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.
Fukuda
Aya
A
Arvid Carlsson Institute for Neuroscience, Department of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, SE-405 30 Göteborg, Sweden.
Fukuda
Hirotsugu
H
Swanpalmer
Janos
J
Hertzman
Sven
S
Lannering
Birgitta
B
Marky
Ildiko
I
Björk-Eriksson
Thomas
T
Blomgren
Klas
K
D000367:Age Factors; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001921:Brain / Q000254:growth & development* / Q000473:pathology / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D018891:Dentate Gyrus / Q000254:growth & development / Q000473:pathology / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000528:radiation effects; D020547:Lateral Ventricles / Q000254:growth & development / Q000473:pathology / Q000528:radiation effects; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D010315:Particle Accelerators; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D011836:Radiation Tolerance / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000473:pathology / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000943:Antigens, Differentiation; D016159:Tumor Suppressor Protein p53; C002744:3-nitrotyrosine; D014443:Tyrosine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases