title: Hippocampal-dependent neurocognitive impairment following cranial irradiation observed in pre-clinical models: current knowledge and possible future directions.
abstract: We reviewed the literature for studies pertaining to impaired adult neurogenesis leading to neurocognitive impairment following cranial irradiation in rodent models. This compendium was compared with respect to radiation dose, converted to equivalent dose in 2 Gy fractions (EQD2) to allow for direct comparison between studies. The effects of differences between animal species and the dependence on animal age as well as for time after irradiation were also considered. One of the major sites of de novo adult neurogenesis is the hippocampus, and as such, this review also focuses on assessing evidence related to the expression and potential effects of inflammatory cytokines on neural stem cells in the subgranular zone of the dentate gyrus and whether this correlates with neurocognitive impairment. This review also discusses potential strategies to mitigate the detrimental effects on neurogenesis and neurocognition resulting from cranial irradiation, and how the rationale for these strategies compares with the current outcome of pre-clinical studies.
authors.affiliation: 1 Institute for Onco-Physics, Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.|2 Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA.|3 Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tomé
authors.affiliation: 3 Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Şölen
authors.initials: Ş
authors.lastname: Gökhan
authors.affiliation: 4 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Gulinello
authors.affiliation: 1 Institute for Onco-Physics, Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.|2 Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: N Patrik
authors.initials: NP
authors.lastname: Brodin
authors.affiliation: 2 Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: John
authors.initials: J
authors.lastname: Heard
authors.affiliation: 3 Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.|4 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.|5 Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Mehler
authors.affiliation: 1 Institute for Onco-Physics, Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.|2 Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects*; D003072:Cognition Disorders / Q000209:etiology*; D016371:Cranial Irradiation / Q000009:adverse effects*; D006624:Hippocampus / Q000528:radiation effects*; D055495:Neurogenesis / Q000528:radiation effects; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000150:complications*; D051381:Rats