Transient inflammation in neurogenic regions after irradiation of the developing brain.
We characterized the inflammatory response after a single dose of 8 Gy to the brains of postnatal day 9 rats. Affymetrix gene chips revealed activation of multiple inflammatory mechanisms in the acute phase, 6 h after irradiation. In the subacute phase, 7 days after irradiation, genes related to neurogenesis and cell cycle were down-regulated, but glial fibrillary acidic protein (GFAP) was up-regulated. The concentrations of 14 different cytokines and chemokines were measured using a microsphere-based xMAP technology. CCL2, Gro/KC and IL-1alpha were the most strongly up-regulated 6 h after irradiation. CCL2 was expressed in astrocytes and microglia in the dentate gyrus and the subventricular zone (SVZ). Hypertrophy, but not hyperplasia, of astrocytes was demonstrated 7 days after irradiation. In summary, we found transient activation of multiple inflammatory mechanisms in the acute phase (6 h) after irradiation and activation of astrocytes in the subacute phase (7 days) after irradiation. It remains to be elucidated whether these transient changes are involved in the persistent effects of radiation observed on neurogenesis and cognition in rodents.
Kalm
Marie
M
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Fukuda
Aya
A
Fukuda
Hirotsugu
H
Ohrfelt
Annika
A
Lannering
Birgitta
B
Björk-Eriksson
Thomas
T
Blennow
Kaj
K
Márky
Ildikó
I
Blomgren
Klas
K
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001253:Astrocytes / Q000378:metabolism / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005911:Gliosis / Q000473:pathology; D007118:Immunoassay; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000378:metabolism / Q000528:radiation effects; D055495:Neurogenesis; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015415:Biomarkers; D018932:Chemokine CCL2