Therapeutic hypothermia is limited in preventing developmental impairments after neonatal hypoxia-ischemia.

The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats. In P7, animals were submitted to right common carotid artery occlusion followed by hypoxia (8% oxygen). TH was performed by reducing the animal scalp temperature to 32°C for 5 h. Behavioral parameters and developmental landmarks were evaluated. Animals were euthanized at P9 or P21, and cerebral hemispheres, spleen, and thymus were weighed. White blood cells (WBC) were counted in blood smears. There was a reduction in the weight of the brain hemisphere ipsilateral to the carotid occlusion in HI and TH groups, as well as a reduction in body weight gain and a delay in the opening of the ipsilateral eye. Latency in negative geotaxis was increased by HI at P12. TH did not prevent brain weight loss, developmental impairments, or WBC number changes but prevented negative geotaxis impairment and spleen weight reduction. These data reinforce that a better understanding of the events that occur after HI and TH in both males and females is necessary and would allow the development of more adequate and sex-specific therapeutic approaches.

Short-term effects of therapeutic hypothermia following hypoxia-ischemia in neonatal male and female rats.

Nowadays, the only treatment for human babies suffering from hypoxia-ischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI. Seven-day-old Wistar rats underwent a surgery for unilateral occlusion of the right common carotid artery and were exposed to a hypoxic atmosphere (8% oxygen) for 75 min. Then, the animals in the TH group were submitted to TH (scalp temperature of 32°C) for 5 h. In the behavioral tests, no remarkable differences triggered by HI or TH were observed relative to SHAM animals. Only females of the HI group presented lower latency to complete the righting reflex test. TH reduced the volume of brain injury in males, but not in females. The animals of the HI group showed a reduction in the number of neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus and TH partially prevented neuronal death. In the CA1 region of the hippocampus, animals from the HI group showed more degenerating cells relative to the SHAM, which was reversed by TH. In the DG, animals from the HI group showed an increase in the number of degenerating neurons, which was partially reversed by TH only in males. Our data show that HI leads to a brain injury, which was attenuated by TH in a sex-dependent way and clarify the importance of the assessment of males and females in order to outline specific strategies for the treatment of each sex in newborns suffering from HI.

The role of FASL, BCL-2 and BAX polymorphisms in brazilian patients with prostate cancer and benign prostatic hyperplasia.

BACKGROUND: Prostate cancer (PCA) is one of the leading causes of death among men, being related to several factors, including the aging male population, like benign prostatic hyperplasia (BPH), a histopathological and hyperplastic alteration associated to prostate aging. The FASL, BCL-2 and BAX genes are involved in cell apoptosis regulation and can be related to the development of both cancer and hyperplasia. This study aimed to investigate the association of FASL - 844 (rs763110), BCL-2 -938 (rs2279115) and BAX - 248 (rs4645878) polymorphic variants in Southern Brazilian PCA and BPH patients and healthy controls. METHODS AND RESULTS: 348 samples were analyzed, being 123 from PCA patients, 143 BPH patients and 82 healthy controls, using PCR-RFLP techniques. The results of genotyping analysis were adjusted by age, and compared with PSA levels and prostate volume. The analyzes of genotype frequencies according to PCA, HPB and controls, were performed by logistic regression corrected by age, and showed that the FASL CC genotype can be a risk factor for PCA patients, when compared to controls (p = 0.041). The clinical data investigation indicated higher PSA levels in PCA patients with FASL CC genotype, as compared to TC genotype carriers (p = 0.044), higher PSA levels for healthy individuals with BCL-2 AA genotype, comparing with CC genotype (p = 0.027) and higher PSA levels in BPH group with FASL CC genotype, as compared to TC genotype (p = 0.044). CONCLUSIONS: Our data indicate the FASLCC genotype as a risk factor for prostate pathologies, whileBCL-2 CC can act as a protective genotype.