Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given three weeks before aneurysm induction and either continued until the end of the experiment or stopped one day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started three weeks before aneurysm induction and continued until the end of the experiment (83% vs. 6%, P < 0.001). Even when antibiotics were stopped one day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% vs. 28%, P < 0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.

abbreviatioNs GCS = Glasgow Coma Scale; mRS = modified Rankin Scale; SDH = subdural hematoma. subMitted April 30, 2014. accepted October 17, 2014. iNclude wheN citiNg Published online April 24, 2015; DOI: 10.3171/2014.10.JNS14915. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Endoscopic hematoma evacuation for acute and subacute subdural hematoma in elderly patientsKimihiko Yokosuka, Md, phd, Masaaki uno, Md, phd, Kohei Matsumura, Md, hiroki takai, Md, hirotaka hagino, Md, Nobuhisa Matsushita, Md, phd, hiroyuki toi, Md, and shunji Matsubara, Md, phd Department of Neurosurgery, Kawasaki Medical School, Kurashiki, Okayama, Japan obJect Endoscopic surgery was performed for acute or subacute subdural hematoma (SDH), and its effectiveness and safety in elderly patients were evaluated. Methods Between September 2007 and November 2013, endoscopic surgery was performed in 11 elderly patients with acute SDH (8 patients) and subacute SDH (3 patients). The criteria for surgery were as follows: 1) the presence of clinical symptoms; 2) age older than 70 years; 3) no brain injury (intracerebral hematoma, brain contusion); 4) absence of an enlarging SDH; and 5) no high risk of bleeding. Hematoma evacuation was performed with a 4-mm rigid endoscope with a 0° lens and a malleable irrigation suction cannula. results Endoscopic surgery was performed under local anesthesia. The mean age of the patients was 82.6 years (range 73-91 years). There were 5 female and 6 male patients. The mean preoperative Glasgow Coma Scale score was 12, and 5 patients had been receiving antithrombotic drug therapy. The mean operation time was 85 minutes. Only 1 patient had rebleeding, and reoperation with the same technique was performed uneventfully in this individual. A total of 7 patients had a good recovery (modified Rankin Scale Score 0-2) at discharge. coNclusioNs Endoscopic hematoma evacuation of acute and subacute SDH is a safe and effective method of clot removal that minimizes operative complications. This technique may be a less invasive method for treating elderly patients with acute and subacute SDHs.

Potential roles for neutrophils in the pathophysiology of intracranial aneurysm have long been suggested by clinical observations. The presence of neutrophil enzymes in the aneurysm wall has been associated with significant increases in rupture risk. However, the mechanisms by which neutrophils may promote aneurysm rupture are not well understood. Neutrophil extracellular traps (NETs) were implicated in many diseases that involve inflammation and tissue remodeling, including atherosclerosis, vasculitis, and abdominal aortic aneurysm. Therefore, we hypothesized that NETs may promote the rupture of intracranial aneurysm, and that removal of NETs can reduce the rate of rupture. We employed both pharmacological and genetic approaches for the disruption of NETs and used a mouse model of intracranial aneurysm to investigate the roles of NETs in the development of intracranial aneurysm rupture. Here, we showed that NETs are detected in human intracranial aneurysms. Both global and granulocyte-specific knockout of peptidyl arginine deiminase 4 (an enzyme essential for NET formation) reduced the rate of aneurysm rupture. Pharmacological blockade of the NET formation by Cl-amidine also reduced the rate of aneurysm rupture. In addition, the resolution of already formed NETs by deoxyribonuclease was effective against aneurysm rupture. Inhibition of NETs formation with Cl-amidine decreased mRNA expression of proinflammatory cytokines (intercellular adhesion molecule 1 (ICAM-1), interleukin 1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α)) in cerebral arteries. These data suggest that NETs promote the rupture of intracranial aneurysm. Pharmacological removal of NETs, by inhibition of peptidyl arginine deiminase 4 or resolution of already-formed NETs, may represent a potential therapeutic strategy for preventing aneurysmal rupture.

Background and Purpose: Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically-active constituent of tobacco products. Nicotine’s interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods: Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single elastase injection into cerebrospinal fluid in mice. Results: Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Co-exposure to an α7*-nAChR antagonist abolished nicotine’s deleterious effect. Additionally, nicotine’s promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice, but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced up-regulation of these growth factors and cytokines. Conclusion: Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.

Background:Chronic encapsulated intracerebral hematoma (CEIH) is one type of intracerebral hematoma that sometimes grows progressively while forming a capsule and presenting with neurological deficits. Although many cases of CEIH have been reported, correct preoperative diagnosis is very difficult. Only around 20% of cases are diagnosed preoperatively.Case Description:We encountered three cases of CEIH in which causes were unidentified and difficult to diagnose. All three cases were treated surgically. In the first case, a 59-year-old male was diagnosed preoperatively with metastatic brain tumor. In the second case, a 62-year-old female was diagnosed preoperatively with glioblastoma. The third case involved a 58-year-old female diagnosed preoperatively with CEIH.Conclusion:We should keep in mind that CEIH is a differential diagnosis for intracerebral space-occupying lesions. This report describes these three cases and discusses imaging findings and characteristics of CEIH.