Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells

• In a newly established model of unilateral, irradiation (IR)-induced injury we compared the outcome after IR to the immature and juvenile brain, using rats at postnatal days 9 or 23, respectively. We demonstrate that (i) the immature brains contained more progenitors in the subventricular zone (SVZ) and subgranular zone (SGZ) compared with the juvenile brains; (ii) cellular injury, as judged by activation of caspase 3 and p53, as well as nitrotyrosine formation, was more pronounced in the SVZ and SGZ in the immature brains 6 h after IR; (iii) the number of progenitor and immature cells in the SVZ and SGZ decreased 6 h and 7 days post-IR, corresponding to acute and subacute effects in humans, respectively, these effects were more pronounced in immature brains; (iv) myelination was impaired after IR at both ages, and much more pronounced after IR to immature brains; (v) the IR-induced changes remained significant for at least 10 weeks, corresponding to late effects in humans, and were most pronounced after IR to immature brains. It appears that IR induces both an acute loss of progenitors through apoptosis and a perturbed microenvironment incompatible with normal proliferation and differentiation, and that this is more pronounced in the immature brain.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Age Factors

Animals

Antigens

Differentiation/biosynthesis

Brain/*growth & development/pathology/*radiation effects

Caspases/metabolism

Cell Count

Dentate Gyrus/growth & development/pathology/radiation effects

Disease Models

Animal

Female

Lateral Ventricles/growth & development/pathology/radiation effects

Laterality/radiation effects

Male

Myelin Sheath/metabolism/pathology

Particle Accelerators

Radiation Injuries

Experimental/*metabolism/pathology

Radiation Tolerance/*physiology

Rats

Rats

Wistar

Research Support

Non-U.S. Gov't

Stem Cells/pathology/*radiation effects

Tumor Suppressor Protein p53/metabolism

Tyrosine/*analogs & derivatives/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)