Radiation-induced interference with postnatal hippocampal cytogenesis in rats and its long-term effects on the acquisition of neurons and glia

1975 ◽  
Vol 163 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Shirley A. Bayer ◽  
Joseph Altman
2020 ◽  
Author(s):  
Syed Mohammed Musheer Aalam ◽  
Ishaq A. Viringipurampeer ◽  
Matthew C. Walb ◽  
Erik J. Tryggestad ◽  
Chitra P. Emperumal ◽  
...  

AbstractChronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic hyposalivation continues to be a challenge that causes long-term health implications resulting in compromised quality of life. Recent advances in salivary stem cell research promise new frontier in the treatment of radiation-induced hyposalivation by initiating regeneration of radiation-damaged salivary parenchymal cells. Lack of a standard preclinical immunodeficient model to assess radiation-induced changes objectively and quantitatively in salivary flow rates will impede rapid progress towards the development of cellular therapies for chronic salivary dysfunction and attendant xerostomia. Herein, we report the first fully characterized novel cone-beam computed tomography (CBCT)-guided precision ionizing radiation (IR) induced chronic hyposalivation model in radiosensitive, immunodeficient transgenic NSG-SGM3 mice expressing three human cytokines including c-KIT ligand/stem cell factor. Additionally, we also report a novel and instantaneous method to objectively assess the kinetics of pilocarpine-stimulated salivary flowrate. Comprehensive structural and functional characterization of salivary glands revealed previously unknown and highly complex gender, age, IR dose and salivary gland subtype-specific effects of salivary-ablative precision IR.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi161-vi161
Author(s):  
Dorela Shuboni-Mulligan ◽  
Demarrius Young Jr. ◽  
Julianie De La Cruz Minyety ◽  
Nicole Briceno ◽  
Amanda King ◽  
...  

Abstract BACKGROUND Disrupted sleep, including daytime hypersomnolence, is a core symptom reported by primary brain tumor patients and often manifests after radiotherapy. The biological mechanisms driving cranial radiation-induced hypersomnolence (C-RIH) remain unclear but we hypothesize this may result from damage to neural circuits controlling sleep behavior. We developed a mouse model of C-RIH to explore the impact of radiation on the brain: examining region-specific differences in acute DNA damage response and neuroanatomic structure. METHODS Mice received whole brain radiation then behaviors were monitored using PhenoTyper® cages to determine optimal dose and long-term effects. To test short-term neurologic effects, brains were collected 1hr post-radiation then stained for γH2AX, a signal for DNA damage. Long-term effects were quantified 1-month post-treatment using neuroimaging to determine brain volume and T1 mapping changes in regions associated with sleep, circadian rhythms, and cognition. RESULTS Mice displayed decreased general activity and increased daytime sleep in a dose-dependent and sustained manner. Histologic staining demonstrated that DNA damage following radiation varies across the brain, with homeostatic sleep regions and cognitive regions expressing higher levels of γH2AX than the circadian suprachiasmatic nucleus. These findings were supported by in vitro studies comparing radiation effects in SCN and cortical astrocytes using both trypan blue (F(1,18)=235.937, p< 0.001) and clonogenic assays (F(1,24)=40.796, < 0.001). Brain volumes were significantly smaller in irradiated than sham animals in the hippocampus (t(4)=3.833, p=0.019) and the pontine central grey (t(4)=3.504, p=0.025). T1 maps also showed significant changes in relaxation times in many cognitive regions but not sleep or circadian areas. CONCLUSIONS These findings suggest that the homeostatic sleep region and cognitive circuits are vulnerable to radiation and may be relevant to the development of treatment plans in patients. We plan to introduce intracranial tumor to the model to evaluate the impact of timing of treatment and C-RIH on survival.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 695-695
Author(s):  
Melissa Frick ◽  
Carolyn Vachani ◽  
Margaret K. Hampshire ◽  
Christina Bach ◽  
Karen Arnold-Korzeniowski ◽  
...  

695 Background: There is significant need for quality follow-up care to optimize long-term outcomes for the growing population of lower gastrointestinal (GI) cancer survivors. Patient-reported outcomes (PROs) provide valuable information regarding late- and long-term effects. Methods: Using a convenience sample from 1,129 colon, rectal and anal cancer survivors (n=792, 218, and 119, respectively) who utilized an Internet-based survivorship care plan (SCP) tool, we examined patient-reported demographics, treatment, and toxicity data. Responses from a follow-up survey were reviewed. Results: Median age of diagnosis was 51 years and median current age was 54 years. 81% of respondents were Caucasian and 58% were female. The most commonly reported late- and long-term effects for all survivors were neuropathy (65%), fatigue (56%), cognitive changes (49%), changes in GI function (43%), sexual dysfunction (22% in males, 43% in females), and radiation-induced dermatologic effects including changes in color/texture of skin (39%) and loss of flexibility in radiated areas (31%). The prevalence of these effects varied with length of time since treatment and treatment modality. Anal cancer patients reported a high prevalence of sexual dysfunction and radiation-induced dermatologic effects. Over 87% of users reported satisfaction levels of "good" to "excellent" using this tool, and 69% reported they intend to share SCP with their healthcare team. Conclusions: For lower GI cancer survivors, it is feasible to obtain PROs from an Internet-based survivorship tool. Survivors report a wide spectrum of late- and long-term side effects, which can be used to inform counseling at time of diagnosis, as well as help anticipate and respond to disease- and treatment-related sequelae during follow-up. We are among the first to report on PROs in anal cancer survivors. Further investigation on the impact of SCPs on healthcare communication and use is needed.


2016 ◽  
Vol 38 (4) ◽  
pp. 219-223 ◽  
Author(s):  
E A Domina

Among the long-term effects of the Chornobyl disaster the greatest concern of international medical and scientific community is given to the established fact of excess of the spontaneous level of cancer incidence in the exposed population. According to modern concepts, the accumulation of chromosome aberrations, especially in radiosensitive cells, could be potentially oncogenic, and low doses of ionizing radiation could be promoters of the radiation-induced carcinogenesis. The results of our studies have shown that such substances as thymalin, inosine, ascorbic acid, caffeine could modify radiation-induced cytogenetic effects in peripheral blood lymphocytes of healthy individuals and exert protective or sensitizing action dependent on their concentrations, cell radiosensitivity, dose of irradiation, and relative biologic effectiveness of ionizing radiation. This article is part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.


Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.


Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


2012 ◽  
Vol 43 (3) ◽  
pp. 42
Author(s):  
MITCHEL L. ZOLER
Keyword(s):  

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