Treatment of brain tumors may require irradiation of the head, which can result in damage to the brain with long term mental and physical problems. Irradiation has been identified as causing apoptosis (a natural form of cell death) and loss of neurogenesis (growth of new brain cells) in a specific layer of the hippocampus (an anatomical area of the brain).This damage can occur with even low doses of irradiation.
The hippocampus of the brain is most effected by radiation damage and is important for learning, memory, and spatial processing. The evidence at this time indicates that irradiation damages the progenitor cells from which new brain cells are developed. Little damage is seen in areas of the brain outside the hippocampus.
Previous studies with chemical neurotoxins have shown that lithium has a protective effect on the nervous system. Lithium has to be given for 2 or 3 days for protection to develop and reaches maximum protection after 6 or 7 days of treatment. Maximal protection is reached at 100 mg./kg.
The current study by the authors was done to study the neuroprotective effect of lithium against irradiation damage. The damage was tested by following changes in gene and protein expression before and after hippocampal irradiation in rats. Also, the rats were studied for their ability to learn. Slides of the rat’s brains were studied for irradiation changes. Live brain cells were studied for their ability to grow after irradiation.
The studies showed that irradiation of the newborn rat brain resulted in problems with spatial navigation, probably due to damage to hippocampus. The females showed more cognitive damage than the males. The animals that had been pretreated with lithium chloride (LiCl) showed less difficulty with spatial navigation. Previous studies have shown that LiCl has no effect on the growth of cancer cells.
LiCl pretreatment resulted in a 2-fold increase in the genes that block apoptosis, increase DNA repair and increase neurogenesis.
CONCLUSION: The authors demonstrated in this study that lithium is protective of the hippocampus of the brain if given before a patient is to be given cranial irradiation. Even small doses of irradiation resulted in hippocampal damage. The authors believe that LiCl works by protecting the brain from apoptosis by modulation of the genes that regulate apoptosis.
This information may be important in protecting patients from the long term cognitive damage from brain irradiation. Females are more at risk for this damage than males. The adequate dose for maximal benefit seemed to be between 40 and 80 mg./kg. for seven days before irradiation.
To read the author’s abstract of the article click on the link to the author’s title of the article above.