Effects of postmortem interval on myelin integrity in rhesus macaque brain tissue

Abstract When conducting microscopy of human brain sections, the postmortem interval (PMI) introduces myelin‐related artifacts that can confound neuropathological interpretation, yet the extent and detectability of these changes remain poorly characterized. This study examined the impact of controlled PMI on myelin integrity in rhesus macaque brain tissue using advanced optical imaging approaches. Brains from five aged rhesus macaques (20.5–28.5 years) were maintained at 4°C and analyzed at 0, 24, and 72 h postmortem. Myelin integrity in white and gray matter was assessed using quantitative birefringence microscopy to measure relative retardance and polarization‐sensitive optical coherence tomography to quantify scattering coefficients, retardance, and volumetric features. Increasing PMI was associated with progressive myelin degradation, reflected by significant reductions in relative optical retardance in white matter ( p < 0.01) and gray matter ( p < 0.001), alongside increased scattering coefficients in both regions ( p < 0.001). Morphological analyses revealed a marked increase in myelin defects per mm 2 with longer PMI ( p < 0.001), characterized by swellings, vesicles, and structural discontinuities. These findings demonstrate that PMI causes significant detectable myelin changes, which can be quantified using optical imaging techniques, providing critical implications for interpreting postmortem neuropathological studies (especially with human brain tissues) and establishing a need for standardized PMI considerations in research protocols to ensure accurate pathological assessment in neurological disease investigations.