Hyperbaric Oxygen Mediated PI3K/Akt/mTOR Pathway in Inhibiting Delayed Cerebral Vasospasm after Subarachnoid Hemorrhage.

Delayed cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is a serious complication. This article aimed to explore the mechanism of hyperbaric oxygenation (HBO) inhibiting delayed CVS after SAH. The 60 SD rats were grouped: normal control group (NC), sham operation group (Sham), SAH Model (Model), and HBO treatment group. The SAH model was established by injecting blood twice into the cisterna magna (CM), and the neurological function of the rats were evaluated by modified Garcia scale. The plasma of the rats was collected at 1, 3, 6, and 9 days after HBO treatment. Plasma levels of PI3K/Akt/mTOR pathway-related proteins were detected by Western blot (WB). TUNEL method was used to observe the apoptosis rate of basilar artery (BA) endothelial cells (ECs). Hematoxylin-eosin staining (HE) staining was used to observe the inner diameter and the thickness of vessel wall of rat cerebral arteries. The relationship between mTOR and middle cerebral artery spasm was analyzed. As against the Model, the neurological function was visibly increased, the expressions of Bcl-2, PI3K, mTOR, and p-Akt/Akt protein in plasma were visibly increased, the expression of Bax protein was visibly decreased, and the degree of CVS was visibly reduced in the HBO group (all P < 0.05). The level of mTOR is negatively correlated with the degree of CVS after SAH, and HBO can inhibit the occurrence of delayed CVS.

Impact of post-thrombectomy isolated subarachnoid hemorrhage on neurological outcomes in patients with anterior ischemic stroke - a retrospective single-center observational study.

PURPOSE: We aimed to investigate the impact of post-thrombectomy isolated subarachnoid hemorrhage (i-SAH) and other types of intracranial hemorrhage (o-ICH) on patient's neurological outcomes. METHODS: Stroke data from 2018 to 2022 in a tertiary care center were retrospectively analyzed. Patients with large vessel occlusion from ICA to M2 branch were included. Post-thrombectomy intracranial hemorrhages at 24 h were categorized with Heidelberg Bleeding Classification. Neurological impairment of patients was continuously assessed at admission, at 24 h, 48 h and 72 h, and at discharge. Predictors of i-SAH and o-ICH were assessed. RESULTS: 297 patients were included. i-SAH and o-ICH were found in 12.1% (36/297) and 11.4% (34/297) of patients. Overall, NIHSS of i-SAH patients at discharge were comparable to o-ICH patients (median 22 vs. 21, p = 0.889) and were significantly higher than in non-ICH patients (22 vs. 7, p < 0.001). i-SAH often resulted in abrupt deterioration of patient's neurological symptoms at 24 h after thrombectomy. Compared to non-ICH patients, the occurrence of i-SAH was frequently associated with worse neurological outcome at discharge (median NIHSS increase of 4 vs. decrease of 4, p < 0.001) and higher in-hospital mortality (41.7% vs. 23.8%, p = 0.022). Regardless of successful reperfusion (TICI 2b/3), the beneficial impact of thrombectomy appeared to be outweighed by the adverse effect of i-SAH. Incomplete reperfusion and shorter time from symptom onset to admission were associated with higher probability of i-SAH, whereas longer procedure time and lower baseline ASPECTS were predictive for o-ICH occurrence. CONCLUSION: Post-thrombectomy isolated subarachnoid hemorrhage is a common complication with significant negative impact on neurological outcome.

Transcranial Doppler in the Detection of Cerebral Vasospasm After Subarachnoid Hemorrhage.

Background Transcranial Doppler (TCD) is a simple, noninvasive, nonionizing, portable technique but not widely practiced to detect cerebral vasospasm after subarachnoid hemorrhage (SAH). Objective The aim of this study was to assess the performance of TCD in the detection of cerebral vasospasm in patients with SAH considering CT angiography (CTA) as a gold standard. Methods and material This cross-sectional study included 50 patients with acute SAH admitted to the National Institute of Neurosciences & Hospital (NINS & H), Dhaka, Bangladesh, from February to June 2021. The neurological status, severity of SAH, and initial CT findings were recorded. All patients were screened for cerebral vasospasm with TCD on the 4th, 7th, 10th, and 14th days after the event. Screening of cerebral vasospasm by CTA was done on the 14th day of the event or earlier if TCD suggested vasospasm. Results The mean age of the participants was 51.4 ±13.4 years (mean ± SD), and females were predominant (N=29, 58%). CTA detected cerebral vasospasm in 18 (36%) participants, but TCD could detect it in only 13 (26%) cases. Among the participants who had no vasospasm by CTA, all but one were also found to have no vasospasm by TCD. The agreement between TCD and CTA in detecting cerebral vasospasm was significant (p<0.001, κ=0.726). TCD shows good specificity (96.9%) and positive predictive value (92.8%), but sensitivity (72.2%) and negative predictive value (81.6%) were comparatively lower. Overall, the diagnostic accuracy of TCD in detecting cerebral vasospasm was 88%. Conclusions Although compared to CTA, TCD is a highly specific but less sensitive tool in detecting vasospasm, TCD remains a reliable screening tool for detecting vasospasm following SAH.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Injection of Collagen Binding Domain-Brain Derived Neurotrophic Factor Promotes SIRT1 Expression: Improving Neuroinflammation in Experimental Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease, often leading to neuroinflammation and neuronal damage. Activation of the Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is closely associated with post-SAH neuroinflammation, while activation of Nicotinamide Adenine Dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1) has neuroprotective effects. This study aimed to investigate the impact of injectable Collagen Binding Domain-Brain Derived Neurotrophic Factor (CBD-BDNF) on neuroinflammation and neuronal damage following SAH. METHODS: After establishing the SAH model, experimental animals were divided into three groups: sham surgery group (Sham), SAH group, and SAH+neuroregenerative scaffold (CBD-BDNF treatment) group. Behavioral performance was evaluated using neurofunctional deficit, beam balance, and Y-maze tests. Expression of inflammatory factors and essential proteins was quantitatively analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) kits and immunoblotting. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) staining was used to assess cell apoptosis. To further investigate the mechanism of action of CBD-BDNF on SIRT1, the model animals were treated with EX527 (SIRT1 inhibitor) for comparative studies. RESULTS: Neurological deficit tests, CBD-BDNF improves functional outcomes after SAH. Compared to the SAH group, the SAH+neuroregenerative scaffold group showed significantly increased expression of SIRT1 protein and significantly decreased expression of NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC), and c-caspase-1. The inflammatory cytokines Interleukin-1 beta (IL-1ß), IL-6, and IL-18 levels also significantly decreased in the SAH+neuroregenerative scaffold group. Additionally, animals in the SAH+neuroregenerative scaffold group showed better neurofunctional recovery in neurofunctional deficit and beam balance tests. The number of apoptotic cells significantly decreased in the SAH+neuroregenerative scaffold group compared to the SAH group. However, when SIRT1 was inhibited with EX527, the aforementioned neuroprotective effects were reversed, indicating the involvement of CBD-BDNF through SIRT1 activation. CONCLUSION: This study demonstrates that injectable CBD-BDNF can significantly alleviate neuroinflammation and neuronal damage resulting from SAH by blocking NLRP3 inflammasome activation and promoting SIRT1 expression. These findings provide a new therapeutic strategy for neuroprotection after SAH and reveal the mechanism of action of CBD-BDNF as a potential therapeutic agent. Future research will further explore the long-term efficacy and safety of CBD-BDNF.

Prognostic value of platelet levels in patients with aneurysmal Subarachnoid Hemorrhage.

Pathophysiological processes following aneurysmal subarachnoid hemorrhage (aSAH) include upregulated underlying systemic inflammation, which is reflected by changes in different peripheral blood cells and their sub-populations. As inflammation is a crucial process that contributes to post-aSAH complications and clincal outcome, blood cell numbers and ratios in systemic circulation may predict the outcome and provide rapid and easy to quantify point of care biomarkers for these critically ill patients. To identify blood-derived cellular inflammatory parameters which allow a precise prediction of patient outcome after aSAH. In this single-center retrospective study, 19 whole blood-derived cellular inflammatory markers and clinical and demographic parameters for 101 aSAH patients were recorded within 24 h after aSAH. Clinical outcome was quantified with modified Rankin scale (mRS) on discharge. Proportional odds logistic regression (POLR) was used to model the patient outcome as the function of clinical parameters and inflammatory markers. The results were validated on a separate hold-out dataset (220 patients). The on-admission platelet count, mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) were found to be significant and predictive of patient outcome on discharge. Mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) predicted clinical outcome and may serve as easy to quantify point of care biomarker. The findings are potentially relevant for the management of aSAH.

Bifurcation dissecting aneurysm: tips and tricks to differentiate from saccular aneurysm.

Bifurcations are a common site for saccular aneurysms, but rarely can be a site for dissecting aneurysms. Identification of these aneurysms is extremely important because the management plan depends on it. We describe a rare case of a ruptured dissecting aneurysm at the right ICA bifurcation in a pre-teen child which posed a diagnostic dilemma but ultimately was successfully managed with flow diversion.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Potential biomarkers of ASD a target for future treatments: oxidative stress, chemokines, apoptotic, and methylation capacity.

OBJECTIVES: The study aimed to assess the effect of these biomarkers on a sample of children with autism spectrum disorder (ASD) to help in early diagnosis and intervention. METHODS: A total of 71 autistic patients and 65 normal controls were enrolled in this study. Their ages ranged from 5 to 11 years (mean ± SD 7.47 ± 3.81). Childhood Autism Rating Scale (CARS) was assessed for all patients and controls. Assessment of oxidative stress, monocyte chemoattractant protein-1, B-cell lymphoma 2, S-adenosylhomocysteine (SAH), and apelin was performed. RESULTS: Oxidative stress (oxidized low-density lipoprotein and malonaldehyde) increased while antioxidant paraoxonase (PON) decreased. Monocyte chemoattractant protein-1, B-cell lymphoma 2, and S-adenosylhomocysteine (SAH) were all elevated whereas, apelin was downregulated. CONCLUSIONS: It is important to note that many factors that may contribute to ASD including genetic factors. To open the door for novel treatment strategies, it is still necessary to precisely understand how oxidative stress, chemokines, apoptosis, and methylation capability affect the metabolism of people with ASD.

CDDO, an Anti-Inflammatory and Antioxidant Compound, Attenuates Vasospasm and Neuronal Cell Apoptosis in Rats Subjected to Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke caused by bleeding into the subarachnoid space. SAH is a medical emergency and requires prompt treatment to prevent complications such as seizures, stroke, or other brain damage. Treatment options may include surgery, medication, or a combination of both. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a compound with anti-inflammatory and antioxidant properties, is currently being investigated as a potential treatment for various diseases, including chronic kidney disease and pulmonary arterial hypertension. In this study, the effects of CDDO on rats subjected to SAH were evaluated. Male Sprague-Dawley rats were divided into four groups (n = 6/group): (1) control group, (2) SAH group, (3) SAH + low-dose CDDO (10 mg/kg injected into the subarachnoid space at 24 h after SAH) group, and (4) SAH + high-dose CDDO (20 mg/kg) group. CDDO improved SAH-induced poor neurological outcomes and reduced vasospasm in the basal artery following SAH. It also decreased the SAH-induced expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in both the cerebrospinal fluid and serum samples as determined by ELISA. A Western blot analysis confirmed an increase in the p-NF-κB protein level after SAH, but it was significantly decreased with CDDO intervention. Immunofluorescence staining highlighted the proliferation of microglia and astrocytes as well as apoptosis of the neuronal cells after SAH, and treatment with CDDO markedly reduced the proliferation of these glial cells and apoptosis of the neuronal cells. The early administration of CDDO after SAH may effectively mitigate neuronal apoptosis and vasospasm by suppressing inflammation.

ß-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice.

BACKGROUND: Both glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that ß-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. METHODS: The SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. RESULTS: Compared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. CONCLUSION: The study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

Comparative diagnostic efficacy of cranial CT, CTA, and DSA in subarachnoid hemorrhage management: A systematic review and meta-analysis.

INTRODUCTION: Subarachnoid hemorrhage (SAH) is a critical medical condition associated with high morbidity and mortality rates. Timely and accurate diagnosis is crucial for optimal patient outcomes. Cranial computed tomography (CT), computed tomography angiography (CTA), and digital subtraction angiography (DSA) are commonly used imaging modalities for diagnosing SAH, but their comparative diagnostic efficacy remains debated. METHODS: A systematic review and meta-analysis was conducted to evaluate the diagnostic performance of cranial CT, CTA, and DSA in identifying SAH. PubMed, Google scholar, Cochrane Library databases were searched for relevant studies published up to January 2024. Pooled sensitivity, specificity, and the summary receiver operating characteristic (SROC) curve were calculated using Review Manager 5.4. RESULTS: A total of 31 studies involving 10,287 patients were included in the analysis. The pooled sensitivity of cranial CT for detecting SAH was 94.7 % (95 % Confidence Interval, CI) with a specificity of 98.3 % (95 % CI). CTA demonstrated a pooled sensitivity of 94.1 % (95 % CI) and specificity of 93.4 % (95 % CI). DSA showed a pooled sensitivity of 87.7 % (95 % CI) and specificity of 95.8 % (95 % CI). The SROC curve demonstrated discriminatory ability for all modalities. CONCLUSION: Cranial CT, CTA, and DSA are valuable imaging modalities for diagnosing SAH, with high sensitivity and specificity. Cranial CT serves as an initial screening tool, while CTA offers superior sensitivity in detecting aneurysmal SAH. DSA remains essential in specific clinical scenarios. Further prospective studies are needed to validate these findings and refine diagnostic guidelines for SAH.

Structural basis for substrate recognition by a S-adenosylhomocysteine hydrolase Lpg2021 from Legionella pneumophila.

S-Adenosyl-l-homocysteine hydrolase (SAHH) is a crucial enzyme that governs S-adenosyl methionine (SAM)-dependent methylation reactions within cells and regulates the intracellular concentration of SAH. Legionella pneumophila, the causative pathogen of Legionnaires' disease, encodes Lpg2021, which is the first identified dimeric SAHH in bacteria and is a promising target for drug development. Here, we report the structure of Lpg2021 in its ligand-free state and in complexes with adenine (ADE), adenosine (ADO), and 3-Deazaneplanocin A (DZNep). X-ray crystallography, isothermal titration calorimetry (ITC), and molecular docking were used to elucidate the binding mechanisms of Lpg2021 to its substrates and inhibitors. Virtual screening was performed to identify potential Lpg2021 inhibitors. This study contributes a novel perspective to the understanding of SAHH evolution and establishes a structural framework for designing specific inhibitors targeting pathogenic Legionella pneumophila SAHH.

Cerebrospinal fluid volume as an early radiological factor for clinical course prediction after aneurysmal subarachnoid hemorrhage. A pilot study.

BACKGROUND: The pathological mechanisms following aneurysmal subarachnoid hemorrhage (SAH) are poorly understood. Limited clinical evidence exists on the association between cerebrospinal fluid (CSF) volume and the risk of delayed cerebral ischemia (DCI) or cerebral vasospasm (CV). In this study, we raised the hypothesis that the amount of CSF or its ratio to hemorrhage blood volume, as determined from non-contrast Computed Tomography (NCCT) images taken on admission, could be a significant predictor for CV and DCI. METHODS: The pilot study included a retrospective analysis of NCCT scans of 49 SAH patients taken shortly after an aneurysm rupture (33 males, 16 females, mean age 56.4 ± 15 years). The SynthStrip and Slicer3D software tools were used to extract radiological factors - CSF, brain, and hemorrhage volumes from the NCCT images. The "pure" CSF volume (VCSF) was estimated in the range of [-15, 15] Hounsfield units (HU). RESULTS: VCSF was negatively associated with the risk of CV occurrence (p = 0.0049) and DCI (p = 0.0069), but was not associated with patients' outcomes. The hemorrhage volume (VSAH) was positively associated with an unfavorable outcome (p = 0.0032) but was not associated with CV/DCI. The ratio VSAH/VCSF was positively associated with, both, DCI (p = 0.031) and unfavorable outcome (p = 0.002). The CSF volume normalized by the brain volume showed the highest characteristics for DCI prediction (AUC = 0.791, sensitivity = 0.80, specificity = 0.812) and CV prediction (AUC = 0.769, sensitivity = 0.812, specificity = 0.70). CONCLUSION: It was demonstrated that "pure" CSF volume retrieved from the initial NCCT images of SAH patients (including CV, Non-CV, DCI, Non-DCI groups) is a more significant predictor of DCI and CV compared to other routinely used radiological biomarkers. VCSF could be used to predict clinical course as well as to personalize the management of SAH patients. Larger multicenter clinical trials should be performed to test the added value of the proposed methodology.

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA ß-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a major cause of incapacity and death, imposing a significant economic burden globally. Additionally, SAH is the third most prevalent form of stroke. Semaglutide affects oxidative stress, inflammation, and mitochondrial biogenesis. Specifically, the potential neuroprotective effect of semaglutide in SAH and its underlying mechanism is unclear. Accordingly, the present research intended to explore the neuroprotective effect of semaglutide in SAH and its potential molecular mechanisms. METHODS: We constructed a C57BL/6 mouse model of SAH. The parameters assessed were neuronal ferroptosis, neuroinflammatory cytokine levels, reactive oxygen species (ROS) levels, glutathione (GSH) and malondialdehyde (MDA) levels, brain water content, and neurological score. RESULTS: The results showed that the activation of semaglutide significantly increased neurological scores, relieved cerebral edema, decreased the levels of inflammatory cytokine nuclear factor kappa B, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, MDA, and ROS, and increased the levels of GSH. Suppression of SIRT1 reversed these effects, indicating that semaglutide activated SIRT1 to reduce neuroinflammation, ferroptosis, and neuronal cell death after SAH. Thus, the activation of the Nrf2/HO-1 signaling pathway contributes to the neuroprotective properties of semaglutide. CONCLUSIONS: Semaglutide can improve murine neurological outcomes and reduce neuronal damage against neuroinflammation and ferroptosis.

Subarachnoid Hemorrhaging with Multiple Cerebral Artery Stenoses after Initiating Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: a Case Report.

We encountered a 64-year-old Japanese woman who developed subarachnoid hemorrhaging (SAH) with multiple cerebral artery stenoses during remission induction therapy for eosinophilic granulomatosis and polyangiitis (EGPA). The treatment involved intensified steroid pulse therapy and continued intravenous cyclophosphamide pulse therapy, which led to beneficial effects. Given the rarity of multiple EGPA-associated cerebral artery stenoses and SAH, it is crucial to differentiate them from other diseases. The mortality rate of EGPA complicated by intracranial hemorrhagic lesions, including SAH, is high. When headache is present at the onset of EGPA, the possibility of SAH must be considered.

Return to work after aneurysmal subarachnoid hemorrhage.

Introduction: Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often recover without severe physical or cognitive deficits. However, strikingly low levels of engagement in productive employment have also been reported in aSAH patients with good or excellent outcomes. Knowledge about return to work (RTW) after aSAH and predictors of no RTW remain limited and controversial. The study aimed to delineate the return to maximum work capacity up to 5 years after the ictus in a larger number of consecutive aSAH patients from the entire aSAH severity spectrum and to identify demographic and medical predictors of no RTW. Methods: Data were acquired from a prospective institutional database. We included all 500 aSAH survivors aged > 18 years who were treated between January 2012 and March 2018. In addition to gathering data on work status and the type of work at ictus, we retrieved demographical data and assessed aSAH severity based on the quantification of subarachnoid, intraventricular, and intraparenchymal blood (ICH), as well as the World Federation of Neurological Societies (WFNS) grade. We registered the mode of aneurysm repair (endovascular or surgical) and recorded complications such as vasospasm, newly acquired cerebral infarctions, and chronic hydrocephalus. Results: Furthermore, work status and the grade of fatigue at follow-up were registered. RTW was assessed among 299 patients who were employed at ictus. Among them, 63.2% were women, and their age was 51.3 ± 9.4 (20-71) years. Return to gainful employment was 51.2%, with complete RTW accounting for 32.4%. The independent predictors of no RTW at ictus were age, the WFNS grade 3, and active smoking. The strongest independent predictor was the presence of clinically significant fatigue, which increased the risk of not returning to work by 5-fold. The chance to return to gainful employment significantly increased with the individual's years of education prior to their hemorrhage. The mode of aneurysm repair was not relevant with regard to RTW. Patients in the WFNS grades 1-2 more often returned to work than those in the WFNS grades 3-5, but our results indicate that neurological motor deficits are linked closer to no RTW than aSAH severity per se. Conclusion: Fatigue needs to be addressed as an important element on the path to return to work integration.

Optimizing of a metal foam-assisted solar air heater performance: a thermo-hydraulic analysis of porous insert placement.

A numerical assessment of the heat transfer efficacy of a solar air heater (SAH) was carried out. The SAH is supplied with a porous metal foam layer to improve thermal mixing. Both the local thermal non-equilibrium (LTNE) and Darcy-extended Forchheimer (DEF) models were employed to forecast fluid and thermal transport within the partly filled SAH channel. The analysis was performed for various values of dimensionless foam layer lengths ( S = 0 - 1 ), pore densities ( ω = 10 - 40 PPI ), and Reynolds numbers ( R e = 4000 - 1 6 , 000 ) at a fixed value of layer thickness ( H f = 0.6 ). Based on the position of the porous layer, three distinct arrangements, marked as Case 1, Case 2, and Case 3, were explored. Regarding the parameters examined, the findings indicate a definite improvement in the average Nusselt number ( Nu ), but unfortunately, the friction factor also increases unfavorably. By reducing the length of the porous layer, a reasonable reduction in heat transfer rate and a significant decrease in pressure drop were noticed. The results showed about 26.64%, 48.73%, and 70.74% reductions in pressure drop by reducing the dimensionless foam length from 1 to 0.25, 0.5, and 0.75 respectively for ω = 10 at R e = 16 , 000 . On the other side, there are only about 11.05%, 23.11%, and 40.78% reductions in Nu . The exhaustive analysis of the thermal performance of SAH was conducted using the thermal performance factor (TPF), which considers the trade-off between the SAH channel's potential for improved heat transmission and its cost for pressure loss. The TPF may reach a maximum of 2.82 compared to the empty channel when the metal foam layer is inserted with S = 1 , for ω = 10 , and R e = 16 , 000 .

Trends in incidence and treatments of spontaneous subarachnoid hemorrhage- a 10 year hospital based study.

BACKGROUND: Improved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment. METHODS: The study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases. RESULTS: Endovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5-8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data. CONCLUSIONS: The incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.