Early postnatal irradiation‐induced age‐dependent changes in adult mouse brain: MRI based characterization

Abstract

Background Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis. Results We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10. Conclusions The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

“…injury. In fact, P3 mouse cerebellum is comparable to the human gestational period of 2 23 weeks, a rapid developmental growth phase characterized by extreme radiosensitiv compared to other brain structures [40]. Moreover, bystander DNA double-strand brea (DSBs) and apoptosis have previously been detected by our group in the shielded ce bellum of PBI mice at P2, indicating transmission of radiation injury from the expos distal third of the body to the brain [41].…”

“…Furthermore, to understand how radiation-induced changes in the miRNA and protein exosomes cargo influence the stress response of distant cells by propagating either damaging or protective signals, we applied an in vivo functional assay interrogating the cerebellum of neonatal mice at postnatal day 3 (P3), highly susceptible to radiation injury. In fact, P3 mouse cerebellum is comparable to the human gestational period of 22-23 weeks, a rapid developmental growth phase characterized by extreme radiosensitivity compared to other brain structures [40]. Moreover, bystander DNA double-strand breaks (DSBs) and apoptosis have previously been detected by our group in the shielded cerebellum of PBI mice at P2, indicating transmission of radiation injury from the exposed distal third of the body to the brain [41].…”

Cross-translational models of late-onset cognitive sequelae and their treatment in pediatric brain tumor survivors

“…Longitudinal MRI through development in a mouse model of cranial radiation shows widespread volume loss is induced early after radiation treatment and affects the white matter more significantly than the gray matter (Ayoub et al, 2021;Gazdzinski et al, 2012). Consistent with clinical risk factors, decreased radiation doses and later ages at irradiation produce smaller volume changes (de Guzman et al, 2015;Ren et al, 2021). Manipulation of radioresponse, by knockout of p53 to reduce apoptosis for instance, alters the degree of volume loss (de Guzman et al, 2019), which can act as a valuable surrogate for cognition and behavior outcomes in early phases of research (Ellegood et al, 2013).…”

Anemia ‐ an initial manifestation of Bing‐Neel syndrome: A case report

“…Primary Waldenström macroglobulinemia (WM) is a rare disease of unknown etiology, with an annual incidence of about 3/1 million. [ 1 ] Hyperviscosity manifests as cerebral infarction caused by monoclonal immunoglobulinm (IgM) protein in the blood. [ 2 ]…”

“…Primary Waldenström macroglobulinemia (WM) is a rare disease of unknown etiology, with an annual incidence of about 3/1 million. [1] Hyperviscosity manifests as cerebral infarction caused by monoclonal immunoglobulinm (IgM) protein in the blood. [2] Clinical manifestations: Patients may develop symptoms associated with infiltration of hematopoietic or other tissues (such as anemia, lymphadenopathy, hepatosplenomegaly), or symptoms associated with monoclonal IgM protein in the blood (such as hyperviscosity, peripheral neuropathy).…”