[citation needed] Unfortunately for some patients, as time passes, people who received radiation therapy may begin experiencing deficits in their learning, memory, and spatial information processing abilities.
[1] To test this proposal, a group of rats with normal hippocampal neurogenesis (control) were subjected to a placement recognition exercise that required proper hippocampus function to complete.
[4] A 2004 cohort study concluded that irradiation of the brain with dose levels overlapping those imparted by computed tomography can, in at least some instances, adversely affect intellectual development.
[5][6] Radiation therapy at doses around "23.4 Gy" was found to cause cognitive decline that was especially apparent in young children who underwent the treatment for cranial tumors, between the ages of 5 and 11.
[7] Radiation of 100 mGy to the head at infancy resulted in the beginning appearance of statistically significant cognitive-deficits in one Swedish/radiation-therapy follow-up study.
[5] Radiation of 1300-1500mGy to the head at childhood was similarly found to be roughly the threshold dose for the beginning increase in statistically significant rates of schizophrenia.
[8] From soliciting for participants in a study and then examination of the prenatally exposed at Hiroshima & Nagasaki, those who experienced the prompt burst of ionizing radiation at the 8-15 and 16–25 week periods after gestation were to, especially in the closest survivors, have a higher rate of severe mental retardation as well as variation in intelligence quotient (IQ) and school performance.
[9][8] Adult humans receiving an acute whole body incapacitating dose (30 Gy) have their performance degraded almost immediately and become ineffective within several hours.
At this time they begin exhibiting symptoms of radiation poisoning of sufficient severity to render them totally ineffective.
[8] Cumulative equivalent doses above 500 mSv of ionizing radiation to the head, were proven with epidemiological evidences to cause cerebrovascular atherosclerotic damage, thus increasing the chances of stroke in later life.
Animal studies have been performed by Monje and Palmer to determine if there is an acute ablation of the stem cell pool.
One month after the reception of the dosage, living precursor cells from these rats’ hippocampus were successfully isolated and cultured.
The results indicated that the irradiated culture contained a higher number of differentiated neuron and glial cells in comparison to the control.
The results show that stem cell survival was similar to that found in a control subject (normal rat hippocampus); however, the number of neurons generated was decreased by 81%.
[15] Therefore, focusing on the microglial activation, inflammatory response, and microvasculature may produce a direct link to the decrease in neurogenesis post irradiation.
Radiation therapy usually results in chronic inflammation, and in the brain this inflammatory response comes in the form of activated microglia cells.
To investigate this concept, an animal study was performed by Monje et al. in order to determine the specific cytokines or stress hormones that were released by activated microglial cells that decrease neurogenesis in an irradiated hippocampus.
A second study was also performed to ensure that the decrease in neurogenesis was the result of released cytokines and not cell-to-cell contact of microglia and stem cells.
The results of this study indicated that neurogenesis also showed a similar decrease in the preconditioned media culture versus the control.
[17] The microvasculature of the subgranular zone, located in dentate gyrus of hippocampus, plays an important role in neurogenesis.
Specifically, disruption of the cluster/vessel association in the subgranular zone of the dentate gyrus and cytokines released by activated microglia as part of the inflammatory response do impair neurogenesis in the irradiated hippocampus.
However, in this study the inflammatory response was not eliminated entirely, and some cytokines or stress hormones continued to be secreted by the remaining activated microglia cells causing the reduction in neurogenesis.
This study focused mainly on the c-Jun NH2 – terminal kinase pathway which when activated results in the apoptosis of neurons.
In the study, the JNK was inhibited using 5 μM SP600125 dosage, and this resulted in a decrease of neural stem cells apoptosis.
It has already been shown by Elodie Bruel-Jungerman et al. that subjecting animals to learning exercises that are heavily dependent on the hippocampus results in increased neurogenesis.