Basic NeuroscienceA new percutaneous model of Subarachnoid Haemorrhage in rats
Highlights
► We described a new rat model of SAH by percutaneous injection of autologous, non-heparinised blood into the intracisternal space. ► The model is reproducible, easy-to-perform and quick. ► The model presents low mortality rates and subsequent ischemic–haemorrhagic lesions.
Introduction
Patients with Spontaneous Subarachnoid Haemorrhage (SAH) have a high mortality rate within thirty days. This elevated level shows a slight tendency to descend, which is possibly related to the new diagnostic techniques and treatment (Sandvei et al., 2011). Although some clinical factors exist which improve prognosis by means of suitable intervention, a high percentage of the variables are non-modifiable (Andaluz and Zuccarello, 2008, Goldacre et al., 2008, Muñoz-Sánchez et al., 2009). Vasospasm secondary to SAH is the leading cause of sequelae following a ruptured aneurysm in the cerebral arteries (Dorsch, 2002). After day four, 30% of patients go on to develop symptomatic vasospasm (SV) (Vergouwen, 2011). At present our understanding of the pathophysiological events that occur after SAH is insufficient and this leads to two crucial facts: firstly, we do not have reliable tools to unmistakeably select the patients who are at risk for SV, and secondly, with the exception of nimodipine, there is no existing therapy to avoid or solve this complication. This leads to variability in the clinical management of patients worldwide (Stevens et al., 2009). For these reasons we must promote new lines of research that facilitate pathophysiological understanding of the phenomena associated with vasospasm after SAH, and test treatments that may induce changes in the mortality rates and in the number of disabling sequelae (Laskowitz and Kolls, 2010).
Despite the large number of species (rats, rabbits, dogs, etc.) used to conduct studies about vasospasms after SAH, rat models of SAH are quite widespread. This is due to the ease in handling, housing and cost (Megyesi et al., 2000). Since the studies by Barry et al. in 1979, multiple invasive models have been generated with large differences between them, without achieving the optimal model (Barry et al., 1979). We have aimed to produce a rat model of SAH that meets all the characteristics of an ideal experimental model: simple to perform, minimally invasive, efficient and that accurately reproduces the natural development of the disease.
Section snippets
Methods
The procedures were performed in the experimental operating room of the Seville Biomedicine Institute (Instituto de Biomedicina de Seville [IBiS]), Virgen del Rocío University Hospital, Seville, Spain. This research project was overseen and approved by our hospital's Animal Experimentation Committee. It met all ethical standards for research and legal requirements as established by the corresponding legislation (Directive 2010/63/EU).
Wistar rats (300–350 g) were used as the model. The procedure
Results
A total of 30 animals were operated on following the schema of the percutaneous intracisternal injection model.
Preliminary, we performed the procedure on four rats. We used the same system in terms of positioning the animal and location of the cisterna magna, except that instead of injecting fresh blood or physiological saline, we injected a volume of 100 μl methylene blue. The subsequent extraction of the brain showed that the dye had followed a proper distribution throughout the subarachnoid
Discussion
We present a new rat model of SAH which is simple to perform, minimally invasive, quick and with low mortality.
In literature there currently exist many rat models of SAH. These may be separated into three groups: the external vessel puncture under direct vision (Barry et al., 1979, Kader et al., 1990), the endovascular filament puncture (Veelken et al., 1995), and intracisternal injection through surgical procedures (Delgado et al., 1985, Solomon et al., 1985, Bederson et al., 1995).
The first
Conclusion
This paper details a new rat model of SAH by percutaneous injection of autologous, non-heparinised blood into the intracisternal space. This is a model which is reproducible, easy-to-perform, quick and it presents low mortality rates. This makes it very interesting for future studies on the delayed vasospasm complications of SAH.
Conflict of interest
The authors have no conflict of interests.
Acknowledgement
This study has been funded by Health Research Fund 2010 (Fondos de Investigación Sanitaria, FIS 2010) from the Instituto de Salud Carlos III, Spain.
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