Unusual and Rare Causes of Monocular Elevation Deficit.

INTRODUCTION: To study the rare and unusual causes of monocular elevation deficit. METHODS: Five patients presenting to us with diplopia and elevation deficit were thoroughly examined and were found to have monocular elevation deficit due to rare causes. OBSERVATIONS: All five were found to have different underlying etiologies - iatrogenic, sphenoid wing meningioma, cysticercosis, sarcoidosis and mid brain infarct, and were managed appropriately. DISCUSSION: Monocular Elevation Deficit can occur due to a variety of causes. Having a high index of suspicion for the more serious etiologies is of utmost importance. Thorough clinical examination and imaging help clinch the diagnosis.

Astrocytes constitute the major TNF-α-producing cell population in the infarct cortex in dMCAO rats receiving intravenous MSC infusion.

Recent studies report that inhibiting TNF-α might be a novel therapeutic strategy for managing brain ischemia. Our previous study reported that mesenchymal stem cell (MSC) transplantation could suppress TNF-α level in both serum and brain. However, the cell type(s) that contribute to the production of TNF-α during ischemia following MSC transplantation has not been well studied. In the present study, we found by fluorescent immunohistochemistry, that 7.95 ± 6.17% of TNF-α+ cells co-expressed Iba-1 in the infarct area of dMCAO rats, a majority of which were found to be CD68+ (activated microglia), suggesting that resident microglial population were not the major source of TNF-α expression. 68.49 ± 5.12% of the TNF-α+ cells in the infarct area could be labeled by GFAP, a specific marker for astrocytes, indicating that resident GFAP+ astrocytes might be the major source of TNF-α expression in the infarct area. In addition to the infarct area, the GFAP+/TNF-α+ double-positive astrocytes accounted for 73.68 ± 7.48% of the TNF-α+ cells in striatum and corpus callosum. The infiltrating cells, including monocytes and lymphocytes, were not the main source of TNF-α either. In response to MSC transplantation, the total TNF-α+ cells as well as the percentage of TNF-α-expressing astrocytes were significantly reduced in the infarct area, suggesting that MSC transplantation could suppress the expression of TNF-α by astrocytes. Taken together, the results demonstrated that resident astrocytes, but not microglia, were the major source of TNF-α expression and could be suppressed by MSC infusion.

Uric Acid Neuroprotection Associated to IL-6/STAT3 Signaling Pathway Activation in Rat Ischemic Stroke.

Despite the promising neuroprotective effects of uric acid (UA) in acute ischemic stroke, the seemingly pleiotropic underlying mechanisms are not completely understood. Recent evidence points to transcription factors as UA targets. To gain insight into the UA mechanism of action, we investigated its effects on pertinent biomarkers for the most relevant features of ischemic stroke pathophysiology: (1) oxidative stress (antioxidant enzyme mRNAs and MDA), (2) neuroinflammation (cytokine and Socs3 mRNAs, STAT3, NF-κB p65, and reactive microglia), (3) brain swelling (Vegfa, Mmp9, and Timp1 mRNAs), and (4) apoptotic cell death (Bcl-2, Bax, caspase-3, and TUNEL-positive cells). Adult male Wistar rats underwent intraluminal filament transient middle cerebral artery occlusion (tMCAO) and received UA (16 mg/kg) or vehicle (Locke's buffer) i.v. at 20 min reperfusion. The outcome measures were neurofunctional deficit, infarct, and edema. UA treatment reduced cortical infarct and brain edema, as well as neurofunctional impairment. In brain cortex, increased UA: (1) reduced tMCAO-induced increases in Vegfa and Mmp9/Timp1 ratio expressions; (2) induced Sod2 and Cat expressions and reduced MDA levels; (3) induced Il6 expression, upregulated STAT3 and NF-κB p65 phosphorylation, induced Socs3 expression, and inhibited microglia activation; and (4) ameliorated the Bax/Bcl-2 ratio and induced a reduction in caspase-3 cleavage as well as in TUNEL-positive cell counts. In conclusion, the mechanism for morphological and functional neuroprotection by UA in ischemic stroke is multifaceted, since it is associated to activation of the IL-6/STAT3 pathway, attenuation of edematogenic VEGF-A/MMP-9 signaling, and modulation of relevant mediators of oxidative stress, neuroinflammation, and apoptotic cell death.

Human Umbilical Cord-Derived Mesenchymal Stem Cell Therapy Effectively Protected the Brain Architecture and Neurological Function in Rat After Acute Traumatic Brain Injury.

Intracranial hemorrhage from stroke and head trauma elicits a cascade of inflammatory and immune reactions detrimental to neurological integrity and function at cellular and molecular levels. This study tested the hypothesis that human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy effectively protected the brain integrity and neurological function in rat after acute traumatic brain injury (TBI). Adult male Sprague-Dawley rats (n = 30) were equally divided into group 1 (sham-operated control), group 2 (TBI), and group 3 [TBI + HUCDMSC (1.2 × 106 cells/intravenous injection at 3 h after TBI)] and euthanized by day 28 after TBI procedure. The results of corner test and inclined plane test showed the neurological function was significantly progressively improved from days 3, 7, 14, and 28 in groups 1 and 3 than in group 2, and group 1 than in group 3 (all P < 0.001). By day 28, brain magnetic resonance imaging brain ischemic volume was significantly increased in group 2 than in group 3 (P < 0.001). The protein expressions of apoptosis [mitochondrial-bax positive cells (Bax)/cleaved-caspase3/cleaved-poly(adenosine diphosphate (ADP)-ribose) polymerase], fibrosis (Smad3 positive cells (Smad3)/transforming growth factor-ß), oxidative stress (NADPH Oxidase 1 (NOX-1)/NADPH Oxidase 2 (NOX-2)/oxidized-protein/cytochrome b-245 alpha chain (p22phox)), and brain-edema/deoxyribonucleic acid (DNA)-damaged biomarkers (Aquaporin-4/gamma H2A histone family member X ( (γ-H2AX)) displayed an identical pattern to neurological function among the three groups (all P < 0.0001), whereas the protein expressions of angiogenesis biomarkers (vascular endothelial growth factor/stromal cell-derived factor-1α/C-X-C chemokine receptor type 4 (CXCR4)) significantly increased from groups 1 to 3 (all P < 0.0001). The cellular expressions of inflammatory biomarkers (cluster of differentiation 14 (+) cells (CD14+)/glial fibrillary acidic protein positive cells (GFAP+)/ a member of a new family of EGF-TM7 molecules positive cells (F4/80+)) and DNA-damaged parameter (γ-H2AX) exhibited an identical pattern, whereas cellular expressions of neural integrity (hexaribonucleotide Binding Protein-3 positive cells (NeuN+)/nestin+/doublecortin+) exhibited an opposite pattern of neurological function among the three groups (all P < 0.0001). Xenogeneic HUCDMSC therapy was safe and it significantly preserved neurological function and brain architecture in rat after TBI.

In vivo Monitoring and Assessment of Exogenous Mesenchymal Stem Cell-Derived Exosomes in Mice with Ischemic Stroke by Molecular Imaging.

PURPOSE: Mesenchymal stem cell-derived exosomes (MSC-exos) are considered an important restorative treatment for ischemic stroke. However, the migration ability and survival of exogenous MSC-exos remain unclear. Here, we investigated whether MSC-exos migrate into the ischemic brain and play a protective role against ischemic stroke. METHODS: MSC-exos labeled with DiR were injected intravenously into mice with ischemic stroke. Near-infrared fluorescence (NIRF) images were obtained on days 0, 1, 3, 5, 7, 10, and 14, and magnetic resonance (MR) images were obtained on days 1, 7 and 14. On day 14, the functional outcomes, angiogenesis, neurogenesis, and white matter remodeling were assessed, and Western blot assays were performed. RESULTS: Fluorescence signals from the MSC-exos appeared in the injured brain from day 1 and peaked on day 3. The immunofluorescence staining of the brain samples revealed that the MSC-exos were localized in neurons. The behavioral scores and T2-weighted imaging indicated that the MSC-exos improved neurological functional recovery after stroke. In addition, the in vivo MR-diffusion tensor imaging (DTI) indicated that the exogenous MSC-exos increased the fractional anisotropy (FA) value, fiber length, and fiber number ratio. Furthermore, in the mice with ischemic stroke treated with MSC-exos, angiogenesis and neurogenesis were significantly improved, and the expression of IL-1ß was reduced. CONCLUSION: MSC-exos can migrate into the brains of mice with ischemic stroke and exert therapeutic effects against ischemic stroke; therefore, MSC-exos may have broad clinical applications in the future.

Overexpression of Slit2 decreases neuronal excitotoxicity, accelerates glymphatic clearance, and improves cognition in a multiple microinfarcts model.

BACKGROUND: Cerebral microinfarcts (MIs) lead to progressive cognitive impairments in the elderly, and there is currently no effective preventative strategy due to uncertainty about the underlying pathogenic mechanisms. One possibility is the dysfunction of GABAergic transmission and ensuing excitotoxicity. Dysfunction of GABAergic transmission induces excitotoxicity, which contributes to stroke pathology, but the mechanism has kept unknown. The secreted leucine-rich repeat (LRR) family protein slit homologue 2 (Slit2) upregulates GABAergic activity and protects against global cerebral ischemia, but the neuroprotective efficacy of Slit2 against MIs has not been examined. METHODS: Middle-aged Wild type (WT) and Slit2-Tg mice were divided into sham and MI treatment groups. MIs were induced in parietal cortex by laser-evoked arteriole occlusion. Spatial memory was then compared between sham and MI groups using the Morris water maze (MWM) task. In addition, neuronal activity, blood brain barrier (BBB) permeability, and glymphatic clearance in peri-infarct areas were compared using two-photon imaging, while GABAergic transmission, microglial activation, neuronal loss, and altered cortical connectivity were compared by immunofluorescent staining or western blotting. RESULTS: Microinfarcts increased the amplitude and frequency of spontaneous intracellular Ca2+ signals, reduced neuronal survival and connectivity within parietal cortex, decreased the number of GABAergic interneurons and expression of vesicular GABA transporter (VGAT), induced neuroinflammation, and impaired both glymphatic clearance and spatial memory. Alternatively, Slit2 overexpression attenuated dysfunctional neuronal Ca2+ signaling, protected against neuronal death in the peri-infarct area as well as loss of parietal cortex connectivity, increased GABAergic interneuron number and VGAT expression, attenuated neuroinflammation, and improved both glymphatic clearance and spatial memory. CONCLUSION: Our results strongly suggest that overexpression of Slit2 protected against the dysfunction in MIs, which is a potential therapeutic target for cognition impairment in the elderly.

Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion.

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated the cognitive impairment and pathomechanism associated with tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH). We performed middle cerebral artery occlusion (MCAO) surgery in rats to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic function. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was combined with MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the peri-infarct area when CCH was combined. Synergistic accentuation of tauopathy was evident in the white matter. Microtubules in the neuronal axon and myelin sheath showed partial colocalization with the hyperphosphorylated tau, whereas oligodendrocytes showed near-complete colocalization. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest a hypothesis that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through the glymphatic system. Therapeutic strategies to improve the clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.

Association of neonatal inflammatory markers and perinatal stroke subtypes.

OBJECTIVE: To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients. METHODS: This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls. RESULTS: A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy. CONCLUSIONS: Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.

Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings.

This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4-/- ) (n = 6 per each TLR4-/- group) mice were categorized into sham control (SCB6 ), SCTLR4-/- , ISB6 , ISTLR4-/- , ISB6  + Mel (i.p. daily administration) and ISTLR4-/- + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK-α/p-NF-κB/nuclear-NF-κB/nuclear-IRF-3&7/IL-1ß/IL-6/TNF-α/IFN-γ) and oxidative stress (NOX-1/NOX-2/ASK1/p-MKK4&7/p-JNK/p-c-JUN) downstream pathways as well as mitochondrial-damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group ISB6 , lowest in groups SCB6 and SCTLR4-/- , lower in group ISTLR4-/- + Mel than in groups ISTLR4-/- and ISB6  + Mel and lower in group ISB6  + Mel than in group ISTLR4-/- (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4-88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy.

Asiaticoside Alleviates Cerebral Ischemia-Reperfusion Injury via NOD2/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BACKGROUND Cerebral ischemia-reperfusion injury (CIRI) remains a serious health problem. Centella asiatica formulations are used to treat central nervous system disorders. In the present study, asiaticoside, an extract of the plant Centella asiatica, was investigated in CIRI in vivo and vitro. MATERIAL AND METHODS We made a CIRI model in vivo in SD rats treated by middle cerebral artery occlusion, and a cell model of ischemia-reperfusion injury was made in PC12 cells treated by deprivation of oxygen and glucose/restoration. CIRI in vivo was assessed by scores of neurological functions, encephaledema, and cerebral infarction area. Inflammation level and oxidative stress level were detected by the appropriate kits. TUNEL assay was performed for assessment of cell apoptosis and Western blot analysis was performed to assess protein expression levels. CCK8 assay was performed for evaluation of cell survival and flow cytometer was used to detect cell apoptosis in vitro. RESULTS Nervous function injury, brain edema, cell apoptosis, infarct size, apoptosis-related protein expressions, and protein expressions of the NOD2/MAPK/NF-kappaB signaling pathway in the CIRI model were all reversed by asiaticoside in rats. The cell apoptosis, inflammation level, and oxidative stress level in the model of cerebral ischemia-reperfusion injury were reduced by asiaticoside. The effects of asiaticoside on CIRI were reversed by NOD 2 agonists. CONCLUSIONS Asiaticoside showed a protective effect against cerebral ischemia-reperfusion injury via the NOD2/MAPK/NF-kappaB signaling pathway. These findings are vital for future research on use of asiaticoside in CIRI, providing a new avenue for alleviating CIRI.

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

Endovascular Vertebral Artery Transposition Using Flow Reversal Technique for Left Subclavian Artery Stump Syndrome.

BACKGROUND: Cerebellar strokes are a rare complication related to thoracic endovascular aortic repair (TEVAR). This can manifest in an indolent manner or as a neurological catastrophe. Often it is unclear when a surgical intervention would be needed. Patients at risk for this relatively rare complication are not easily identified. CASE: We describe an endovascular option with flow reversal for left vertebral artery transposition using stent grafts for relocating arterial inflow and excluding a floating thrombus at the proximal subclavian artery (SCA) related to a previous TEVAR. CONCLUSIONS: Ligation of the subclavian artery proximal to the vertebral artery should be considered when performing a carotid subclavian bypass for elective TEVAR. This case details a unique, less invasive approach for vertebral artery transposition and thrombus exclusion in a high-risk patient with previous neck dissection.

Young male with syphilitic cerebral arteritis presents with signs of acute progressive stroke: A case report.

INTRODUCTION: Neurosyphilis is a chronic infection of the central nervous system that is commonly found in adult with long latency periods. Neurosyphilis-attributed deaths in young patients have grown exponentially in the past decade, yet there have been few studies on the early stages of neurosyphilis. PATIENT CONCERNS: A young male patient with syphilitic cerebral arteritis was evaluated in our clinic for the clinical signs of progressive ischemic stroke. DIAGNOSIS: The progression of syphilitic cerebral arteritis was observed through computed tomography imaging, magnetic resonance imaging, magnetic resonance angiogram, and transcranial color Doppler. The pathological changes and clinical outcomes were reviewed. In this specific case, the development of syphilitic cerebral arteritis was dynamic, continuous, and rapid. The pathogenesis was related to Heubner arteritis, in which the formation of a mural thrombus (MT) causes the severe obstruction of blood flow without complete occlusion, leading to an increased risk of infarction. In this patient, formation of the MT resulted in the infarction of the smaller vessels and narrowing of the larger vessels. The partial dislodgment of the MT from the arterial wall of the larger vessels occluded the smaller vessels, leading to infarction. INTERVENTIONS: Standard pharmacotherapy for the treatment of the cerebral infarction and a single course of penicillin were applied. OUTCOMES: Muscle strength was recovered. The Glasgow Coma Scale score was 15, whereas the NIH Stroke Scale score was 0. The increase in blood flow of the right MCA was accompanied by severe stenosis with compensation of the anterior communicating artery. In addition, moderate to severe stenosis of the right vertebral artery and the basilar artery was suspected. There was a possibility that the right posterior communicating artery was recruited for compensation. CONCLUSION: Progressive stroke was the initial symptom of the neurosyphilis. Disease progression is rapid and difficult to control with a single course of penicillin.

Postoperative cerebral oxygenation was not associated with new brain injury in infants with congenital heart disease.

OBJECTIVE: The aim of this study was to evaluate postoperative indices of cerebral oxygenation and autoregulation in infants with critical congenital heart disease in relation to new postoperative ischemic brain injury. METHODS: This prospective, clinical cohort included 77 infants with transposition of the great arteries (N = 19), left ventricular outflow tract obstruction (N = 30), and single ventricle physiology (N = 28) undergoing surgery at 30 days or less of life. Postoperative near-infrared spectroscopy and physiologic monitoring were applied to extract mean arterial blood pressure, regional cerebral oxygen saturation, fractional tissue oxygen extraction, and regional cerebral oxygen saturation mean arterial blood pressure correlation coefficient (≥0.5 considered sign of impaired cerebral autoregulation). New postoperative ischemic injury was defined as moderate-severe white matter injury or focal infarction on magnetic resonance imaging. Low cardiac output syndrome was measured as lactate greater than 4 mmol/L with pH less than 7.30. RESULTS: After surgery, regional cerebral oxygen saturation was decreased in all congenital heart disease groups with a notable increase in regional cerebral oxygen saturation between 6 and 12 hours after surgery, on average with a factor of 1.4 (range, 1.1-2.4). Both single ventricle physiology and postoperative low cardiac output syndrome were associated with lower regional cerebral oxygen saturation and increased time with correlation coefficient of 0.5 or greater. New postoperative ischemic injury was seen in 39 patients (53%) and equally distributed across congenital heart disease groups. Postoperative regional cerebral oxygen saturation, fractional tissue oxygen extraction, and correlation coefficient were not independently associated with new postoperative white matter injury or focal infarction (mixed-model analysis, all F > 0.12). CONCLUSIONS: Postoperative indices of cerebral oxygenation and cerebral autoregulation are not independent predictors of new ischemic brain injury in infants with critical congenital heart disease. Further exploration of the complex interplay among low regional cerebral oxygen saturation, low cardiac output syndrome, and heart defect is required to identify potential biomarkers enabling early intervention for ischemic brain injury.

The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice.

Subcortical white matter infarction causes ischemic demyelination and loss of brain functions, as the result of disturbances of the blood flow. Although angiogenesis is one of the recovery processes after cerebral infarction, the dynamics of revascularization after white matter infarction still remains unclear. We induced white matter infarction in the internal capsule of Flk1-GFP::Flt1-tdsRed double transgenic mice by injection of endothelin-1 (ET-1), a vasoconstrictor peptide, together with N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and followed the changes in Flk1 and Flt1 expression in the vascular system in the infarct area. Reduction of Flt1-tdsRed-positive blood vessels 1 day after the injection and increase of Flk1-GFP-strongly-positive blood vessels 3 days after the injection were apparent. PDGFRß-strongly-positive (PDGFRß+) cells appeared in the infarct area 3 days after the injection and increased their number thereafter. Three days after the injection, most of these cells were in close contact with Flk1-GFP-positive endothelial cells, indicating these cells are bona fide pericytes. Seven days after the injection, the number of PDGFRß+ cells increased dramatically, and the vast majority of these cells were not in close contact with Flk1-GFP-positive endothelial cells. Taken together, our results suggest revascularization begins early after the ischemic insult, and the emerging pericytes first ensheath blood vessels and then produce fibroblast-like cells not directly associated with blood vessels.

Clinical and imaging features of vertebrobasilar dolichoectasia combined with posterior circulation infarction: A retrospective case series study.

This study aims to analyze the clinical and imaging features of vertebrobasilar dolichoectasia (VBD) combined with posterior circulation infarction, and to explore risk factors for the occurrence of posterior circulation infarction in VBD patients.VBD patients were divided into 2 groups, according to the results of the imaging examination: posterior circulation infarction group and nonposterior circulation infarction group. The demographics, vascular risk factors, imaging, and other clinical data of the VBD patients were collected and retrospectively compared, and the risk factors for the occurrence of posterior circulation infarction in VBD patients were analyzed. The relationship between imaging features of the VBD blood supply artery and the infarct site was also analyzed.A total of 56 VBD patients were included into the analysis. Among these patients, 26 patients had posterior circulation infarction. Infarction occurred in the blood supply area of the posterior cerebral artery in 14 patients. The difference in the height of the basilar artery bifurcation between patients with vertebrobasilar artery blood supply area infarction and patients with posterior cerebral artery supply area infarction was statistically significant. Hypertension and posterior circulation intracranial atherosclerosis were the risk factors for posterior circulation infarction in VBD patients.Elevated basilar artery bifurcation is a risk factor for infarction in the posterior cerebral artery supply area in VBD patients. Posterior circulation infarction in VBD may be the comprehensive result of multiple factors, such as congenital defects of the basilar artery wall, hypertension, and atherosclerotic lesions.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Effects of Increased Intracranial Pressure Gradient on Cerebral Venous Infarction in Rabbits.

BACKGROUND: Cerebral venous infarction (CVI) is a rare vascular disease most commonly caused by cerebral venous thrombosis that leads to hemorrhage or infarct formation. A rabbit model of CVI was established by placing a recoverable epidural sacculus to research effects of increased pressure on CVI. METHODS: Rabbits were randomly divided into the following groups: A, CVI; B, 0.2-mL epidural sacculus placed on the basis of CVI; C, 0.4-mL epidural sacculus; D, 0.6-mL epidural sacculus; E, sham operation. Two sacculus-release groups were then added, 8 hours (group F) and 24 hours (group G), on the basis of group D. Brain water content, extent of cerebral infarction, hemorheology indexes, D dimer, and fibrinogen were observed at 8, 24, and 48 hours after surgery. RESULTS: Brain water content was higher in groups A-D compared with group E with the exception of the 24-hour A group. Brain water content was significantly lower in sacculus-release groups compared with the 48-hour D group. Extent of cerebral infarction in group D was significantly higher at 24 and 48 hours compared with groups A and E. Extent of cerebral infarction in sacculus-release groups was significantly lower compared with group D at 48 hours. Hemorheology indexes and fibrinogen were significantly higher in group D compared with groups A and E at corresponding time points and increased with increasing intracranial pressure. CONCLUSIONS: In the rabbit model of CVI, degree of brain edema, extent of cerebral infarction, hemorheology indexes, and fibrinogen increased as intracranial pressure gradient increased, which may promote formation of a hypercoagulable state. Early removal of intracranial hypertension reduced degree of edema and extent of cerebral infarction in rabbits.