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Incomplete Assessment of Experimental Cytoprotectants in Rodent Ischemia Studies

Published online by Cambridge University Press:  02 December 2014

Suzanne B. DeBow ,
Darren L. Clark ,
Crystal L. MacLellan  and
Frederick Colbourne
Suzanne B. DeBow
Affiliation:
Department of Psychology and Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Darren L. Clark
Affiliation:
Department of Psychology and Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Crystal L. MacLellan
Affiliation:
Department of Psychology and Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
Frederick Colbourne
Affiliation:
Department of Psychology and Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada
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Abstract

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Background:

Inadequate preclinical testing (e.g., rodent studies) has been partly blamed for the failure of many cytoprotectants to effectively treat stroke in humans. For example, some drugs went to clinical trial without rigorous functional and histological assessment over long survival times. In this study, we characterized recent experimental practices in rodent cytoprotection experiments to determine whether the limitations of early studies have been rectified.

Methods:

We identified 138 rodent cytoprotection studies published in several leading journals (Journal of Neuroscience, Stroke, Journal of Cerebral Blood Flow and Metabolism and Experimental Neurology) for 2000 - 2002 and compared these to those published in 1990. From each study we determined the ischemia model, age and sex of the animal, the histological and functional endpoints used, and the methodology used to assess intra- and postischemic temperature.

Results:

Ninety-eight percent of recent studies used young adult rodents and most used males. Most studies (60%) did not assess functional outcome and survival times were often ≤ 48 hr (66%) for focal ischemia and ≤ 7 days (80%) for global ischemia. Over 60% of the experiments relied solely upon rectal temperature during ischemia and only 32.6% of ischemia studies measured temperature after surgery. The 1990 data were similar.

Conclusion:

Many investigators ignore the need to assess long-term functional and histological outcome and do not accurately represent clinical conditions of ischemia (e.g., use of aged animals). In addition, intra- and postischemic temperature measurement and control is frequently neglected or inadequately performed. Further clinical failures are likely.

Résumé:

RÉSUMÉ: Introduction:

Une évaluation préclinique inadéquate (i.e. études chez les rongeurs) semble en partie responsable de l'inefficacité de plusieurs cytoprotecteurs pour traiter l'accident vasculaire cérébral chez l'humain. À titre d'exemple, certains médicaments ont atteint la phase des essais thérapeutiques sans évaluation fonctionnelle et histologique rigoureuse à long terme. Dans cette étude, nous décrivons les pratiques expérimentales actuelles au cours d'évaluations de cytoprotection chez les rongeurs pour déterminer si les lacunes des études antérieures ont été corrigées.

Méthodes:

Nous avons identifié 138 études de cytoprotection chez des rongeurs publiées dans plusieurs journaux prestigieux (Journal of Neuroscience, Stroke, Journal of Cerebral Blood Flow and Metabolism et Experimental Neurology) de 2000 à 2002 et nous les avons comparées à celles publiées en 1990. Pour chaque étude, nous avons examiné le modèle d'ischémie, l'âge et le sexe des animaux, les critères d'évaluation histologiques et fonctionnels et la méthodologie utilisée pour évaluer la température infra et postischémie.

Résultats:

Quatre-vingt-dix pour cent des études portaient sur de jeunes rongeurs adultes et la plupart étaient des mâles. La plupart des études (60%) n'évaluaient pas l'issue fonctionnelle et le temps de survie était souvent de £ 48 heures (66%) pour l'ischémie focale et de £ 7 jours (80%) pour l'ischémie globale. Plus de 60% des études étaient basées uniquement sur la température rectale pendant l'ischémie et seulement 32.6% des études mesuraient la température après la chirurgie. Les données de 1990 étaient semblables.

Conclusions:

Plusieurs chercheurs ignorent l'importance d'évaluer les résultats fonctionnels et histologiques à long terme et ne reproduisent pas avec exactitude les conditions cliniques de l'ischémie (i.e., utilisation d'animaux âgés). De plus, la mesure et le contrôle de la température infra et postischémie sont souvent négligés ou faits de façon inadéquate. D'autres échecs cliniques sont à prévoir.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 30 , Issue 4 , November 2003 , pp. 368 - 374
Copyright
Copyright © The Canadian Journal of Neurological 2003

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