Belastungseinschätzung von Ratten im endovaskulären Gefäßperforationsmodell der Subarachnoidalblutung

The severity assessment required by the EU Directive 2010/63/EU has so far been based primarily on subjective, often not scientifically validated criteria. In the study conducted here, a multimodal approach using objectively measurable parameters was chosen to assess the severity of rats in the endovascular perforation model of subarachnoid haemorrhage (SAH). Male Wistar rats with SAH were studied in comparison to sham operated animals or animals without surgery (only anaesthesia and analgesia, anaesthesia group). The sham and SAH animals showed an increase in the clinical score on the first postoperative days. A significant body weight loss was observed, too, especially in animals with severe SAH. The analyses of the behavioural tests (open field, burrowing, balance beam, beam walk and neuroscore) showed changes in sham as well as SAH animals in the sense of an impairment showing primarily an influence of the surgery. Only the balance beam and the neuroscore allowed some differentiation between sham and SAH. The lack of differences in the anaesthesia group indicates that the performance of several tests in succession and repetitively over several days has little influence on the animals. The principal component analysis allowed a separation from the baseline for sham and SAH on the first postoperative days, which confirms the findings from the individual tests regarding a significant influence of the surgical procedure on the animals compared to the SAH itself. The value of the selected tests for an objective assessment of the severity could thus be confirmed. The analysis of the corticosterone levels in serum did not show any evidence of SAH induced activation of the pituitary-hypothalamic-adrenal axis. The measurement of faecal corticosterone metabolites suggested an increase in stress levels in some animals due to SAH. Serum IL6 levels in the SAH animals increased on the first days postoperatively, indicating an SAH induced pro-inflammatory event. In the context of this study, we have thus succeeded in a multimodal approach to demonstrate, on the basis of objectively measurable parameters, a burden of the animals on the first postoperative days which was primarily caused by the surgical intervention. Further investigations using other SAH models as well as the comparison with other neuronal and non-neuronal disease models are necessary in order to be able to make a final, objective and validated assignment of this model to one of the severity categories specified in the EU Directive 2010/63/EU