In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice. Video LinkThe video component of this article can be found at

Genetically engineered mice are a valuable tool to investigate the molecular and cellular mechanisms leading to brain damage following subarachnoid hemorrhage (SAH). Therefore, several murine SAH models were developed during the last 15 years. Among those models, the perforation of the Circle of Willis by an endovascular filament or "filament model" turned out to become the most popular one, since it is believed to reproduce some of the most prominent pathophysiological features observed after human SAH. Despite the importance of the endovascular filament model for SAH research, relatively few studies were published using this technique during the past years and a number of laboratories reported problems establishing the technique. This triggered discussions about the standardization, reproducibility, and the reliability of the model. In order to improve this situation, the current paper aims to provide a comprehensive hands-on protocol of the murine endovascular filament model. The protocol proved to result in induction of SAH in mice with high intrapersonal and interpersonal reproducibility and is based on our experience with this technique for more than 10 years. By sharing our experience with this valuable model, we aim to initiate a constantly ongoing discussion process on the improvement of standards and techniques in the field of experimental SAH research.

Subarachnoid hemorrhage (SAH) is a stroke subtype associated with high mortality and morbidity as a result of early and delayed ischemic processes. Nearly one quarter of all patients with SAH die shortly after hemorrhage because of elevated intracranial pressure (ICP) and the resulting global cerebral ischemia.1,2 Hospitalized patients further experience severe complications, including rebleeding, early brain injury, and delayed cerebral ischemia, which together contribute to a devastatingly high 1-month mortality rate of 50%. 1,2 Early brain injury is the predominant cause of death after SAH and is characterized by elevated ICP, decreased cerebral blood flow (CBF), and global cerebral ischemia resulting in secondary injuries, including disruption of the blood-brain barrier, inflammation, and oxidative stress, which all cause neuronal cell death. [3][4][5] In both animal and clinical studies, the severity of bleeding and the extent of decreased CBF correlated with neurological outcome [6][7][8] ; however, how and to what extent the initial global ischemia or subsequent elevated ICP contribute to early brain injury remains poorly understood. [3][4][5] A feasible way to reduce elevated ICP is decompressive craniectomy (DC), a technique that dates back more than a century. 9 In recent years, both animal and clinical studies reported beneficial effects of DC for treating conditions, such as traumatic brain injury 10,11 and malignant middle cerebral artery (MCA) infarction. 12,13 With respect to SAH, however, relatively few studies have been published regarding the application of DC and its effect on outcome; moreover, the results published to date are contradictory and controversial. [14][15][16][17][18] To address these questions, we performed DC to evaluate the role of SAH-induced elevated ICP and subsequent global ischemia and to investigate whether DC may serve as a therapeutic option for SAH using a standardized animal model. MethodsIn total, 41 male C57BL/6 mice (22-25 g; Charles River Laboratories, Sulzfeld, Germany) were used. All experiments were approved by the Government of Upper Bavaria (protocol number 55.2.1.54-2532-90-13) and were performed in accordance with standard ethical guidelines. Experimental DesignInitially, 40 animals were assigned randomly to the following 4 experimental groups: sham surgery, SAH, DC after SAH, and DC before SAH (Figure 1). All assessments were performed by an Background and Purpose-Elevated intracranial pressure (ICP) is a key feature of subarachnoid hemorrhage (SAH). Here, we examined the role of elevated ICP in the pathophysiology of SAH, and we investigated whether decreasing ICP by performing decompressive craniectomy (DC) can improve outcome. Methods-SAH was induced in male C57BL/6 mice via endovascular Circle of Willis perforation in the following 4 groups:sham surgery, SAH, DC after SAH, and DC before SAH. DC was performed either 15 minutes before or after SAH induction. ICP, cerebral blood flow, heart rate, oxygen saturation, and end-tidal PCO 2 were monitored for ...

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