Effects of radiotherapy on the hippocampus and hippocampal neurogenesis: a systematic review of preclinical studies.

in Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] by Sandra Leskinen, Samir Alsalek, A Gabriella Wernicke

TLDR

  • The study reviewed 90 animal studies to understand the effects of cranial radiotherapy on hippocampal neurogenesis and identified potential protective strategies to mitigate these effects.
  • Cranial irradiation reduces hippocampal neurogenesis, causes molecular alterations, and induces inflammation, leading to cognitive deficits.

Abstract

A comprehensive literature review was undertaken to understand the effects and underlying mechanisms of cranial radiotherapy (RT) on the hippocampus and hippocampal neurogenesis as well as to explore protective factors and treatments that might mitigate these effects in preclinical studies. PubMed/MEDLINE, Web of Science, and Embase were queried for studies involving the effects of radiation on the hippocampus and hippocampal neurogenesis. Data extraction followed the Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines, and a risk of bias assessment was conducted for the included animal studies using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. Ninety studies were included, with 48 assessing radiation-induced changes and 42 examining possible interventions. The majority of studies (97.8%) used experimental animal models. Studies demonstrated that cranial irradiation reduces hippocampal neurogenesis, particularly in the neurogenic niches of the dentate gyrus; causes alterations in gene expression and enzymatic activity; induces inflammation; promotes apoptosis; and often results in cognitive impairment. Potential protective strategies include pharmacological agents like metformin and peroxisome proliferator-activated receptor-α (PPAR-α) agonists or behavioral interventions like voluntary running. In a risk of bias assessment, many studies were rated as having an unclear risk of bias. Radiotherapy, while essential for managing brain tumors, can have adverse effects on hippocampal function and structure in animal models. These effects manifest in reduced neurogenesis, molecular alterations, and increased inflammation, leading to cognitive deficits. Further research is needed to identify and improve interventions and develop comprehensive therapeutic approaches that balance effective tumor control with the preservation of cognitive health.

Overview

  • The study aimed to investigate the effects of cranial radiotherapy (RT) on the hippocampus and hippocampal neurogenesis, as well as explore protective factors and treatments to mitigate these effects.
  • The study included 90 animal studies, with 48 assessing radiation-induced changes and 42 examining possible interventions, using a range of experimental animal models.
  • The study aimed to identify potential protective strategies, including pharmacological agents and behavioral interventions, to preserve cognitive health and balance tumor control with hippocampal function and structure.

Comparative Analysis & Findings

  • Cranial irradiation reduces hippocampal neurogenesis, particularly in the neurogenic niches of the dentate gyrus, and causes alterations in gene expression and enzymatic activity.
  • Studies demonstrated that radiation induces inflammation, promotes apoptosis, and often results in cognitive impairment, highlighting the adverse effects of radiotherapy on hippocampal function and structure.
  • Potential protective strategies identified include pharmacological agents such as metformin and peroxisome proliferator-activated receptor-α (PPAR-α) agonists, as well as behavioral interventions like voluntary running.

Implications and Future Directions

  • Further research is needed to identify and improve interventions to balance effective tumor control with the preservation of cognitive health.
  • A comprehensive therapeutic approach should be developed, taking into account the risks and effects of radiotherapy on hippocampal function and structure.
  • Elucidating the underlying mechanisms of radiation-induced hippocampal damage and identifying novel therapeutic targets may aid the development of effective treatments.
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