Early effects of 16O radiation on neuronal morphology and cognition in a murine model.

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

Very low doses of heavy oxygen ion radiation induce premature ovarian failure.

Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET = 179 keV/µm). Adult female mice were irradiated with 0, 5, 30 or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA). Six-hour after irradiation, percentages of ovarian follicles immunopositive for γH2AX, a marker of DNA double strand breaks, 4-HNE, a marker of oxidative lipid damage and BBC3 (PUMA), a proapoptotic BCL-2 family protein, were dose dependently increased in irradiated mice compared to controls. One week after irradiation, numbers of primordial, primary and secondary follicles per ovary were dose dependently decreased, with complete absence of follicles in the 50 cGy groups. The ED50 for primordial follicle destruction was 4.6 cGy for oxygen compared to 27.5 cGy for iron in our previous study. Serum FSH and LH concentrations were significantly elevated in 50 cGy groups at 8 week. Supplementation with ALA mitigated the early effects, but not the ultimate depletion of ovarian follicles. In conclusion, oxygen charged particles are even more potent inducers of ovarian follicle depletion than charged iron particles, raising concern for premature ovarian failure in astronauts exposed to both particles during space travel.

Metabolic changes after H(2) 15O-positron emission tomography with acetazolamide in a patient with moyamoya disease: case report and review of previous cases.

Perioperative ischemic complications not directly related to surgery require special attention in patients with moyamoya disease; positron emission tomography (H(2) 15O-PET) and single-photon emission computed tomography have been considered indispensable for evaluating pre- and postsurgical cerebral hemodynamics. The clinical records of 14 patients with moyamoya disease who underwent 26 extracranial-intracranial bypass operations were reviewed with special reference to perisurgical complications. One patient developed multiple postoperative ischemic infarctions and died of ischemic brain edema. The history of this patient with prolonged acidosis is analyzed, and the role of metabolic changes induced by H(2) 15O-PET with acetazolamide challenge is reviewed. Seven (77.8%) of nine patients operated on within 48 hours after H(2) 15O-PET with acetazolamide (group 1) developed metabolic acidosis, whereas only three (17.6%) of 17 patients operated on >48 hours (group 2) after the examination had intraoperative pH of <7.35. In group 1, the mean intraoperative pH was 7.328, which was significantly lower than the mean pH of 7.393 (P <.0001) in group 2. After H(2) 15O-PET with acetazolamide challenge, patients must be carefully observed concerning acidosis and volume state. We recommend at least 48 hours between examination and surgery for patients with moyamoya disease so that their conditions can stabilize. Furthermore, special care should be taken to avoid additional perioperative risk factors such as hypotension, hypocapnia, hypercapnia, and hypovolemia.

Morphological changes in rat's brain choroid plexus after exposure to low doses of high energy oxygen ions, fast neutrons, and gamma radiation.

Ultrastructural and morphometrical changes in choroid plexus cells of the rat's brain in the delay period after irradiation with low doses of oxygen ions [= 300 MeV/nucleon], and fast neutrons [1.5 MeV], and gamma rays (Co60) were described. The applied irradiations provoked similar ultrastructural changes in choroid plexus cells; however, the obtained morphometrical data showed differing effects of these radiations, due to, probably, different mechanisms of their effect on the cells.