in angiography were analyzed. Sixty patients with 81 affected hemispheres were enrolled. During the follow-up period, 17 patients developed MMD, and the RNF213 p.R4810K mutation was the only factor significantly associated with progression to MMD (odds ratio, 16.1; 95% CI, 2.13-731; P = 0.001). The log-rank test demonstrated that patients with the mutation had a higher risk of progression to MMD (P = 0.007), stenosis progression (P = 0.010), and symptomatic cerebral infarction or hemorrhage (P = 0.026). In Cox regression analysis the p.R4810K mutation remained a significant factor after adjusting for age group (childhood or adult onset) at diagnosis (hazard ratio, 8.42; 95% CI, 1.10-64.4). Hemisphere-based analysis also showed that the mutation was associated with a higher risk of progression to the MMD hemisphere (P = 0.002), stenosis progression (P = 0.005), and cerebral infarction or hemorrhage (P = 0.012). The RNF213 p.R4810K mutation was identified as a risk factor for progression from MCAD to MMD. Genotyping for this mutation may contribute to risk stratification in MCAD.

Adenosine-induced cardiac standstill in intracranial aneurysm surgery: A case report

Surgical clipping of complex intracranial aneurysms can pose intraoperative challenges due to difficulty in anatomic exposure and uncontrolled intraoperative rupture, leading to significant morbidities or mortalities. This report presents a case of a 61-year-old Asian male with an unruptured saccular basilar tip aneurysm and an unruptured right middle cerebral artery aneurysm. The patient underwent a left temporal craniotomy and clipping of an unruptured basilar tip aneurysm, successfully achieved through adenosine-induced cardiac standstill. This technique reduces perfusion pressure and decreases the turgor of the aneurysm, thereby facilitating clip ligation. Our experience demonstrated that thorough, careful patient selection, optimal anesthetic management, and proper communication between neurosurgeon and anesthesiologist are important for achieving successful surgical outcomes.

Exogenous leptin alleviates glutamate-excitotoxic injury caused by cerebral ischemia–reperfusion in mice by affecting the expression of glutamate transporters

Ischemic stroke is characterized by high morbidity and mortality and a lack of effective therapeutic interventions. Leptin plays an important role in regulating oxidative stress, angiogenesis, hematopoiesis, etc. Although recent studies have found a neuroprotective effect of leptin, little is known about its role in cerebral ischemia. This study explores the possible roles and potential preventative mechanisms of leptin in cerebral ischemia–reperfusion injury (CIRI). An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to replicate the CIRI model, low (0.5 mg/kg), medium (1 mg/kg) and high (2 mg/kg) concentrations of leptin were injected intraperitoneally immediately after inserting the embolic line. After 1.5 h of ischemia and 24 h of reperfusion, we examined the neural function of the mice, collected brain tissue for histological examination, and screened for the optimal concentrations of leptin intervention. On this basis, we observed the changes of cortical apoptosis injury, intracellular calcium fluorescence intensity and astrocyte glial fibrillary acidic protein (GFAP) expression and morphological changes. In addition, we also tested the expression of transporters and metabolism-related enzymes (VGLUT-1, VGLUT-2, GLAST, GLT-1, GS, ATP1α1), the expression of inflammatory factors and the content of glutamate (Glu). Compared with the I/R group, we found that leptin improved neurological deficits, reduced the area of infarcts, maintained the normal morphology of astrocytes (AST), downregulated the expression of VGLUT-1, and upregulates the expression of GLT-1 and GLAST, thereby reducing the content of Glu in the synaptic cleft. Our studies suggest that leptin may have a neuroprotective effect by decreasing the excitotoxicity of glutamate.

Electroacupuncture promotes angiogenesis by regulating miR-142-5p and activating ADAMTS1/PI3K/AKT pathway in ischemic stroke rats.

To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke. This study was divided into two parts. The first part of the experiment：SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively；HE staining was used to observe the cortical pathological changes；immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment：The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot. In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased (P<0.01)；the volume of cerebral infarction in the model group was significantly increased (P<0.01)；the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased；the cerebral microvascular density was significantly increased (P<0.01)；the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased (P<0.01, P<0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated (P<0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated (P<0.01, P<0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased (P<0.01), the volume of cerebral infarction was significantly decreased (P<0.01)；the degree of brain edema and neuronal necrosis were alleviated；the cerebral microvascular density was significantly increased (P<0.01)；the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased (P<0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased (P<0.01, P<0.05), while the mRNA and protein expression of ADAMTS1 were decreased (P<0.05, P<0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased(P<0.05), while the mRNA and protein expression of ADAMTS1 were increased (P<0.01, P<0.05). Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.

Management of Severe Bilateral Symptomatic Internal Carotid Artery Stenosis: Case Report and Literature Review.

Multiple strategies for tandem severe carotid artery stenosis are reported: bilateral carotid artery endarterectomy (CEA), bilateral carotid artery stenting (CAS), and hybrid procedures (CEA and CAS). The management is controversial, considering the reported high risk of periprocedural stroke, hemodynamic distress, and cerebral hyperperfusion syndrome. We present the case of a 64-year-old patient with severe symptomatic bilateral internal carotid artery stenosis (95% stenosis on the left internal carotid artery with recent ipsilateral watershed anterior cerebral artery-medial cerebral artery (ACA-MCA) and medial cerebral artery-posterior cerebral artery (MCA-PCA) ischemic strokes and 90% stenosis on the right internal carotid artery with chronic ipsilateral frontal ischemic stroke) managed successfully with staged CEA within a 3-day interval. The patient had a history of coronary angioplasty and stenting. Strategies for brain protection included shunt placement after the evaluation of carotid stump pressure, internal carotid backflow, and near-infrared spectroscopy. A collagen and silver-coated polyester patch was used to complete the endarterectomy using a 6.0 polypropylene continuous suture in both instances. Management also included neurological consults after extubation, dual antiplatelet therapy, head CT between the two surgeries, myocardial ischemia monitoring, and general anesthesia. Staged CEA with a small time interval between surgeries can be an option to treat tandem symptomatic carotid artery stenosis in highly selected patients. The decision should be tailored according to the patient's characteristics and should also be made by a cardiology specialist, a neurology specialist, and an anesthesia and intensive care physician.

Plaque enhancement of middle cerebral artery and pre-stroke diet are associated with prognosis of subacute ischemic stroke: A prospective high-resolution MR vessel wall imaging study

ObjectivesTo explore the value of middle cerebral artery (MCA) plaque characteristics in predicting the outcomes of subacute ischemic stroke and the incremental value of the previous diet on predictive performance. MethodsOne hundred and thirty-seven subacute ischemic stroke patients attributed to MCA plaques were included and analyzed in this prospective study. The National Institute of Health Stroke Scale (NIHSS) score, Mediterranean Diet Adherence Screener (MEDAS) score, and other clinical data were assessed. The plaque area, degree of stenosis, plaque burden, enhancement ratio, remodeling type, and intraplaque hemorrhage were measured using high-resolution MR vessel wall imaging (HR-VWI). Multivariable logistic regression analysis and receiver operating characteristic curve analysis were performed to assess the predictive performance of clinical and plaque characteristics for subacute ischemic stroke outcomes at 3 months. ResultsPatients with poor outcomes exhibited high NIHSS scores, and low MEDAS scores (P<0.001). Plaque burden, enhancement ratio, and degree of stenosis were significantly higher in patients with poor outcomes (P<0.001). Multivariate analyses further indicated that NIHSS score (P=0.001), MEDAS score (P=0.013), and enhancement ratio (P=0.011) were independent predictors of subacute ischemic stroke outcomes. The three models’ area under the curve (AUC) values were 0.811, 0.844, and 0.794. Combining these three factors resulted in an AUC of 0.908 (P<0.001). ConclusionsThe combination of NIHSS score, MEDAS score, and enhancement ratio showed significant superiority in the prognostic evaluation of subacute ischemic stroke. Clinical data combined with plaque characteristics improves the accuracy of 3-month outcome prediction on subacute ischemic stroke.

Trevo 3 Mm and/or AXS Catalyst5 for the Treatment of Medium Distal Vessel Occlusion Stroke-results from the ASSIST Registry.

The effect of endovascular therapy (EVT) on the outcome of stroke patients with amedium distal vessel occlusion (MDVO) is unclear. We report the results of MDVO patients treated with the 3 mm Trevo stent retriever (SR) and/or the AXS Catalyst5 distal access catheter. Data was derived from aprospective, multicenter global registry (ASSIST registry) which enrolled patients treated with operator preferred EVT technique at 71sites from January 2019 to January 2022. Three techniques were assessed: SR classic, direct aspiration, and acombined approach. Additional inclusion criteria were (a)EVT performed with the 3 mm Trevo SR and/or AXS Catalyst5 distal access catheter on the first pass and (b)an occlusion of the M2segment or M3segment of the middle cerebral artery or the A1, A2 or A3segment of the anterior cerebral artery. The primary outcome was achieving an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a90-day modified Rankin Scale (mRS) score of 0-2. Atotal of 155 patients (10.4% of the ASSIST population) were included. Most patients had an M2 occlusion (93.5%). First pass eTICI reperfusion was achieved in 43.1% of the patients. No modifying effect of the frontline technique was found. The rate of mRS 0-2 (overall 65.0%) did not significantly differ between groups. The data suggests that the Trevo 3 mm SR and/or the AXS Catalyst5 may be an option to treat medium distal vessel occlusion, but more data is needed to demonstrate safety and efficacy in this patient cohort. Further improvements are needed regarding materials and techniques to improve reperfusion results in this patient cohort in the future.

Characteristics, predictors and outcomes of early postoperative cerebral infarction on computed tomography in spontaneous intracerebral hemorrhage

Early postoperative cerebral infarction (ePCI) is a serious complication of spontaneous intracerebral hemorrhage (SICH). Yet, no study has specifically focused on ePCI among SICH patients. Our study aims to investigate the characteristics, predictors, and outcomes of ePCI observed on computed tomography (CT) within 72 h after surgery in patients with supratentorial SICH. Data from a single-center SICH study conducted from May 2015 to September 2022 were retrospectively analyzed. We described the characteristics of ePCI. Predictors were identified through logistic regression analysis, and the impact of ePCI on six-month mortality was examined using a Cox regression model. Subgroup analyses and the “E-value” approach assessed the robustness of the association between ePCI and mortality. A retrospective analysis of 637 out of 3938 SICH patients found that 71 cases (11.1%) developed ePCI. The majority of ePCI cases occurred on the bleeding side (40/71, 56.3%) and affected the middle cerebral artery (MCA) territory (45/71, 63.4%). Multivariable analysis showed that the Glasgow Coma Scale (GCS) score (odds ratio (OR), 0.62; 95% CI, 0.48–0.8; p < 0.001), bleeding volume (per 100 ml) (OR, 1.17; 95% CI, 1.03–1.32; p = 0.016), hematoma volume (per 10 ml) (OR, 1.14; 95%CI, 1.02–1.28; p = 0.023) and bilateral brain hernia (OR, 6.48; 95%CI, 1.71–24.48; p = 0.006) independently predicted ePCI occurrence. ePCI was significantly associated with increased mortality (adjusted hazard ratio (HR), 3.6; 95% CI, 2.2—5.88; p < 0.001). Subgroup analysis and E-value analysis (3.82—6.66) confirmed the stability of the association. ePCI is a common complication of SICH and can be predicted by low GCS score, significant bleeding, large hematoma volume, and brain hernia. Given its significant increase in mortality, ePCI should be explored in future studies.

Progesterone Receptor Agonist, Nestorone, Exerts Long-Term Neuroprotective Effects Against Permanent Focal Cerebral Ischemia in Adult and Aged Male Rats.

Stroke is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) is currently the most effective medicine for stroke; however, it has a narrow therapeutic time window (4.5h after symptom onset). We demonstrated that nestorone, a progesterone (P4) receptor agonist, exerted neuroprotective effects against transient focal cerebral ischemia 6h post-ischemic administration in adult male rats. This study examines its effects on permanent focal cerebral ischemia in adult and aged male rats, which are better models for evaluating treatment outcomes in typical stroke patients. Adult (6-month-old) or aged (18-month-old) male rats subjected to permanent middle cerebral artery occlusion (pMCAO) were continuously administered nestorone (10µg/day) or its vehicle (30% hydroxypropyl-β-cyclodextrin) for 7days via an osmotic pump subcutaneously implanted, starting at 18h post-pMCAO. Nestorone-treated adult male rats showed marked improvements in behavioral outcomes in the adhesive removal and rotarod tests and a significant reduction in infarct size compared to vehicle-treated rats 9 and 30days post-pMCAO. The same administration of nestorone resulted in apparently comparable neuroprotective effects in aged male rats. The inflammatory mediator NF-κB/p65 was increased in Iba-1 positive cells 24h post-pMCAO, but was significantly suppressed by subcutaneous injection of nestorone. These results suggested that nestorone exerts long-term neuroprotective effects against permanent focal cerebral ischemia in adult and aged male rats. Nestorone is thus a promising agent for post-stroke treatment owing to its wide age-independent therapeutic time window (18h after symptom onset), which is longer than that of tPA therapy.