Although early brain injury (EBI) is recognized as a critical step following subarachnoid hemorrhage (SAH), its pathophysiology and underlying mechanisms remain poorly understood. Herein, we ...investigated the role of cerebral circulation in the acute phase using patient data and a mouse SAH model and evaluated its regulation via the sympathetic nervous system.
The cerebral circulation time and neurological outcomes in the human body were retrospectively examined in 34 SAH cases with ruptured anterior circulation aneurysms and 85 cases with unruptured anterior circulation cerebral aneurysms at Kanazawa University Hospital from January 2016 to December 2021. In a mouse study, a SAH model was created via endovascular perforation, and India-ink angiography was performed over time. Additionally, bilateral superior cervical ganglionectomy was performed immediately before surgery, and neurological scores and brain water content were evaluated after SAH.
Cerebral circulation time was prolonged in the acute phase of SAH compared with that in the unruptured cerebral aneurysm group, especially in those with electrocardiographic changes. Furthermore, it was more prolonged in the poor prognosis group (modified Rankin Scale scores 3-6) than in the good prognosis group (modified Rankin Scale scores 0-2) at discharge. In mice, cerebral perfusion was significantly reduced at 1 and 3 hours after SAH and recovered at 6 hours. superior cervical ganglionectomy improved cerebral perfusion without altering the diameter of the middle cerebral artery at 1 hour and improved neurological outcomes at 48 hours after SAH. Consistently, brain edema, quantified by brain water content, was improved by superior cervical ganglionectomy 24 hours after SAH.
Sympathetic hyperactivity may play a critical role in the development of EBI by impairing cerebral microcirculation and edema in the acute phase following SAH.
Hemorrhage from a recurrent aneurysm is a major concern after coiling for intracranial aneurysms. We aimed to identify aneurysm recurrence patterns associated with hemorrhage. We investigated ...radiological data of patients who underwent coiling for intracranial aneurysms in 2008-2016 and were followed-up for at least 6 months. Aneurysm recurrence patterns were classified as: type â , enlargement of aneurysm neck; type II, recurrent cavity within the coil mass; type â¢, recurrent cavity along the aneurysm wall; and type â£, formation of a daughter sac. We evaluated the incidence of various recurrence patterns with or without hemorrhage. Of the 173 aneurysms included in the study (mean follow-up period, 32 months; range, 6-99 months), 22 (13%) recurred and required re-treatment. The recurrence patterns included type â , II, â¢, and ⣠in 7 (4%), 4 (2%), 9 (5%), and 2 (1%) cases, respectively. Most of the type â , II, and ⢠recurrences occurred within 1 year, and type ⣠occurred at 7 years after coiling. Three aneurysms exhibited hemorrhage, one with type ⢠and two with type ⣠pattern. The two aneurysms with type ⣠recurrence initially occurred as type â ; however, the recurrent neck enlarged gradually, resulting in new sac formation. We recommend prompt re-treatment for aneurysms recurring with type ⢠or ⣠patterns, as such patterns were associated with hemorrhage. Furthermore, we need a special care to type â recurrence with enlargement of recurrent neck because this specific pattern may develop to type â£.
Purpose
A previous study on computational fluid dynamics reported that a high pressure difference (PD) at the surface of a coil mass is a strong predictor of aneurysm recurrence after coil ...embolization. PD was calculated using a virtual post-coiling model (VM), created by manually cutting the aneurysm by the flat plane from an anatomic model created with pre-coil embolization data; however, its credibility has not been fully evaluated. This study aims to clarify whether PD values calculated using the post-coiling model, which reflects the actual coil plane, are a strong predictor of aneurysm recurrence.
Methods
Fifty internal carotid artery aneurysms treated with endovascular coil embolization were analyzed (7 recanalized, 43 stable). We created and subjected two post-coiling models, namely, VM and the real post-coiling model (RM), constructed from the post-coil embolization data. The relationship between PD and aneurysm recurrence was examined using these models. PD and its constituent three parameters were compared between VM and RM.
Results
PD values calculated using RM showed significantly higher aneurysm recurrence in recurrence group than stable group (
p
< 0.001), and multivariate analysis showed that PD in RM (
p
= 0.02; odds ratio, 36.24) was significantly associated with aneurysm recurrence. The receiver operating characteristic analysis revealed that PD values accurately predicted aneurysm recurrence (area under the curve, 0.977; cutoff value, 3.08; sensitivity, 100%; specificity, 97.7%). All four parameters showed a significant correlation with VM and RM (
p
< 0.001).
Conclusion
Use of PD to predict recurrence after coil embolization can be clinically relevant.
Background
Although bleb formation increases the risk of rupture of intracranial aneurysms, previous computational fluid dynamic (CFD) studies have been unable to identify robust causative ...hemodynamic factors, due to the morphological differences of prebleb aneurysm models and a small number of aneurysms with de novo bleb formation. This study investigated the influences of differences in the aneurysm-models and identify causative hemodynamic factors for de novo bleb formation.
Materials and methods
CFD analysis was conducted on three aneurysm models, actual prebleb, postbleb, and virtual prebleb models of two unruptured aneurysms with de novo bleb formation. A new multipoint method was introduced in this study. We evenly distributed points with a 0.5-mm distance on the aneurysm surface of the actual prebleb models (146 and 152 points in the individual aneurysm, respectively), and we statistically compared hemodynamics at the points in the areas with and without bleb formation (19 and 279 points, respectively).
Results
Visually, blebs formed on an aneurysm surface area with similar hemodynamic characteristics in the actual and virtual prebleb models. Statistical analysis using the multipoint method revealed that the de novo bleb formation area was significantly correlated with high pressure (
p
< 0.001), low wall shear stress (WSS) (
p
< 0.001), and the center of divergent WSS vectors (
p
= 0.025).
Conclusions
De novo bleb formation in intracranial aneurysms may occur in areas associated with the combination of high pressure, low WSS, and the center of divergent WSS vectors. The multipoint method is useful for statistical analysis of hemodynamics in a limited number of aneurysms.
Although the inflow hemodynamics of cerebral aneurysms are key factors in their rupture and recurrence after endovascular treatments, the most available method for inflow hemodynamics evaluation ...remains unestablished. We compared the efficacy of inflow hemodynamics evaluation using computational fluid dynamics (CFD) analysis and that using four-dimensional (4D) flow magnetic resonance imaging (MRI).
In 23 unruptured cerebral aneurysms, the inflow hemodynamics was evaluated using both CFD and 4D flow MRI. The evaluated parameters included visually classified inflow jet patterns, the inflow rate ratio (the ratio of the inflow rate at the aneurysmal orifice to the flow rate in the proximal parent artery), and the velocity ratio (the ratio of the inflow velocity to the velocity in the proximal parent artery). The Shapiro-Wilk test was used to assess the normality of variable data, and logarithmic transformation was performed for variables with non-normal distributions. Data analysis was performed using Pearson correlation analyses and the chi-square test.
There was a significant correlation between inflow jet patterns evaluated by CFD and 4D flow MRI (p = 0.008). Moreover, there was a strong correlation between the inflow rate ratios evaluated by CFD and 4D flow MRI (r = 0.801; p <0.001). Furthermore, there was a moderate correlation between the velocity ratios measured by CFD and 4D flow MRI (r = 0.559; p = 0.008).
Inflow hemodynamics evaluated by CFD analysis and 4D flow MRI showed good correlations in inflow jet pattern, inflow rate ratio, and velocity ratio.
Common femoral artery (CFA) puncture is performed for endovascular treatment. However, we sometimes experience branch punctures when the CFA bifurcation level is high. In this study, we examined the ...frequency of high CFA bifurcation level and related factors.
The CFA bifurcation level was identified in 100 patients, who underwent cerebral angiography or endovascular treatment by femoral artery (FA) puncture, on 191 sides. The height of the CFA bifurcation level was classified into three groups: normal, high, and very high. Age, gender, left–right difference, height, weight, body mass index, and comorbidities, including hypertension, dyslipidemia, and diabetes, were examined to determine the factors associated with high CFA bifurcation level.
The normal, high, and very high groups were on 142, 35, and 14 sides, respectively. The high and very high groups, which were defined as high CFA bifurcation levels, accounted for 25% of all patients. Multivariate analysis revealed that the proportion of patients with high CFA bifurcation levels was higher in the elderly (p = 0.009) and those with a history of diabetes (p = 0.042).
Approximately one-fourth of all patients undergoing cerebral angiography or endovascular treatment by FA puncture had high CFA bifurcation levels, which had a significant association with old age and history of diabetes. For urgent treatment, FA puncture might be performed at a higher level below the inguinal ligament if patients are elderly of those with a history of diabetes.
Disruption of the blood‐brain barrier (BBB) following cerebral ischemia is closely related to the infiltration of peripheral cells into the brain, progression of lesion formation, and clinical ...exacerbation. However, the mechanism that regulates BBB integrity, especially after permanent ischemia, remains unclear. Here, we present evidence that astrocytic N‐myc downstream‐regulated gene 2 (NDRG2), a differentiation‐ and stress‐associated molecule, may function as a modulator of BBB permeability following ischemic stroke, using a mouse model of permanent cerebral ischemia. Immunohistological analysis showed that the expression of NDRG2 increases dominantly in astrocytes following permanent middle cerebral artery occlusion (MCAO). Genetic deletion of Ndrg2 exhibited enhanced levels of infarct volume and accumulation of immune cells into the ipsilateral brain hemisphere following ischemia. Extravasation of serum proteins including fibrinogen and immunoglobulin, after MCAO, was enhanced at the ischemic core and perivascular region of the peri‐infarct area in the ipsilateral cortex of Ndrg2‐deficient mice. Furthermore, the expression of matrix metalloproteinases (MMPs) after MCAO markedly increased in Ndrg2−/− mice. In culture, expression and secretion of MMP‐3 was increased in Ndrg2−/− astrocytes, and this increase was reversed by adenovirus‐mediated re‐expression of NDRG2. These findings suggest that NDRG2, expressed in astrocytes, may play a critical role in the regulation of BBB permeability and immune cell infiltration through the modulation of MMP expression following cerebral ischemia.
Main Points
Ndrg2 deficiency causes enhanced BBB permeability following brain ischemia.
NDRG2 negatively regulates MMP‐3 expression cell‐autonomously and MMP‐9 expression non‐cell‐autonomously.
Astrocytic NDRG2 plays protective roles in brain ischemia.
Meningiomas and unruptured cerebral aneurysms (UCAs) rarely coexist. However, the treatment strategy remains to be fully elucidated. This report is a first report that UCA related to the tumor feeder ...intraoperatively ruptured when the meningioma was resected.
Herein, we present a case of meningioma coexisting with contralateral UCA related to a tumor feeder. Immediately after the meningioma was resected, intraoperative acute brain swelling due to rupture of the contralateral aneurysm appeared. The swollen brain protruding into the epidural space was resected, following contralateral ruptured aneurysm was performed by endovascular surgery. Intensive neurological treatment was administered and the patient gradually recovered.
This report highlights the possibility of intraoperative UCA rupture related to the tumor feeder when the meningioma is resected.
Large or giant paraclinoid aneurysms typically have good indication for flow diverter (FD) treatment. Here, we report a very rare case of a patient with an unruptured supraclinoid large aneurysm who ...underwent FD deployment with coil embolisation that resulted in delayed visual field defect (VFD) and hydrocephalus. A 75-year-old woman with a large right supraclinoid aneurysm presented with severe hemianopia in the right eye. She underwent FD deployment with coil embolisation of the aneurysm. However, permanent left visual field loss occurred four months after surgery. Magnetic resonance imaging (MRI) showed severe oedema surrounding the aneurysm along the optic tract. Inflammation led to postoperative hydrocephalus, requiring ventriculoperitoneal shunt placement. To the best of our knowledge, this is the first report of both a delayed VFD and hydrocephalus following FD treatment. In cases of FD treatment with coil embolisation for large paraclinoid aneurysms, clinicians should keep in mind that postoperative visual impairment or/and hydrocephalus may occur.
Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (
,
) or its receptor (
) fail to nurture. Normal ...maternal behaviour is restored by peripheral oxcytocin replacement in
and
, but not
mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in
male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in
mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.
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