| Experimental Models of Human Diasease | |||||
| When developig an animal model to test its efficacy of a compound, what are your concerns? | |||||
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Does the model truly resemble the human disease being targeted? Many diseases have unique features and the animal model must have such features, particularly if the compound to be tested is designed to block, modify or enhance them. An early histopathologic evaluation during the selection of an animal model will ensure that the model is correctly reproduced, and that it accurately mimics the human disease being targeted. |
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| Peracute cardiac infarct in a mouse. Note the change in staining affinity (arrow). The area of necrosis is almost imperceptible at low power. | |||||
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Are the lesions and their severity consistently reproduced and measurable? You well know that success of an efficacy study depends on the reliability of the end-point used to measure the compound effect. If the severity of lesions and their incidence are underexpressed, the results of the study will be brought into question. A failure to measure changes with accuracy and sensitivity may cause the need to repeat studies. On the other hand, if the severity of lesions is grave, many animals will die irrespective of treatment, bringing doubt to the statistical certainty of the results. |
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| Higher magnification of heart muscle above. Note the loss of stration of myocytes, hemorrhage, and vacuolation of myocytes in the area of necrosis. Although the lesion is subtle, it is significant enough to explain the acute death of the affected mouse. Without a histologic examination, the death would have been unexplained |
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Histopathology Gives you Accuracy and Sensitivity! A histopathologic examination of the target organs will provide you with that sensitivity. Further, immunohistochemistry and in situ hybridization techniques may be used to trace markers of interest at the site of injury or elsewhere. The implementation of image analysis techniques can further improve on the sensitivity of your measurements, particularly when looking at subtle changes such as apoptosis or cell proliferation in neoplasms or other conditions. |
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