Animal models measurement of injury

Fertility assessment in test animals has limited sensitivity as a measure of reproductive injury, because, unlike humans, males of most test species produce sperm in excess of the minimum requirements for fertility. In addition, test animals can undergo multiple matings (Amann, 1981 Working, 1988 Chapin Heindel, 1993). In some strains of rats and mice, production of sperm can be reduced by 90% or more without compromising fertility (Aafjes et al., 1980 Meistrich, 1982 Working, 1988) in human males, less severe reduction in sperm production can cause reduced fertility. Thus, measurement of change in sperm count or fertility in laboratory rodents may be insufficient to assess reproductive health risk in humans. Other animal models may be more suitable for assessing fertility (Chapin et al., 1998). However, it should not be assumed that a reduction in sperm count (i.e., <90%) will have no effect on fertility in rodents (Wine et al., 1997). 

Our insight into the development, evolution and the mechanisms of damage in cerebral ischemia is mainly based on animal studies. A large variety of experimental models have been developed that imitate conditions of stroke and cardiac arrest (Hossmann 1991). In the past, experiments had to be terminated at certain timepoints to obtain invasive measurements of lesion size, blood flow, metabolism or other markers of injury. Therefore, longitudinal observations required large animal numbers and the inter-individual differences complicated the analysis of results. The advent of MR techniques of imaging... 

There is a significant increase in cellular proliferation by surviving proximal tubular cells after renal injury in both animal models [68] and human cases of acute tubular necrosis [43] as measured by PCNA... 

Uchida 2003). However, the presence of those adducts as a cause of the disease or only as a consequence of the accompanying oxidative stress is still a matter of debate. In an animal model of hepatic oxidative injury, the formation of HNE adducts with specific proteins appears very early, several hours before clinical and histopathologi-cal signs, suggesting a possible mechanistic role of HNE (Petersen and Doom 2004). Lipid oxidation protein adducts are often used as biomarkers of lipid peroxidation/ oxidative stress. They can be measured by immunological or mass spectrometry methods. For a review, see Spickett (2013). 

This condition is referred to as ischemia-reperfusion injury. Several studies in animal models of ischemia-reperfusion injury have shown that the principal cause of cellular death is necrosis (11-13). However, other smdies have shown that cellular death consisted of a necrotic core surrounded by a peri-necrotic area that displayed properties consistent with apoptosis (11,14-18). Therefore, it is likely that cellular death resulting from ischemia-reperfusion injury can consist of a mixture of apoptosis and necrosis, depending on the extent and duration of the ischemia prior to reperfusion. Other disease conditions where evidence demonstrating both apoptosis and necrosis occur includes diabetic cardiomyopathy, sepsis, stroke, and the neurodegenerative disorders Alzheimer s disease and Parkinson s disease. The development of a noninvasive imaging technique capable of measuring apoptosis and necrosis independently could provide valuable information on the balance between apoptosis and necrosis, and if there is a temporal shift in the balance of these mechanisms of cellular death, in a wide variety of pathological conditions. 

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