Linkage of cell cycle kinetics between embryonic and adult stroke models: an analytical approach

Abstract

In the adult brain, neurogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle. The proliferating population and the cell cycle kinetics in the ventricular zone regulate cortical neurogenesis during the development. Using the embryonic model, we investigated kinetics of SVZ cells in adult rats after stroke, incorporating migration of SVZ cells to the ischemic boundary. Concurrent linear regressions were considered through iteration to improve precision of parameter estimation. We found no model-fit difference in stroke with and without the migration (p=0.31), suggesting no migration effect on assessment of the cell kinetics. Stroke increased SVZ cell proliferation (20% in non-stroke and 31% in stroke p<0.01). Cell cycle durations in stroke were reduced for the total cycle length (19h for non-stroke and 15.3h for stroke, p<0.05), in G1 phase (12.6 h for non-stroke and 9.6 h for stroke, p<0.01), but were the same in S, M2, and in G2 phases compared to non-stroke, indicating that stroke reduces the total cell cycle length, specially in G1 phase. We conclude that cell cycle kinetic models for cortical development can be adapted to the kinetics of adult SVZ cells after stroke. The analytical approach may be useful for studying neural progenitor cell proliferation under different treatments.