Neurobiological responses to stereotactic focal irradiation of the adult rodent hippocampus

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.

The Hippocampus Sparing Volume Modulated Arc Therapy does not Influence Plan Quality on Locally Advanced Nasopharyngeal Carcinoma Patients

“…But such radiotherapeutic plans were also reported to have severe side effects, especially on neuro-cognition of memory and social understanding. Later studies 3 , 4 revealed that it was the radiation damage on hippocampus during radiotherapy that caused neuro-cognitive dysfunction.…”

“…Yet this radiotherapeutic strategy was reported to present severe side effects of a decline in memory and social understanding after treatment 3 . And such neuro-cognitive dysfunction was later found out to be attributed to radiation damage on the hippocampus dentate gyrus caused by radiation treatment 4 . However, intensity modulated radiation therapy (IMRT) 5 , including Volumetric Modulated Arc Therapy (VMAT) 6 , 7 , has been widely used in NPC patients.…”