Improved functional outcome after chronic stroke with delayed anti-Nogo-A therapy: A clinically relevant intention-to-treat analysis
| Autor: | Shih-Yen Tsai, Katherine M Podraza, Yasmin Mehta, Timothy E. O'Brien, Vicki A. Husak, Gwendolyn L. Kartje, Elise Lippmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Nogo Proteins Skilled reaching Drug Evaluation Preclinical Antibodies 03 medical and health sciences recovery 0302 clinical medicine Physical medicine and rehabilitation medicine Animals Rats Long-Evans 030212 general & internal medicine Stroke Chronic stroke sensorimotor Intention-to-treat analysis business.industry Motor Cortex Immunotherapy Original Articles Dendrites Recovery of Function medicine.disease Anti-Nogo-A Preclinical data stroke Treatment efficacy Intention to Treat Analysis Rats chronic medicine.anatomical_structure Treatment Outcome Neurology Neurology (clinical) Forelimb Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Many preclinical treatment strategies for stroke have failed when tested in human trials. Although the reasons for these translation failures are multifactorial, one potential concern is the statistical analysis of the preclinical data. One way to rigorously evaluate new therapies is to use an intention-to-treat analysis in preclinical studies. Therefore, in this study, we set out to evaluate the treatment efficacy of a potential clinically relevant therapeutic agent for stroke, i.e., anti-Nogo-A immunotherapy, using an intention-to-treat analysis. Adult rats were trained on the skilled forelimb reaching task and subsequently underwent an ischemic stroke. Nine weeks later, the rats either received intracerebroventricular anti-Nogo-A antibody, control antibody, or no treatment. Skilled reaching performance was assessed by a non-linear model using both an intention-to-treat and per-protocol analysis. Following testing, dendritic complexity was evaluated in the contralesional and perilesional sensorimotor cortex. Both intention-to-treat and per-protocol analysis showed that anti-Nogo-A immunotherapy resulted in statistically significant improved recovery on the skilled forelimb reaching task, although treatment effect was less (though statistically significant) in the intention-to-treat group. Improved functional performance was not shown to be associated with dendritic changes. In conclusion, this study provides evidence for the importance of using intention-to-treat paradigms in testing preclinical therapeutic strategies. |
| Databáze: | OpenAIRE |
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