Animal Models of Demyelinating Disease
In these platforms, the demyelination process characteristic of multiple sclerosis in humans is recapitulated in mice (cuprizone-induced) or rats (LPC-induced).
Our flexible study paradigms allow for multiple behavioral, imaging and biomarker assessments, as well as client-specified dosing programs, providing a comprehensive evaluation of the efficacy of your MS therapy candidates in these models.
Following 6 weeks of cuprizone administration, mice exhibit characteristic behaviors of demylination, including impaired gross and fine motor performance as well as increased anxiety and abnormal contextual fear conditioning response. Behavioral observations are supported by quantifying the extent of the pathology using DTI-MRI and SPECT/CT.
Once cuprizone administration is halted, remyelination is observed. Remyelination has become a target for MS therapeutic development because of its potential to decrease the extent of axonal degeneration.
Example of the cuprizone-induced demyelination study paradigm (6 weeks with cuprizone in diet, followed by three weeks without). Treatment regimen is study-dependent.
Distance traveled and vertical rearing were both significantly reduced compared to control group after 6 weeks on a cuprizone diet, indicative of impaired motor performance. Three weeks after cuprizone was stopped, the groups do not show a significant difference in either test.
After 3 weeks on cuprizone diet, there was no significant difference in performance on the rotarod test of motor performance. However, a significant deficit performance on the same test compared to the control was observed after 6 weeks on the cuprizone diet.
After 6 weeks on cuprizone, mice exhibited a significantly lower percent of time in open arms. Time in center and visits in open arms were unchanged compared to control.
Apparent pathology in white matter of mice on cuprizone diet (demyelination) already at 3 weeks as evidenced by DTI-MRI.
123I-TSPO binding is significantly induced in the cerebrum and cerebellum of naive and cuprizone-treated mice at 6 weeks post-cuprizone treatment, suggesting increased inflammation in the brain. Axial view indicates 123I-TSPO binding with blue to red signal (left), and quantitation (right) reveals statistically significant changes (p<0.01).
Focal LPC-induced Demyelination
In this platform, demyelination is induced in defined lesion areas in rats through direct infusion of lysolecithin (LPC). Subsequent destruction of white matter is evaluated and visualized with MRI and lesions co-localized with immunohistochemical analyses for myelin basic protein (MBP).