Abstract
Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research. We here systematically evaluated other measures as surrogates for a more reliable humane endpoint determination. Adult male BDIX rats (n = 119) with intracranial glioma formation after BT4Ca cell-injection were used. Clinical score and body weight were assessed daily. One subgroup (n = 14) was assessed daily for species-specific (nesting, burrowing), motor (distance, coordination) and social behaviour. Another subgroup (n = 8) was implanted with a telemetric device for monitoring heart rate (variability), temperature and activity. Body weight and clinical score of all other rats were used for training (n = 34) and validation (n = 63) of an elaborate body weight course analysis algorithm for endpoint detection. BT4Ca cell-injection reliably induced fast-growing tumours. No behavioural or physiological parameter detected deteriorations of the clinical state earlier or more reliable than clinical scoring by experienced observers. However, the body weight course analysis algorithm predicted endpoints in 97% of animals without confounding observer-dependent factors. Clinical scoring together with the novel algorithm enables highly reliable and observer-independent endpoint determination in a rodent intracranial tumour model.
Highlights
Humane endpoint determination is fundamental in animal experimentation
In experimental rodent studies dealing with intracranial tumour formation, humane endpoints are often described in an imprecise way or even not mentioned at all, survival rates are commonly used for Kaplan-Meier survival analysis
Rats recovered after intracranial tumour cell injection within one day without relevant deterioration of clinical scores and weight-loss
Summary
Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research. Clinical scoring together with the novel algorithm enables highly reliable and observer-independent endpoint determination in a rodent intracranial tumour model. Models of fast-growing intracranial tumours, such as gliomas, are especially demanding in the definition of humane endpoints The progression of this disease is often characterized by a long asymptomatic phase despite the considerable dimension of the tumour, followed by a sudden and severe deterioration of the clinical condition[7,10]. A more elaborate analysis of the body weight course can lead to strategies for a more objective definition of endpoint criteria This has already been proposed but has not yet been applied with sufficient accuracy[3]
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