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Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke. Key words: angiogenesis, endothelial cells, hypoxia, NF-E2-related factor 2, vascular endothelial growth factor. Resume: L'accident vasculaire cerebral (AVC) ischemique est une condition pathologique cerebrovascular majeure qui resulte d'une reduction locale transitoire ou permanente du flux sanguin dans le cerveau. L'angiogenese joue un role important dans la reparation microvasculaire cerebrale a la suite de l'AVC ischemique. Cette etude visait a examiner l'effet de facteur Nrf2 ([much less than] NF-E2-related factor 2 [much greater than]) sur l'angiogenese des cellules endotheliales microvasculaires cerebrales de souris bEnd.3 dans un environnement hypoxique. Les auteurs ont trouve que l'expression de Nrf2 etait temporairement accrue chez les cellules bEnd.3 soumises a l'hypoxie. Le knockdown de Nrf2 inhibait la proliferation et la migration cellulaires, de meme que la formation de tube endothelial par les cellules bEnd.3 soumises a l'hypoxie. Parallelement, les voies de signalisation du facteur de croissance vasculaire endothelial et de la PI3K/Akt ont ete identifiees comme cibles regulees par Nrf2 chez les cellules bEnd.3 en hypoxie. Il appert que le silen[zeta]age de Nrf2 regulait a la baisse les niveaux d'expression de la NAD(P)H : quinine oxydoreductase-1, du facteur de croissance vasculaire endothelial, de p-Akt et de l'heme-oxygenase-1 dans les cellules bEnd.3 en hypoxie. Les donnees suggeraient que l'hypoxie induisait une elevation transitoire de Nrf2 qui joue un role cle dans la micro-angiogenese cerebrale, et que Nrf2 regulait la proliferation, la migration et la formation de tube endothelial vraisemblablement par l'intermediaire de la voie de signalisation PI3K/Akt chez les cellules bEnd.3 en hypoxie. L'etude des auteurs fournit une preuve de concept de la modulation de Nrf2 qui fait pencher la balance en faveur de l'angiogenese, constituant une strategie therapeutique dans l'hypoxie ou les conditions ischemiques comme l'AVC. [Traduit par la Redaction] Mots-cles: angiogenese, cellules endotheliales, hypoxie, Nrf2, facteur de croissance vasculaire endothelial., Introduction Stroke is one of the leading causes of death and serious long-term disability worldwide (Towfighi and Saver 2011). Ischemic stroke, resulting from focal cerebral ischemia due to occlusion of [...]

Background: Delayed post-hypoxic leukoencephalopathy (DPHL) is characterized by a biphasic clinical course, with complete recovery from coma to a fully conscious state lasting one to four weeks (lucid interval), followed by abrupt neurological deterioration as an indirect consequence of hypoxic events like carbon monoxide poisoning and narcotic drug overdose. To our best knowledge, there are no documented cases in literature of choreoathetosis and dementia following poppy-induced DPHL with 14-3-3 protein in cerebrospinal fluid (CSF)., Case Presentation: We report the case of a 70-year-old female who underwent cardiopulmonary resuscitation (CPR) due to overdose of homemade refined opium poppy paste two weeks prior to presentation. She presented a progressive cognitive decline, along with the development of apraxia and choreic movement affecting her tongue and bilateral upper and lower extremities. During the symptomatic phase, brain magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals mostly in central frontal, temporal, and parieto-occipital lobes in the diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences which are the characteristic findings of DPHL. CSF routine analysis, as well as toxicology screening, autoimmune and paraneoplastic encephalitis panels were negative, but the presence of 14-3-3 protein in the CSF was detected. With steroid therapy, hyperbaric oxygen therapy and symptomatic treatment, she experienced gradual improvement in cognition, motivation, and psychomotor function., Conclusion: DPHL represents a distinct form of encephalopathy characterized by unique clinical course and imaging features. It is the first report of DPHL with positive 14-3-3 protein in CSF. The potential of 14-3-3 protein as a biomarker for diagnosing DPHL and its ability to predict disease severity and prognosis warrants further research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Clinical Impact: Digital subtraction angiography (DSA) has traditionally been considered an effective method for visualizing carotid free-floating thrombus (CFFT), but it falls short in providing detailed structures of the lumen and the composition of thrombi, making it challenging to determine the etiology. Intravascular optical coherence tomography (OCT) is a valuable adjunct to DSA that can precisely evaluate the characteristics of the intrinsic vessel wall and accurately distinguish between red and white thrombus, providing clues to the etiology of CFFTs. Moreover, OCT not only precisely determined the scope of a floating thrombus but also provided guidance for decision-making in endovascular treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design., Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis., Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002)., Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer Y-XC declared a shared affiliation with the author PL to the handling editor at the time of the review., (Copyright © 2024 Yu, Shen, Zhang, Cui, Zha, Li, Li, Wang and Nan.)

Bilateral medial medullary infarction is a rare stroke subtype, and its diagnosis has become possible by brain magnetic resonance imaging. In this report, we describe a case in which acute bilateral medial medullary infarction accompanied by cerebral watershed infarction was clearly identified by diffusion-weighted imaging, and we discuss the mechanisms of bilateral medial medullary infarction accompanied by cerebral watershed infarction., (Copyright Journal of Radiology Case Reports.)

Rationale: Mild-to-moderate alcoholic cirrhosis of the liver is related to spontaneous intracerebral hemorrhage (ICH). In terms of spontaneous brainstem hemorrhage, pontine is considered as the most common site in contrast to medulla oblongata where the hemorrhage is rarely seen. This rare primary medullary hemorrhage has been attributed so far to vascular malformation (VM), anticoagulants, hypertension, hemorrhagic transformation, and other undetermined factors., Patient Concerns: Herein, we describe a 53-year-old patient with 35-year history of alcohol abuse was admitted for acute-onset isolated hemianesthesia on the right side. He was normotensive on admission. A neurological examination revealed isolated hemihypoaesthesia on the right side. He had no history of hypertension, and viral hepatitis, and nil use of anticoagulants., Diagnoses: Brain computed tomography (CT) image demonstrated hemorrhagic lesion in dorsal and medial medulla oblongata which was ruptured into the fourth ventricle. Brain magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) demonstrated no evidence of VM. The laboratory tests implied liver dysfunction, thrombocytopenia, and coagulation disorders. Abdominal ultrasound, and CT image showed a small, and nodular liver with splenomegaly, suggestive of moderate alcoholic cirrhosis., Interventions: Liver protection therapy and the management of coagulation disorders., Outcomes: After 14 days, he was discharged with mild hemianesthesia but with more improved parameters in laboratory tests. At the 6-month follow-up, brain MRI, MRA, and non-contrast MRI showed no significant findings except for a malacic lesion., Lessons: We conclude that the patient had alcoholic cirrhosis with coagulopathy, and this may have resulted in primary medullary hemorrhage. This is a first case to report alcoholic cirrhosis as etiology of primary medullary hemorrhage.

Background: Myoclonus is a clinical sign characterized by sudden, brief jerky, shock-like involuntary movements of a muscle or group of muscles. Dystonia is defined as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Cases of myoclonus or dystonia secondary to a structural lesion in the cerebellum have been reported. However, there has never been a reported case of combined myoclonus and dystonia secondary to a cerebellar lesion., Case Presentation: Herein, we report a 22-year-old female patient with sudden-onset myoclonic jerks, dystonic posture and mild ataxia in the right upper extremity. At age 19, she experienced sudden headache with vomiting. The neurological examination showed ataxia, myoclonus and dystonia in the right upper extremity. Brain images demonstrated a hemorrhage in the right cerebellar hemisphere secondary to a cavernous malformation. After resection of the hemorrhagic mass, headache with vomiting disappeared and ataxia improved, but myoclonus and dystonia persisted., Conclusions: It is the first report of combined focal myoclonus and dystonia secondary to a cerebellar lesion.