Progenitor cell injury after irradiation to the developing brain can be modulated by mild hypothermia or hyperthermia.
Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose of 8 Gy and animals were randomized to normothermia (rectal temperature 36 degrees C for 4 h), hypothermia (32 degrees C for 4 h) or hyperthermia (39 degrees C for 4 h). Cellular injury, e.g. chromatin condensation and nitrotyrosine formation, appeared to proceed faster when the body temperature was higher. Caspase-3 activation was more pronounced in the hyperthermia group and nuclear translocation of p53 was less pronounced in the hypothermia group 6 h after IR. In the SVZ the loss of nestin-positive progenitors was more pronounced (48%) and the size was smaller (45%) in the hyperthermia group 7 days post-IR. Myelination was not different after hypo- or hyperthermia. This is the first report to demonstrate that hypothermia may be beneficial and that hyperthermia may aggravate the adverse side-effects after radiation therapy to the developing brain.
Fukuda
Aya
A
The Arvid Carlsson Institute of Neuroscience at the Institute of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Fukuda
Hirotsugu
H
Jönsson
Marie
M
Swanpalmer
Janos
J
Hertzman
Sven
S
Lannering
Birgitta
B
Björk-Eriksson
Thomas
T
Màrky
Ildikó
I
Blomgren
Klas
K
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000254:growth & development / Q000503:physiopathology / Q000528:radiation effects*; D001925:Brain Damage, Chronic / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018891:Dentate Gyrus / Q000254:growth & development / Q000503:physiopathology / Q000528:radiation effects; D005260:Female; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007036:Hypothermia, Induced; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000502:physiology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D011839:Radiation, Ionizing; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000502:physiology / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016159:Tumor Suppressor Protein p53; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases