A mouse model replicating hippocampal sparing cranial irradiation in humans

A tool for identifying new strategies to limit neurocognitive decline

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9 Citations (Scopus)

Abstract

Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG<inf>0933</inf> study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C<inf>57</inf>BL/6J mice to a single dose of 10Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG<inf>0933</inf> clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation.

Original languageEnglish (US)
Article number14384
JournalScientific Reports
Volume5
DOIs
StatePublished - Sep 24 2015

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Cranial Irradiation
Brain
Radiation Injuries
Inbred C57BL Mouse
Hippocampus
Neoplasms
Cell Death
Animal Models
Clinical Trials
Control Groups
Cognitive Dysfunction

ASJC Scopus subject areas

  • General

Cite this

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title = "A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline",
abstract = "Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation.",
author = "Tome, {Wolfgang A.} and Solen Gokhan and Brodin, {Nils P.} and Gulinello, {Maria E.} and John Heard and Mehler, {Mark F.} and Chandan Guha",
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AU - Tome, Wolfgang A.

AU - Gokhan, Solen

AU - Brodin, Nils P.

AU - Gulinello, Maria E.

AU - Heard, John

AU - Mehler, Mark F.

AU - Guha, Chandan

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N2 - Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation.

AB - Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation.

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