Abstract
Radiation effectively treats brain tumors and other pathologies but dose and treatment
plans are limited by normal tissue injury, a major cause of morbidity in survivors.
Clinically significant normal tissue injury can occur even with therapies that target
pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms
underlying normal tissue injury is facilitated by studying the effects of focal irradiation
and comparing irradiated and un-irradiated tissue in experimental animals. Young adult
rats were irradiated using the Leksell Gamma Knife® with a 10 Gy maximum dose directed at the left hippocampus and shaped to minimize irradiation
contralaterally. At least 95% of targeted hippocampus received ≥3 Gy, while all points in the contralateral hippocampus received <0.3 Gy. Neuronal and microglial markers of damage were assessed in the targeted and contralateral
hemispheres of Gamma Knife®-treated rats and compared to non-irradiated controls.
Acute cell death and sustained changes in neurogenesis and in microglia occurred in
the dentate gyrus of the targeted, but not the contralateral, hippocampus, providing
experimental evidence that focal irradiation at doses received by peri-target regions
during targeted radiation therapy produces robust normal tissue responses. Additional
studies using this approach will facilitate assessment of in vivo dose responses and
the cellular and molecular mechanisms of radiation-induced brain injury.
Keywords
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Article info
Publication history
Published online: April 11, 2011
Accepted:
March 10,
2011
Received in revised form:
March 10,
2011
Received:
January 7,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
