A Murine Model of Subarachnoid Hemorrhage

Schüller, Kathrin; Bühler, Dominik; Plesnila, Nikolaus

doi:10.3791/50845

Cited by 23 publications

(33 citation statements)

References 15 publications

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“…[19][20][21] In brief, the neck was opened by a midline incision, and the left common carotid artery was exposed. A 5-0 monofilament was introduced into the internal carotid artery via the external carotid artery and advanced toward the Circle of Willis.…”

Section: Endovascular Perforation Model For Sah Inductionmentioning

confidence: 99%

“…Regions of interest (0.3×0.2 mm 2 ) were by guest on May 12, 2018 http://stroke.ahajournals.org/ Downloaded from selected in the CA1, CA2, and CA3 regions of the hippocampus, and viable pyramidal neurons were counted as previously described. [19][20][21] Neurons were counted in 3 sections (at 50-μm intervals), and the results are expressed as the mean of these 3 sections.…”

Section: Quantification Of Neuronal Damagementioning

confidence: 99%

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Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

Bühler

Azghandi

Schüller

et al. 2015

Stroke

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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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Section: Endovascular Perforation Model For Sah Inductionmentioning

confidence: 99%

Section: Quantification Of Neuronal Damagementioning

confidence: 99%

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

Bühler

Azghandi

Schüller

et al. 2015

Stroke

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“…The main reason for this popularity is that it mimics the burst of a cerebral aneurysm and most of its sequels reasonably well and is therefore believed to have a superior clinical relevance as compared to all other available models [ 17 ]. Good examples for the translational potential of the filament model are reports demonstrating delayed cerebral vasospasm [ 8 , 12 – 14 ], neurological dysfunction [ 9 , 11 – 13 , 15 ], brain edema formation [ 9 , 11 , 18 – 20 ], and a clinically relevant mortality of approximately 30 % [ 9 , 11 , 15 , 19 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Protocol for the Induction of Subarachnoid Hemorrhage in Mice by Perforation of the Circle of Willis with an Endovascular Filament

Bühler¹,

Schüller²,

Plesnila

2014

Transl. Stroke Res.

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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.

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“…Following failure of the righting reflex, mice were placed on a warmed platform in the supine position and the femoral artery was catheterized along with the tail vein for blood gas analysis and drug administration, respectively. SAH was induced by endovascular perforation using a 5‐0 monofilament suture at the terminal of the left internal carotid artery as described . In sham‐operated mice, the suture was introduced into the internal carotid artery, but without vessel perforation.…”

Section: Methodsmentioning

confidence: 99%

“…SAH was induced by endovascular perforation using a 5-0 monofilament suture at the terminal of the left internal carotid artery as described. [15][16][17][18] In sham-operated mice, the suture was introduced into the internal carotid artery, but without vessel perforation. After SAH induction, mice were recovered from anaesthesia and rested in a warmed cage.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage

Mutoh

Nakamura

et al. 2017

Clin Exp Pharma Physio

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Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator.

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A Murine Model of Subarachnoid Hemorrhage

Cited by 23 publications

References 15 publications

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

Effect of Decompressive Craniectomy on Outcome Following Subarachnoid Hemorrhage in Mice

Protocol for the Induction of Subarachnoid Hemorrhage in Mice by Perforation of the Circle of Willis with an Endovascular Filament

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage

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