Unilateral Middle Cerebral Artery Occlusion Research Articles

Impaired iron metabolism and cerebral perfusion patterns in unilateral middle cerebral artery stenosis or occlusion: Insights from quantitative susceptibility mapping

Background and purposeCerebral hypoperfusion caused by stenosis or occlusion of the middle cerebral artery (MCA) may be followed by impaired iron metabolism. We explored the association between iron changes of gray matter (GM) nuclei subregions and different cerebral perfusion patterns in patients with chronic unilateral middle cerebral artery (MCA) stenosis or occlusion using quantitative susceptibility imaging (QSM). MethodsSixty-one patients with unilateral MCA stenosis or occlusion were recruited and scored with Alberta-Stroke-Program-Early-CT-Score (ASPECTS) based on relative cerebral blood flow (rCBF) measurements to calculate the number of corresponding hypoperfusion subregions, and then divided into an extensive-hypoperfusion group (EH group), regional-hypoperfusion group (RH group), and normal-perfusion group (Control group) accordingly. The measured magnetic susceptibility of GM nuclei subregions was compared between the lesion and contralateral side for each group and among the three groups. Correlation analysis was performed to assess the relationships of magnetic susceptibility of GM nuclei with mean rCBF, National-Institutes-of-Health-stroke-scale (NIHSS) and modified-Rankin-scale (mRS) scores. ResultsMagnetic susceptibility in the putamen (PU) and globus pallidus (GP) at the lesion side was higher in the EH and RH groups compared with the contralateral side (all P < 0.05). Susceptibility in the lesion side PU and GP showed negative correlations with mean rCBF and positive correlations with NIHSS and mRS scores (all P < 0.05). ConclusionOur findings demonstrate that chronic cerebral hypoperfusion might be one cause of cerebral abnormal iron metabolism. In addition, magnetic susceptibility of PU and GP seems to be correlated with stroke scale scores, suggesting that iron deposition may play an important role in neurologic deficits after ischemic stroke.

Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution.

Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The presence of expression profiles, intercellular communications and signaling pathways of these three cell populations of PSD displayed a similar but more aggressive appearance with DEPR compared to MCAO and NC. Taken together, this study characterized the specific gene profile of endothelium, microglia and oligodendrocytes of hippocampal PSD by single cell sequencing, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.

Oxygen extraction fraction change in M1-M6 brain regions of patients with unilateral or bilateral middle cerebral artery occlusion.

Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) can be measured using arterial spin labeling (ASL) and quantitative susceptibility mapping (QSM) sequences, respectively. ASL and QSM sequences were performed on 13 healthy participants and 46 patients with unilateral or bilateral Middle cerebral artery (MCA) occlusion. M1-M3 and M4-M6 correspond to anterior, lateral, and posterior MCA territories within the insular ribbon and centrum semiovale, respectively. In patients with unilateral MCA occlusion, significant decreases in CBF were observed in the lesions in M1, M3, M5 and M6 regions, as well as in the contralateral M3 and M5 regions. The OEF of the lesion in the M1-M4 and M6 regions, and the contralateral M1-M3 regions were significantly higher. Additionally, the cerebral metabolic rate of oxygen (CMRO2) in the lesions of the M3 and M6 regions, and the contralateral M3 region, were significantly lower compared to the corresponding regions of healthy participants. For patients with bilateral MCA occlusion, the CMRO2 in the left M5 region and the right M3 and M6 regions were significantly lower than that in the corresponding regions of healthy participants. In conclusion, abnormal hemodynamics occur in the contralateral hemisphere of patients with unilateral MCA occlusion.

Vascular tortuosity is related to reduced thalamic volume after middle cerebral artery occlusion

ObjectivesThe mechanisms underlying secondary brain injury in remote areas remains unclear. This study aimed to investigate the relationship between vascular tortuosity and thalamic volume. Methods: In this study, we retrospectively analyzed sixty-five patients with unilateral middle cerebral artery occlusion (MCAO) who underwent magnetic resonance angiography. We compared the vascular tortuosity in patients with MCAO and controls, and analyzed the relationship between vascular tortuosity and thalamic volume. Results: Compared with controls, the MCAO group exhibited a significantly smaller thalamus volume on the affected side (5874 ± 183 mm3 vs. 5635 ± 383 mm3, p < 0.0001). The vascular tortuosity of the posterior cerebral artery (PCA) was higher in the MCAO group than in the controls (82.8 ± 17.3 vs. 76.7 ± 17.3, p = 0.040). Logistic regression analysis revealed that PCA tortuosity was an independent risk factor for reduced thalamic volume after MCAO (p = 0.034). In the subgroup analysis, only the 4-7-day group was not statistically different in thalamic volume between the MCAO and control groups. In the MCAO group, patients older than 60 years and female patients had a more tortuous PCA. Conclusion: Reduced thalamic volume after MCAO was associated with a tortuous PCA. After MCAO, PCA tortuosity increased more significantly in patients aged >60 years and in female patients.

Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review

BackgroundAcute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization.Case presentationThe patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation.ConclusionsAcute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.

CT Perfusion Alterations in Patients with Symptomatic and Asymptomatic Unilateral Middle Cerebral Artery Severe Stenosis or Occlusion.

To investigate the changes in CT perfusion between symptomatic and asymptomatic patients with unilateral middle cerebral artery severe stenosis or occlusion. A total of 64 consecutive patients with unilateral middle cerebral artery severe stenosis or occlusion admitted to the First Affiliated Hospital of Xinxiang Medical College from January 2019 to March 2022 were retrospectively analyzed and divided into the symptomatic group (n = 33), and the asymptomatic group (n = 31). Clinical data of the two groups were collected. Multivariate logistic regression analysis was performed to analyze the factors of symptomatic and asymptomatic MCA stenosis. A t-test was performed to compare the differences in cerebral perfusion parameters between the two groups. Multivariate logistic regression analysis indicated that glycosylated hemoglobin levels and high-density lipoprotein cholesterol levels were associated with the development of asymptomatic MCA severe stenosis or occlusion (odds ratio = 1.591 and 0.04, respectively). There were significant differences in CBV, MTT, and TTP between symptomatic and asymptomatic groups (p < 0.05). The CBF of the affected side in the symptomatic group was lower than that of the unaffected side (p < 0.05), whereas the asymptomatic group in CBF was not. Compared with the asymptomatic group, the CBF, MTT, and TTP of the affected side were significantly different (p < 0.05). In contrast, the cerebral perfusion parameters of the unaffected side were not significantly different (p > 0.05). The use of CT perfusion imaging to analyze the alterations in cerebral perfusion parameters in patients with symptomatic and asymptomatic MCA severe stenosis or occlusion was helpful in clinical diagnosis and selecting treatment strategies and judging the development of the disease.

αN-Acetyl β-Endorphin Is an Endogenous Ligand of σ1Rs That Regulates Mu-Opioid Receptor Signaling by Exchanging G Proteins for σ2Rs in σ1R Oligomers.

The opioid peptide β-endorphin coexists in the pituitary and brain in its αN-acetylated form, which does not bind to opioid receptors. We now report that these neuropeptides exhibited opposite effects in in vivo paradigms, in which ligands of the sigma type 1 receptor (σ1R) displayed positive effects. Thus, αN-acetyl β-Endorphin reduced vascular infarct caused by permanent unilateral middle cerebral artery occlusion and diminished the incidence of N-methyl-D-aspartate acid-promoted convulsive syndrome and mechanical allodynia caused by unilateral chronic constriction of the sciatic nerve. Moreover, αN-acetyl β-Endorphin reduced the analgesia of morphine, β-Endorphin and clonidine but enhanced that of DAMGO. All these effects were counteracted by β-Endorphin and absent in σ1R-/- mice. We observed that σ1Rs negatively regulate mu-opioid receptor (MOR)-mediated morphine analgesia by binding and sequestering G proteins. In this scenario, β-Endorphin promoted the exchange of σ2Rs by G proteins at σ1R oligomers and increased the regulation of G proteins by MORs. The opposite was observed for the αN-acetyl derivative, as σ1R oligomerization decreased and σ2R binding was favored, which displaced G proteins; thus, MOR-regulated transduction was reduced. Our findings suggest that the pharmacological β-Endorphin-specific epsilon receptor is a σ1R-regulated MOR and that β-Endorphin and αN-acetyl β-Endorphin are endogenous ligands of σ1R.

Changes in ultrasonic vocalizations after unilateral cerebral ischemia in a rat stroke model

Stroke frequently results in communication impairments that negatively impact quality of life and overall recovery, yet the biological mechanisms underlying these changes are not well understood. Ultrasonic vocalizations (USVs) in rodent models of disease and aging have been used to improve our understanding of the biological mechanisms that underlie vocal deficits and their response to interventions. Changes in USVs after middle cerebral artery occlusion (MCAO) in mice have been reported, yet rat models have significant anatomical and behavioral advantages over mice, including the ability to vocally train rats with an established paradigm. We sought to determine whether a unilateral MCAO rat stroke model provides a biologically and behaviorally relevant way to study post stroke vocalization deficits. We hypothesized that left MCAO would be associated with changes in USVs. Six weeks after MCAO or sham-control surgery, USVs were recorded in rats using an established mating paradigm. Stroke was associated with differences in USV acoustics including more frequent use of simple calls characterized by shorter durations and restricted bandwidths. These parameters were also found to correlate with post stroke lingual weakness. This is the first study to describe changes to rat USVs using a stroke model. These results suggest the unilateral MCAO rat stroke model is a biologically and behaviorally relevant model to understand how stroke affects vocal behaviors.

Prenatal alcohol exposure exacerbates acute sensorimotor deficits and impedes long-term behavioral recovery from the effects of an adult-onset cerebrovascular ischemic stroke.

Prenatal alcohol exposure (PAE) is a significant risk factor for developmental disability, although its health consequences across the lifespan are poorly understood. Here, we hypothesized that latent brain and systemic consequences of PAE influence resiliency to adult-onset neurological disease, specifically, cerebrovascular ischemic stroke. Pregnant Sprague-Dawley rats were exposed episodically to ethanol during the fetal neurogenic period. Adult (5months) male and female PAE and control offspring were subjected to endothelin-1-induced unilateral middle cerebral artery occlusion. In the acute injury phase outcomes including stroke volume and neurological, endocrine, and gut permeability markers were assessed. Because the effects of stroke in human populations evolve over months to years, we also assessed hippocampal- and amygdala-dependent memory function and social interaction preference up to 6months following a stroke, in middle-aged offspring. Prenatal alcohol exposure did not alter infarct volume, but significantly increased neurological deficits in both sexes, and impaired interhemispheric sensorimotor integration in PAE females. The IGF-1/IGFBP3 ratio, a measure of bioavailable IGF-1, was significantly reduced, while circulating levels of bacterial lipopolysaccharide, an inflammagen, were significantly increased in PAE males. In PAE females, the circulating IGF-1/IGFBP3 ratio was significantly increased and estradiol-17b levels were significantly reduced. The intestinal fatty acid binding protein, a surrogate marker of gut permeability was also significantly increased in PAE females. Longer-term deficits in hippocampal-associated memory and social interactions were observed in PAE males, while deficits in amygdala-dependent memory were observed in PAE females. PAE contributes to adverse effects on brain health and decreased resiliency in response to a common adult-onset neurovascular disease, cerebrovascular ischemic stroke.

Application of Three-Dimensional Arterial Spin Labeling Technique in the Assessment of Cerebral Blood Perfusion in Patients with Middle Cerebral Artery Occlusion: Analysis of Clinical Implications and Prognostic Factors.

Objective To explore the value of three-dimensional- (3D-) arterial spin labeling (ASL) technique in evaluating cerebral perfusion in patients with unilateral middle cerebral artery occlusion (MCAO) and to observe the influencing factors of poor prognosis via long-term follow-up of patients who survived the disease. Methods The clinical data of 60 patients with unilateral middle cerebral artery (MCA) M1 segment occlusion diagnosed by magnetic resonance angiography (MRA) from January 2018 to January 2022 were retrospectively analyzed. All patients were examined by routine MRI, MRA, and 3D-ASL, in which two postlabeling delays (PLDs; 1525 ms and 2525 ms) were used in 3D-ASL. Cerebral blood flow (CBF) in the regions of interest (ROIs) of MCA on the affected side and the mirror side was measured. The clinical data and laboratory indexes of patients were collected and evaluated by clinical scales. With the modified Rankin Score (mRS) as the outcome indicator, patients were assigned to either the poor or the good prognosis group to analyze the factors influencing patient prognosis via univariate and multivariate analyses. Results Among unilateral MCAO patients, there was a significant difference in the CBF of the affected side between the PLD 1525 ms and 2525 ms groups (P < 0.05), but there was no significant difference in the CBF of the mirror side (P > 0.05). Compared with the mirror side, 43 cases (71.7%) of the affected CBF presented with hypoperfusion, 9 cases (15.0%) with normal perfusion, and 8 cases (13.3%) with hyperperfusion. Age, NIHSS score, collateral circulation, and homocysteine (Hcy) were identified by multivariate Logistic regression analysis as independent risk factors for adverse outcomes. Conclusion MCAO can lead to cerebral blood perfusion decline, and 3D-ASL technique can evaluate the post-MCAO cerebral blood perfusion level. Old age, high NIHSS scores, poor collateral circulation, and high Hcy levels are associated with poor clinical outcomes.

The value of whole-brain CT perfusion imaging combined with dynamic CT angiography in the evaluation of pial collateral circulation with middle cerebral artery occlusion.

Middle cerebral artery (MCA) occlusion is extremely common, especially unilateral artery, which can result in a significant incidence of cerebral infarction. To assess the value of whole-brain computed tomography perfusion (CTP) imaging combined with dynamic CT angiography (dCTA) in the evaluation of pial collateral circulation in patients with MCA occlusion. Whole-brain CTP and dCTA images were acquired in 58 patients with unilateral MCA occlusion. All patients were divided into three groups according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score (by CTA). The CTP parameters were analysed, including relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transit time (rMTT), and relative time to peak (rTTP). Patients were followed up with the modified Rankin scale (mRS). All cases in this study were confirmed by DSA. The CTP parameters of the MCA blood supply area on the affected side of patients with different degrees of stenosis were significantly different from those on the unaffected side. There are significant differences in the CTP parameters and openings of the Willis circle in patients with different degrees of stenosis. Significant differences were found in the number of patients with good prognosis. Whole-brain CT perfusion combined with dynamic CTA can structurally and functionally evaluate the establishment of pial collateral circulation and its effect on cerebral hemodynamic changes.

Multiparametric Monitoring of Early Pathophysiological Changes in a Porcine Model of Sequential Focal and Global Cerebral Ischemia

Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiO2) and cerebral blood flow (CBF) to characterize a porcine model of sequential middle cerebral artery occlusion (MCAO) and common carotid artery occlusion (CCAO). Eight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e., <50% in both ptiO2 and CBF) was followed by additional bilateral CCAO. Neurodegenerative changes were detected by Fluoro-Jade B (FJB) staining. Only 1 of 8 animals demonstrated a decrease of >50% in both ptiO2 and CBF after MCAO. Additional CCAO in 7 pigs led to a significant reduction of both ipsilateral and contralateral ptiO2 (P < 0.01) but not of CBF. There was no difference in ptiO2 and FJB positive area between hemispheres in this group. Measurement of ptiO2 correlated negatively with the FJB positive area (P < 0.05). Intraparenchymal multiparametric measurements of acute changes in ptiO2 and CBF were variable after MCAO. Bilateral CCAO led to a consistent decrease in ptiO2 and correlated with early degenerative histologic changes, but CBF did not. Real-time procedural ptiO2 monitoring could provide useful guidance in large animal ischemia models. Feasibility in the context of global cerebral hypoperfusion is demonstrated.

Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIαCreERT2/+/L-PGDS+/+, and CaMKIIαCreERT2/+/L-PGDSflox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIαCreERT2/+/L-PGDS+/+ and CaMKIIαCreERT2/+/L-PGDSflox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIαCreERT2/+/L-PGDS+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIαCreERT2/+/L-PGDSflox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.

Leptomeningeal collateral flow in patients with middle cerebral artery occlusion assessed by transcranial Doppler.

To explore the application value and clinical significance of transcranial Doppler(TCD)in assessing leptomeningeal collateral flow (LMF) status in patients with unilateral middle cerebral artery (MCA) occlusion. Medical records of patients with unilateral MCA occlusion confirmed by digital subtraction angiography (DSA) were analyzed retrospectively. The patients were divided into three groups according to LMF status, and the laboratory and imaging results were collected. Cerebral blood flow velocity (CBFV) of MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) on the affected side (ipsilateral, i) and the healthy side (contralateral, c) were measured and recorded by TCD. The results of CBFV changes detected by TCD were compared with those of DSA, and the correlation between CBFV changes and LMF status was analyzed. Eighty-four patients with unilateral MCA occlusion were included. CBFViACA and CBFViPCA were significantly faster than CBFVcACA and CBFVcPCA in patients with good LMF status (p<.05). There was a significant positive correlation between CBFViACA and LMF status (r = 0.697, p<.001). There was statistical significance in receiver operating characteristic curve analysis of CBFViACA and CBFViPCA (p<.05). The area under the curve of CBFViACA and CBFViPCA, respectively, was 0.879 and 0.678, and the best cutoff value was 82 and 60.5 cm/s. TCD can assess LMF status by detecting the changes of flow velocity of intracranial vessels. CBFV of ACA and PCA in patients with MCA occlusion is significantly correlated with LMF status by DSA. Assessing LMF status, CBFViACA, CBFViACA/CBFVcACA, and CBFViACA/CBFViMCA has the great diagnostic value, which is of great significance in guiding MCA occlusion patients to choose individualized treatment.

Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia.

Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.

Analysis of cerebral perfusion of leptomeningeal branch and perforating branch of unilateral middle cerebral artery with severe stenosis or occlusion based on multi-delay arterial spin labeling

Objective: To compare the cerebral perfusion differences between the symptomatic patients and the asymptomatic patients with unilateral middle cerebral artery (MCA) severe stenosis or occlusion by using three post labeling delays (PLD) of the three-dimensional pseudo-continuous arterial spin labeling (pCASL) technique. Methods: The clinical characteristics and ASL data of the 27 patients with severe stenosis or occlusion of unilateral MCA (18 symptomatic, 9 asymptomatic) were prospectively enrolled from April 2018 to November 2019 in the Department of Radiology of China-Japan Friendship Hospital. There were 16 males and 11 females, age range from 29 to 85 (55±13) years. According to the symptoms, they were divided into symptomatic group (18 cases) and asymptomatic group (9 cases). The parameters of cerebral blood flow (CBF), mean cerebral blood flow (mCBF), arterial transit time (ATT) and arterial cerebral blood volume (aCBV) were obtained using the Cereflow software. One-way multivariate analysis of variance (one-way MANOVA) was used to compare the differences of cerebral perfusion parameters between symptomatic group and asymptomatic group, and between the affected side and the control side in the two groups. Two-way ANOVA was used to evaluate the effects of symptoms, hemisphere (affected and control side), PLD times (1.5, 2.0 and 2.5 s) and the interaction between the two factors. Results: The CBF of the affected leptomeningeal branch and perforating branch of MCA in symptomatic group was lower than that in asymptomatic group [(36.8±10.2) ml·100 g-1·min-1 versus (46.6±13.9) ml·100 g-1·min-1, F(1, 75)=13.279, P=0.000 49; (32.3±8.3) ml·100 g-1·min-1 versus (36.2±7.5) ml·100 g-1·min-1, F (1, 75)=4.065, P=0.047], and there was no interaction between the symptom and PLD [F(2, 75) =0.061, P=0.940]. In the symptomatic group, the CBF of the leptomeningeal branch and perforating branch of MCA in affected side was lower than that in control side [(36.8±10.2) ml·100 g-1·min-1 versus (43.7±10.0) ml·100 g-1·min-1, F(1, 102)=12.559, P=0.000 59; (32.3±8.3) ml·100 g-1·min-1 versus (36.4±8.0) ml·100 g-1·min-1, F(1, 102)=6.493, P=0.012]. In the symptomatic group, the CBF of leptomeningeal branch of MCA when PLD was 2.5 s was 7.34 ml·100 g-1·min-1, which were higher than that when PLD of 1.5 s (95%CI: 0.72-13.9, P=0.03). There was no interaction between PLD and hemisphere [F(2, 102) =0.307, P=0.736]. Conclusions: The collateral circulation in the blood supply area of MCA in asymptomatic patients with severe unilateral MCA stenosis or occlusion is more abundant than that in symptomatic patients. ASL can be an effective technique for evaluating the cerebral perfusion of collateral circulation in patients with severe stenosis or occlusion of MCA.

Chronic Low-Dose Alcohol Consumption Attenuates Post-Ischemic Inflammation via PPARγ in Mice.

Ischemic stroke is one of the leading causes of death and permanent disability in adults. Recently, we found that light alcohol consumption (LAC) suppresses post-ischemic inflammatory response, which plays an important role in ischemic brain damage. Our goal was to determine the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in the anti-inflammatory effect of LAC against transient focal cerebral ischemia. In in vivo study, male C57BL/6J wild type (WT) and endothelial-specific conditional PPARγ knockout mice were gavage fed with 0.7 g/kg/day ethanol or volume-matched water daily for 8 weeks. From the 7th week, 3 mg/kg/day GW9662 (a selective PPARγ antagonist) was intraperitoneally given for two weeks. Cerebral ischemia/reperfusion (I/R) injury and expression of manganese superoxide dismutase (MnSOD) and adhesion molecules, neutrophil infiltration, and microglial activation in the cerebral cortex before and following a 90 min unilateral middle cerebral artery occlusion (MCAO)/24 h reperfusion were evaluated. In in vitro study, the impact of chronic alcohol exposure on expression of PPARγ and MnSOD in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs) was measured. PPARγ and MnSOD were significantly upregulated in the cerebral cortex of ethanol-fed WT mice and low-concentration ethanol-exposed C57BL/6J MBMVECs. GW9662 significantly inhibited alcohol-induced upregulation of MnSOD. Eight-week ethanol feeding significantly reduced cerebral I/R injury and alleviated the post-ischemic inflammatory response (upregulation of intercellular adhesion molecule-1 (ICAM-1) and E-selectin, microglial activation, and neutrophil infiltration). Treatment with GW9662 and endothelial-specific conditional knockout of PPARγ did not alter cerebral I/R injury and the inflammatory response in the control mice but abolish the neuroprotective effect in ethanol-fed mice. In addition, GW9662 and endothelial-specific conditional knockout of PPARγ diminished the inhibitory effect of LAC on the post-ischemic expression of adhesion molecules and neutrophil infiltration. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing the post-ischemic inflammation via activation of PPARγ.

Can 3D Pseudo-Continuous Territorial Arterial Spin Labeling Effectively Diagnose Patients With Recanalization of Unilateral Middle Cerebral Artery Stenosis?

Unilateral middle cerebral artery (MCA) stenosis, as an independent risk factor for stroke, requires an intervention operation for vessel recanalization. Accurate perfusion measurement is thus essential after the operation. To explore the feasibility of three-dimensional (3D) pseudo-continuous territorial arterial-spin-labeling (tASL) in evaluating MCA recanalization. Prospective and longitudinal. Forty-seven patients with unilateral MCA stenosis or occlusion. A 3.0 T, 3D time-of-flight fast-field-echo magnetic resonance (MR) angiography sequence, spin-echo echo-planar diffusion-weighted imaging sequence, 3D fast-spin-echo pseudo-continuous ASL (pcASL) and tASL sequences. All patients underwent MR examination before and after MCA recanalization and scored using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admission and discharge. An mRS score <2 was defined as a good prognosis. 3D-pcASL and tASL cerebral blood flow (CBF) maps were obtained, and the corresponding Alberta Stroke Program Early CT Score (ASPECTS)-based scores were evaluated. The Kolmogorov-Smirnov test, intra-class correlation coefficient, paired t-test, receiver operating characteristic (ROC) curve, and multivariable logistic regression analysis. After recanalization, tASL derived absolute CBFs between the affected and contralateral sides were significantly higher than before the operation (mean: 34.3 ± 8.5 mL/100 g/min vs. 40.6 ± 9.2 mL/100 g/min, 42.6 ± 9.8 mL/100 g/min vs. 43.5 ± 9.9 mL/100 g/min, both P < 0.05). In ROC analysis, tASL provided good prognosis (area under ROC curve [AUC]=0.829; 95% CI: 0.651-1.000, P < 0.05), while pcASL had lower prognostic value (AUC=0.760; 95% CI: 0.574-0.946, P < 0.05). The NIHSS score before recanalization, pcASL, and tASL-based ASPECTS scores were significantly associated with good clinical outcome (P < 0.05). Multivariable analysis revealed that ASPECTS-based scores of pcASL and tASL before and after surgery were independent predictors of good clinical outcome (all P < 0.05). DATA CONCLUSION: tASL can determine hypoperfusion in the responsible vascular perfusion area and predict clinical outcome. 4 TECHNICAL EFFICACY: Stage 2.

Evaluating the Effect of Arterial Pulsation on Cerebrospinal Fluid Motion in the Sylvian Fissure of Patients with Middle Cerebral Artery Occlusion Using Low b-value Diffusion-weighted Imaging.

PurposeDecrease in signal of the cerebrospinal fluid (CSF) on low b-value diffusion weighted image (DWI) due to non-uniform flow can provide additional information regarding CSF motion. The purpose of the current study was to evaluate whether arterial pulsations constitute the driving force of CSF motion.MethodsWe evaluated the CSF signals within the Sylvian fissure on low b-value DWI in 19 patients with unilateral middle cerebral artery (MCA) occlusion. DWI with b-value of 500 s/mm2 was evaluated for a decrease in CSF signal within the Sylvian fissure including the Sylvian vallecula and lower, middle, and higher Sylvian fissures and graded as follows: the same as contralateral side; smaller signal decrease than that on contralateral side; and no signal decrease. MR angiography (MRA) findings of MCA were graded as follows: the same as contralateral, lower signal than contralateral signal, and no signal. In 15 patients, regional cerebral blood flow (rCBF) was evaluated using single-photon emission computed tomography (SPECT) studies and graded as > 90%, 90%–70%, and < 70% rCBF compared to contralateral. The correlations between the gradings were evaluated using G likelihood-ratio test.ResultsThere was no statistically significant correlation between the MRA and low b-value DWI gradings of CSF in all areas. There were statistically significant correlations between the decreases in CBF on SPECT and CSF signals in the middle Sylvian fissure.ConclusionThe driving force of CSF pulsation in the Sylvian sinus may be related to the pulsations of the cerebral hemisphere rather than direct arterial pulsations.

Alleviation of brain injury by applying TGN-020 in the supraoptic nucleus via inhibiting vasopressin neurons in rats of focal ischemic stroke

AimsTo understand mechanisms underlying vasopressin hypersecretion in stroke and its association with brain injury, we investigated effects of blocking aquaporin 4 (AQP4) in the supraoptic nucleus (SON) on vasopressin neuronal activity and cerebral injuries in male rats of unilateral middle cerebral artery occlusion (MCAO). Main methodsEstablishing MCAO model without or with microinjection of TGN-020 into the SON, performing Western blots and immunohistochemistry and analyzing the expression levels and spatial distribution of functional proteins in the SON and/or the cerebral cortex. Key findingsMCAO increased plasma vasopressin levels, caused neurological damage and increased glycogen synthase kinase 3β (GSK-3β) in the SON and the cortex of MCAO side. In the SON, MCAO significantly increased c-Fos in vasopressin neurons and astrocytic somata in the ventral glial lamina. MCAO significantly reduced glial fibrillary acidic protein (GFAP) and AQP4 around vasopressin neurons, which accompanied separation of GFAP from AQP4. By contrast, blocking AQP4 by microinjection of TGN-020 into the SON blocked MCAO-evoked GSK-3β increase as well as the reduction of AQP4 relative to GFAP around vasopressin neurons in the SON. In the cortex, TGN-020 in the SON also blocked MCAO-evoked increase in GSK-3β while reduced neurological damages. SignificanceThese findings indicate that MCAO disrupts interactions of GFAP with AQP4 in astrocytic processes in the SON, which increases vasopressin neuronal activity. Blocking AQP4 in the SON can block abnormal activation of vasopressin neurons and alleviate ischemic brain injury, which provides novel targets for alleviating ischemic brain injury.