UNASSIGNED: Platelets prevent bleeding in a variety of inflammatory settings, the adhesion receptors and activation pathways involved being highly context-dependent and functionally redundant. In some situations, platelets recruited to inflammatory sites act independently of aggregation. The mechanisms underlying stable platelet adhesion in inflamed microvessels remain incompletely understood, in particular, whether and if so, how β1 and β3 integrins are involved.
UNASSIGNED: The impact of isolated or combined platelet deficiency in β1 and β3 integrins on inflammation-associated hemostasis was investigated in 3 models of acute inflammation: immune complex-based cutaneous reverse passive Arthus reaction, intranasal lipopolysaccharide-induced lung inflammation, and cerebral ischemia-reperfusion following transient (2-hour) occlusion of the transient middle cerebral artery.
UNASSIGNED: Mice with platelet-directed inactivation of Itgb1 (PF4Cre-β1-/-) displayed no bleeding in any of the inflammation models, while mice defective in platelet Itgb3 (PF4Cre-β3-/-) exhibited bleeding in all 3 models. Remarkably, the bleeding phenotype of PF4Cre-β3-/- mice was exacerbated in the reverse passive Arthus model by the concomitant deletion of β1 integrins, PF4Cre-β1-/-/β3-/- animals presenting increased bleeding. Intravital microscopy in reverse passive Arthus experiments highlighted a major defect in the adhesion of PF4Cre-β1-/-/β3-/- platelets to inflamed microvessels. Unlike PF4Cre-β1-/- and PF4Cre-β3-/- mice, PF4Cre-β1-/-/β3-/- animals developed early hemorrhagic transformation 6 hours after transient middle cerebral artery occlusion. PF4Cre-β1-/-/β3-/- mice displayed no more bleeding in lipopolysaccharide-induced lung inflammation than PF4Cre-β3-/- animals.
UNASSIGNED: Altogether, these results show that the requirement for and degree of functional redundancy between platelet β1 and β3 integrins in inflammation-associated hemostasis vary with the inflammatory situation.

Our study aimed to evaluate the postoperative outcome of patients with unruptured giant middle cerebral artery (MCA) aneurysm revealed by intracranial hypertension associated to midline brain shift. From 2012 to 2022, among the 954 patients treated by a microsurgical procedure for an intracranial aneurysm, our study included 9 consecutive patients with giant MCA aneurysm associated to intracranial hypertension with a midline brain shift. Deep hypothermic circulatory flow reduction (DHCFR) with vascular reconstruction was performed in 4 patients and cerebral revascularization with aneurysm trapping was the therapeutic strategy in 5 patients. Early (< 7 days) and long term clinical and radiological monitoring was done. Good functional outcome was considered as mRS score ≤ 2 at 3 months. The mean age at treatment was 44 yo (ranged from 17 to 70 yo). The mean maximal diameter of the aneurysm was 49 mm (ranged from 33 to 70 mm). The mean midline brain shift was 8.6 mm (ranged from 5 to 13 mm). Distal MCA territory hypoperfusion was noted in 6 patients. Diffuse postoperative cerebral edema occurred in the 9 patients with a mean delay of 59 h and conducted to a postoperative neurological deterioration in 7 of them. Postoperative death was noted in 3 patients. Among the 6 survivors, early postoperative decompressive hemicraniotomy was required in 4 patients. Good functional outcome was noted in 4 patients. Complete aneurysm occlusion was noted in each patient at last follow-up. We suggest to discuss a systematic decompressive hemicraniotomy at the end of the surgical procedure and/or a partial temporal lobe resection at its beginning to reduce the consequences of the edema reaction and to improve the postoperative outcome of this specific subgroup of patients. A better intraoperative assessment of the blood flow might also reduce the occurrence of the reperfusion syndrome.

UNASSIGNED: Traumatic middle cerebral artery (MCA) pseudoaneurysms following minor head trauma are rare.
UNASSIGNED: We report a case of a 76-year-old man who presented with a traumatic acute subdural hematoma and subarachnoid hemorrhage (SAH) from a ruptured distal right MCA pseudoaneurysm treated with evacuation of the hematoma, resection of the pseudoaneurysm, and an MCA-to-MCA bypass.
UNASSIGNED: Although traumatic pseudoaneurysms of the distal intracranial vessels are rare, patients with traumatic SAH would benefit from vascular imaging. Treatment of pseudoaneurysms of distal intracranial vessels may be treated with vessel occlusion or trapping/excision of aneurysm with revascularization.

Studies have shown cerebrovascular dysfunction in offspring with full-gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety-like behavioural changes seen with full-term exposure. To test this, rats were time-mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2-7), second trimester (GD8-14), third trimester (GD15-21) or full-term gestation (GD2-21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60-puffs/day (5 days/week) using either 5 or 30 watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23-38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3- and 6-month-old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full-term exposure (31-46%). Offspring also displayed changes in body composition, body mass, anxiety-like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety-like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid- to late-gestation in pregnancy, and both 5 W and 30 W exposure produce significant vascular dysfunction compared to Air. KEY POINTS: Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans. Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig-induced vascular impairment is not known. This study demonstrates Ecig exposure during mid- and late-gestation (i.e. second or third trimester) results in impaired endothelial cell-mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety-like behaviour in offspring. Maternal exposure prior to conception did not impact offspring\'s vascular or anxiety-like behavioural outcomes. Rodent models have been a reliable and useful predictor of inhalation-induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long-term harm to their offspring.

OBJECTIVE: Unruptured middle cerebral artery aneurysm (uMCAA) has traditionally been treated with open surgical clipping (SC). Endovascular treatments (EVTs) were designed to reduce surgical risks in these cases. Nevertheless, despite its potential benefits, many surgeons favor SC for uMCAA. This updated meta-analysis aimed to compare the safety, efficacy, and clinical outcomes of SC and EVT for uMCAA.
METHODS: The authors searched the Medline, Embase, and Cochrane Library databases according to the Cochrane and PRISMA guidelines. Eligible studies included those with ≥ 4 patients with uMCAA reporting comparative data of SC and EVT. The endpoints were the complete occlusion rate (Raymond class I and II), good clinical outcomes (modified Rankin Scale score ≤ 2 or Glasgow Outcome Scale score ≥ 4), procedure-related complications (further divided into major and minor), and mortality. The authors pooled OR with 95% CI values with a random-effects model. I2 statistics were used to assess heterogeneity, and sensitivity analysis was conducted to address high heterogeneity. Publication bias was assessed with funnel plot analysis and the Egger\'s test.
RESULTS: The analysis included data from 10 studies. Regarding the complete occlusion assessment, the comparative analysis revealed OR 0.17 (95% CI 0.08-0.40, p < 0.01), favoring SC. In terms of achieving good clinical outcomes, OR 0.44 (95% CI 0.20-0.97, p < 0.05) was determined, favoring SC. No differences regarding total procedure-related complications, major complications, or mortality were identified. However, a higher likelihood of minor complications was identified for EVT, with OR 4.68 (95% CI 2.01-10.92, p < 0.01).
CONCLUSIONS: This systematic review and meta-analysis identified a lower likelihood of complete occlusion at last follow-up and lower likelihood of good clinical outcomes in patients treated with EVT when compared with SC. Furthermore, a higher likelihood of minor complications was identified in patients who underwent EVT when compared with SC. The findings reinforce that, based on the currently available data, SC should be considered the primary approach for treating uMCAA. However, EVT is an evolving approach, and this study\'s findings represent a synthesis of observational studies. Randomized trials are warranted to elucidate which approach should be the mainstay for uMCAA and to identify the nuances that determine whether SC or EVT is more or less indicated for addressing uMCAA with consideration of the individuality of each patient and aneurysm.

OBJECTIVE: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time.
METHODS: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms.
RESULTS: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03).
CONCLUSIONS: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

Endothelial dysfunction is a predictor for cardiovascular disease. Pre-clinical data suggest longstanding cardiovascular and cerebrovascular dysfunction occurs in offspring with perinatal electronic cigarette (Ecig) exposure. Further, direct use of Ecigs increases reactive oxygen species and impairs cerebrovascular function, but the combined effect of direct use in offspring with a history of perinatal exposure (i.e. double-hit condition) is not known. We tested the hypothesis that offspring with double-hit Ecig exposure will lead to greater cerebrovascular and neurocognitive dysfunction compared to in utero exposure only. Male and female offspring were obtained from time-mated Sprague Dawley female rats exposed to air (n=5 dams) or Ecig exposed (n=5 dams) and studied at either 3- or 6-months after birth. Ecig exposure for double-hit offspring began at 1-month before the timepoints and lasted 4-weeks (5-days/week with 90-min exposure/day). We found double-hit offspring (Ecig:Ecig=exposure dam:offspring) sustained further blunted MCA reactivity, increased severity of neuronal damage, and increased interactions of astrocytes and endothelial cells compared to offspring with maternal (Ecig:Air) or direct (Air:Ecig) exposure only. Circulating extracellular vesicles (EVs) were increased, while SIRT1 was decreased, in all Ecig exposed groups compared to controls (Air:Air), with Ecig:Ecig group showing the greatest respective change for each. Electron paramagnetic resonance spectroscopy revealed oxidative stress was the highest in the plasma of Ecig:Ecig group(p<0.05) than the other groups. These data show that a double-hit exposure in adolescent or adult offspring results in a greater decline in cerebrovascular function, biomarkers of neuronal dysfunction, and increased circulation of EVs compared to a single-hit exposure.

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Face masks are crucial parts of personal protective equipment (PPE) to reduce the risk of respiratory infections. The COVID-19 outbreak has increased healthcare workers’ use of face masks. This study aimed to evaluate changes in cerebrovascular response among healthcare workers using surgical and N95 respirator masks. 

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90 healthcare workers: 30 wearing surgical masks, 30 wearing N95 respirators, and 30 without masks were included. After two-hour of face mask use, the baseline mean flow velocity (MFV) and the mean breath-holding index (BHI) of the bilateral middle cerebral arteries (MCAs) were evaluated with transcranial Doppler ultrasound. The presence of de-novo headache was recorded. BHI values ​​below 0.69 were evaluated as a sign of impaired cerebrovascular reactivity (CVR). 

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The rate of de-novo headache was significantly higher in the N95 respirator mask group (p = 0.004). Compared to the control and surgical mask groups, the N95 respirator mask group had significantly lower values of the baseline MFV of the right MCA (p = 0.003 and p = 0.021, respectively) and mean BHI (p = 0.003 and p = 0.012, respectively). Still, only one N95 respirator mask user had a mean BHI value below 0.69.

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Surgical masks did not signi­fi­cantly affect cerebral hemodynamics. Although N95 respirator mask use significantly decreased BHI values, the CVR is still within normal limits, and the development of de-novo headache is not directly associated with low CVR. 

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Az arcmaszkok a légzőszervi fertőzések kockázatának csökkentésére alkalmazott személyes védőfelszerelés (PPE) elengedhetetlen részét képezik. A Covid-19-járvány hatására fokozódott az egészségügyi dolgozók arcmaszkhasználata. Tanulmányunk célja az volt, hogy értékeljük a sebészeti és az N95 respirátor maszkot viselő egészségügyi dolgozók körében bekövetkező cerebrovascularis válasz változásait.

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Összesen 90 egészségügyi dolgozót vontunk be a tanulmányba: 30-an sebészeti maszkot és 30-an N95 respirátor maszkot viseltek, míg 30-an nem viseltek maszkot. Kétórás maszkhasználat után trans­cranialis Doppler-ultrahanggal értékeltük a bilaterális középagyi artériák (MCA) átlagos áramlási sebességét (MFV) és átlagos légzéstartási indexét (BHI). Rögzítettük a de novo fejfájás jelenlétét. A 0,69 alatti BHI-értékeket a károsodott cerebrovascularis reaktivitás (CVR) jelének tekintettük. 

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A de novo fejfájás előfor­dulási aránya szignifikánsan magasabb volt az N95 légzőmaszkot viselő csoportban (p = 0,004). Az N95 légzőmaszkot viselő csoportban a jobb MCA átlagos áramlási sebességének kiindulási értéke (p = 0,003, illetve p = 0,021) és az átlagos BHI-értékek (p = 0,003 és p = 0,012) szignifikánsan alacsonyabbak voltak a kontroll- és a sebészeti maszkot viselő csoportok értékeihez képest. Mindazonáltal, csak egy N95 légzőmaszkot viselő személy esetében volt az átlagos BHI-érték 0,69 alatt.

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A sebészeti maszk hasz­nálata nem befolyásolta szignifikánsan a ce­rebralis hemodinamikát. Habár az N95 lég­zőmaszk használata szignifikánsan csökkentette a BHI-értékeket, a CVR-értékek továbbra is a normáltartományban voltak, és a de novo fejfájás kialakulása nem volt közvetlen összefüggésben az alacsony CVR-rel.

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Transient ischemic attack (TIA) is an early warning sign of stroke and death, necessitating suitable animal models due to the associated clinical diagnostic challenges. In this study, we developed a TIA model using flexible spatially targeted photothrombosis combined with real-time blood flow imaging feedback. By modulating the excitation light using wavefront technology, we precisely created a square light spot (50 × 250 µm), targeted at the distal middle cerebral artery (dMCA). The use of laser speckle contrast imaging (LSCI) provided real-time feedback on the ischemia, while the excitation light was ceased upon reaching complete occlusion. Our results demonstrated that the photothrombus formed in the dMCA and spontaneously recanalized within 10 min (416.8 ± 96.4 s), with no sensorimotor deficits or infarction 24 h post-TIA. During the acute phase, ischemic spreading depression occurred in the ipsilateral dorsal cortex, leading to more severe ischemia and collateral circulation establishment synchronized with the onset of dMCA narrowing. Post-reperfusion, the thrombi were primarily in the sensorimotor and visual cortex, disappearing within 24 h. The blood flow changes in the dMCA were more indicative of cortical ischemic conditions than diameter changes. Our method successfully establishes a photochemical TIA model based on the dMCA, allowing for the dynamic observation and control of thrombus formation and recanalization and enabling real-time monitoring of the impacts on cerebral blood flow during the acute phase of TIA.