Irradiation After Surgically Induced Brain Injury in the Rat: Timing in Relation to Severity of Radiation Damage

Abstract

The aim of this study was to evaluate how timing of irradiation after brain surgery in rats relates to overall extent of brain radiation damage. Extent of injury was determined according to lipid peroxidation (malondialdehyde; MDA) levels in brain tissue. Thirty female rats were randomly assigned to five equal groups (Groups A-E). Four groups underwent trephination and scalpel hemisection of right frontal lobe. Rats in Groups B and D received 25 Gy cranial irradiation in a LINAC system at 10 and 20 days after surgery, respectively. Twenty-four hours later they were killed and their right frontal lobes were removed for lipid peroxidation determination. Groups A and C were not irradiated; these groups were killed and had their frontal lobes removed on day 11 and day 21 post-surgery, respectively. The remaining six animals (Group E, sham surgery) underwent trephination only, and were killed and had their frontal lobes removed 24 h later. There was a significant difference between the mean MDA levels in the control group and Group D, and between the levels in Group B and Group D (P < 0.05 for both). The difference between the mean for Group A and the mean for Group B was even more significant (P < 0.01). The most striking differences were between the control group and Group B, and between Group B and Group C (P < 0.001 for both). The data from this rat model suggest that, in humans, starting radiotherapy early (1-2 weeks) after debulking of a brain tumor may result in significantly higher levels of tissue damage than if the radiation is started 3 weeks or more postoperatively. Further experimental research is needed to project these findings in rats to human subjects.

The Evaluation of the Oxidant Injury as a Function of Time Following Brain Irradiation in a Rat Model

“…Peker et al compared the MDA levels in the brain in the rats that underwent irradiation in a single fraction of 25 Gy either at 10 days or at 20 days following brain surgery consisting of right frontal lobe hemisection in comparison to the rats that underwent sham irradiation following sham brain surgery in a study evaluating the timing of irradiation following brain surgery. At 24 h following irradiation or sham irradiation, the rats that underwent irradiation at 10 days following brain surgery and the rats that underwent irradiation at 20 days following brain surgery had significantly increased mean MDA levels as compared to the rats that underwent sham irradiation following sham brain surgery [21]. In a study evaluating melatonin as a protectant against the oxidant injury induced by irradiation, Bhatia and Manda compared the GSHPX activities in the brain in the mice that underwent irradiation in a single fraction of 6 Gy in comparison to the mice that underwent sham irradiation.…”

The Effect of Timing of Concurrent Chemoradiation in Patients With Newly Diagnosed Glioblastoma

“…18 Rat model studies have demonstrated higher levels of brain injury with early initiation of radiation. 19 …”

Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line?

“…If similar trends are corroborated in post-hoc analyses of patients who were treated by irradiation combined with temozolomide then consideration should be given to a trial design that compares moderate-length intervals between surgery and irradiation to earlier initiation of treatment (e.g., 5 vs. 2 weeks). The biological rationale for this concept is available [51], but does the equipoise exist to mount such an effort? Fig.…”