The Need for Diversity in Animal Models
The clinical population is diverse, including both sexes, older individuals, and those with comorbid conditions such as diabetes, hypertension, and cardiovascular disease. Yet, standard preclinical models fail to reflect this. For example, aged male and female animals exhibit distinct differences in functional recovery following a stroke compared to younger males, underscoring the influence of age and sex on therapeutic outcomes. By incorporating a broader range of subjects, such as older animals and those with comorbid conditions, preclinical models can better capture the variability observed in clinical populations. This approach not only deepens our understanding of treatment efficacy across different demographics, but also enhances the translatability of findings, ultimately supporting the development of therapies that are more effective in real-world settings.
Limitations of Homogeneous Models
A staggering 75% to 85% of rodent studies are conducted in young, healthy male animals of the same strain and weight. These models lack the diversity seen in clinical stroke populations, where variables such as age, sex, race, and comorbidities greatly influence outcomes. For example, while clinical trials measure functional recovery, preclinical studies frequently focus on infarct size. This narrow scope fails to capture the broader physiological and functional complexities observed in patients.
In contrast to clinical trials, preclinical studies focus on infarct size, exclude comorbidities, and involve less randomization and blinding.
Comorbidities and Functional Outcomes
Studies reveal that comorbidities such as diabetes significantly impact treatment efficacy. In a Morris water maze assay, rats with diabetes performed worse in learning and memory tasks compared to healthy rats, even when treated with the test item.
Morris water maze assay in 4VO rats shows the test item's effectiveness in healthy rats but reduced effectiveness in diabetic rats.
Similarly, in the focal cerebral ischemic model (MCAo) of stroke, young and aged males and females exhibited differing responses in grip strength tests, highlighting the critical influence of age and comorbidities on stroke outcomes.
Grip test in MCAo rodents shows differences between young and ages males and also between aged males and aged females.
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