LAMC1 attenuates neuronal apoptosis via FAK/PI3K/AKT signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The poor prognosis in patients with subarachnoid hemorrhage (SAH) is often attributed to neuronal apoptosis. Recent evidence suggests that Laminin subunit gamma 1 (LAMC1) is essential for cell survival and proliferation. However, the effects of LAMC1 on early brain injury after SAH and the underlying mechanisms are unknown. The current study aimed to reveal the anti-neuronal apoptotic effect and the potential mechanism of LAMC1 in the rat and in the in vitro SAH models. METHODS: The SAH model of Sprague-Dawley rats was established by endovascular perforation. Recombinant LAMC1 (rLAMC1) was administered intranasally 30 min after modeling. LAMC1 small interfering RNA (LAMC1 siRNA), focal adhesion kinase (FAK)-specific inhibitor Y15 and PI3K-specific inhibitor LY294002 were administered before SAH modeling to explore the neuroprotection mechanism of rLAMC1. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. Subsequently, SAH grades, neurobehavioral tests, brain water content, blood-brain barrier permeability, western blotting, immunofluorescence, TUNEL, and Fluoro-Jade C staining were performed. RESULTS: The expression of endogenous LAMC1 was markedly decreased after SAH, both in vitro and in vivo. rLAMC1 significantly reduced the brain water content and blood-brain barrier permeability, improved short- and long-term neurobehavior, and decreased neuronal apoptosis. Furthermore, rLAMC1 treatment significantly increased the expression of p-FAK, p-PI3K, p-AKT, Bcl-XL, and Bcl-2 and decreased the expression of Bax and cleaved caspase -3. Conversely, knockdown of endogenous LAMC1 aggravated the neurological impairment, suppressed the expression of Bcl-XL and Bcl-2, and upregulated the expression of Bax and cleaved caspase-3. Additionally, the administration of Y15 and LY294002 abolished the protective roles of rLAMC1. In vitro, rLAMC1 significantly reduced neuronal apoptosis, and the protective effects were also abolished by Y15 and LY294002. CONCLUSION: Exogenous LAMC1 treatment improved neurological deficits after SAH in rats, and attenuated neuronal apoptosis in both in vitro and in vivo SAH models, at least partially through the FAK/PI3K/AKT pathway.

Complications after endovascular treatment of large basilar trunk aneurysms.

BACKGROUND AND PURPOSE: Large basilar trunk aneurysms (BTAs) have a poor natural history if left untreated and always pose a significant challenge to endovascular treatment. The present study aimed to analyze the complications after endovascular treatment of large BTAs. METHODS: This was a retrospective, observational, cohort study. Between January 2015 and September 2022, 9116 patients with intracranial aneurysms came to our institution for management, of which 34 patients with 34 large (≥10 mm) BTAs were treated with endovascular treatment. Postprocedural complications, clinical, and angiographic outcomes were evaluated. RESULTS: All 34 patients (34 aneurysms) were successfully treated, of which 13 aneurysms were treated with flow diversion (FD), and 21 aneurysms were treated with stent-assisted coiling. Neurological complications occurred in 12 (35.3%) patients, with 7 (20.6%) deaths. Ischemic complications occurred in 10 (29.4%) patients, and 4 (11.8%) patients experienced hemorrhagic events. The incidences of favorable outcomes at discharge and last follow-up were 85.3% and 75.8%, respectively. The cumulative survival rates at 1 and 3 years were 86.5% and 71.4%, respectively. Unilateral vertebral artery sacrifice was associated with postprocedural complications (hazard ratio: 3.74, 95% confidence interval: 1.06-13.25, p = 0.041). The postprocedural complication rates were comparable between patients treated with FD and stent-assisted coiling (5/13, 38.5% vs. 7/21, 33.3%, p > 0.99). Angiography follow-up was available for 21 patients, and complete aneurysm occlusion was observed in 16/21 (76.2%) aneurysms. CONCLUSIONS: Endovascular treatment might be a feasible option for treating large BTAs. However, clinicians should be alerted to procedure-related complications, especially ischemic complications that cause disability or death. Unilateral vertebral artery sacrifice might be associated with postprocedural complications.

Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial.

BACKGROUND: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. METHODS: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. RESULTS: No significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). CONCLUSIONS: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

Low-profile visualized intraluminal support-within-Enterprise overlapping-stent technique versus flow diversion in the treatment of intracranial vertebrobasilar trunk dissecting aneurysms.

Background: It is necessary to explore the safety and efficacy of various endovascular treatment techniques in the treatment of patients with intracranial vertebrobasilar trunk dissecting aneurysms (VBTDAs). This study sought to compare the clinical and angiographic outcomes of patients with intracranial VBTDAs following low-profile visualized intraluminal support (LVIS)-within-Enterprise overlapping-stent technique with those of flow diversion (FD). Methods: This was a retrospective, observational, cohort study. Between January 2014 and March 2022, 9,147 patients with intracranial aneurysms were screened, and 91 patients with 95 VBTDAs who underwent LVIS-within-Enterprise overlapping-stent assisted-coiling technique or FD were included in the analysis. The primary outcome was the complete occlusion rate at the last angiographic follow-up. The secondary outcomes included adequate aneurysm occlusion, in-stent stenosis/thrombosis, general neurological complications, neurological complications within 30 days after the procedure, the mortality rate, and unfavorable outcomes. Results: Among the 91 included patients, 55 were treated with LVIS-within-Enterprise overlapping-stent technique (the LE group) and 36 were treated with FD (the FD group). The angiography results at the median follow-up time of 8 months showed complete occlusion rates of 90.0% and 60.9% for the LE and FD groups, respectively, with an adjusted odds ratio of 5.79 (95% CI: 1.35-24.85; P=0.01). Adequate aneurysm occlusion (P=0.98), in-stent stenosis/thrombosis (P=0.46), general neurological complications (P=0.22), neurological complications within 30 days after the procedure (P=0.63), mortality rate (P=0.31), and unfavorable outcomes (P=0.07) at the last clinical follow-up did not differ significantly between the 2 groups. Conclusions: A significantly higher complete occlusion rate for VBTDAs was found following LVIS-within-Enterprise overlapping-stent technique as compared with FD. The 2 treatment modalities have comparable adequate occlusion rates and safety profiles.

Outcomes after superficial temporal artery-middle cerebral artery anastomosis combined with multiple burr hole surgery and dural inversion synangiosis for moyamoya disease in adults.

Objective: Several forms of cerebral revascularization have been carried out to treat moyamoya disease, however, the existing methods are accompanied by a variety of complications. In this study, the authors aimed to evaluate the clinical and angiographic outcomes of a new surgical procedure: superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with multiple burr hole (MBH) surgery and dural inversion synangiosis for the treatment of moyamoya disease in adults. Methods: Patients treated for moyamoya disease from August 2019 to July 2021 were retrospectively reviewed. Clinical data, including perioperative complications and follow-up outcomes, were noted. Preoperative and postoperative angiograms were compared, and the diameters of the frontal branch of the superficial temporal artery (F-STA), the deep temporal artery (DTA), the distal superficial temporal artery (STA) before the bifurcation and the middle meningeal artery (MMA) were measured on preoperative and postoperative angiograms. Meanwhile, a Matsushima score was assigned from postoperative angiograms. Results: This study included 66 patients (67 hemispheres). During the follow-up period, a median of 18 (IQR, 13-21) months, no stroke or death occurred in any of the patients. The clinical outcomes were excellent in 27 patients (40.9%), good in 34 patients (51.6%), fair in 4 patients (6.0%), and poor in 1 patient (1.5%); the overall rate of favorable clinical outcomes (excellent and good) was 92.5%. The modified Rankin Scale (mRS) score was significantly improved at follow-up (P < 0.001). There were 41 hemispheres imaged by cerebral angiography after the operation, at a median postoperative interval of 9 (IQR, 8-12) months; among them, 34 (82.9%) hemispheres had Matsushima scores of grade A and grade B. The average postoperative diameters in the STA, DTA and MMA were increased significantly in 41 hemispheres at follow-up (P < 0.001). Sixteen (24.2%) patients suffered from perioperative complications, including focal hyperperfusion syndrome (HS) in 8 (12.2%) patients, cerebral infarction in 3 (4.5%) patients (including one case accompanied by wound infection), cerebral hemorrhage in 2 (3.0%) patients, seizures in 2 (3.0%) patients, and subdural effusion in 1 (1.5%) patient. Conclusions: The procedure of STA-MCA anastomosis combined with MBH surgery and dural inversion synangiosis may be a safe and effective treatment for adult patients with moyamoya disease.

The Guidewire-assisted Drainage Catheter Placement in Chronic Subdural Hematoma.

Background: Chronic subdural hematoma (cSDH) is a common neurosurgical pathology associated with older age. The burr hole drainage is a predominant technique with a lower incidence of recurrence and morbidity. The blind placement of the subdural drain could result in intracerebral hemorrhage. This paper describes a simple and reliable technique for drainage catheter placement in cSDH to reduce intracerebral hemorrhage. Methods: Forty-nine consecutive patients with cSDH were treated with The Guidewire-assisted Drainage Catheter Placement Technique between July 2019 and June 2021. Epidemiological, clinical and radiographical data were collected and reviewed. The operative technique consists of an angular guidewire tip and catheter. Under the navigation of the guidewire, the catheter is inserted into the subdural space and the length of catheter remaining in the subdural space was 4-5 cm. The catheter was tunneled subcutaneously and fixed at the point where it emerged from the scalp. Results: Forty-nine consecutive patients underwent 55 The Guidewire-assisted Drainage Catheter Placement. The gender distribution was 37 men and 12 women. The mean age was 69.3 years. The patients presented with headache (31 patients), weakness of limbs (28 patients), speech disturbances (7 patients), and Altered behavior (6 patients). Neither intracerebral hemorrhages nor post-operative seizure occurred. Forty-seven patients were improved after the operation. The recurrence occurred in one patient. Conclusions: The Guidewire-assisted Drainage Catheter Placement Technique is a reliable method for the insertion of a subdural catheter to evacuate of the Chronic Subdural Hematoma, and is associated with an extremely low risk to cortical structures and cerebral veins.