Exploratory Feasibility Study of Cerebral Cooling by Transpulmonary Cooling During Cardiac Arrest in a Swine Cardiac Arrest Model.

Studies on targeted temperature management for postcardiac arrest syndrome have shown no difference in outcomes between normothermia and hypothermia in patients with postcardiac arrest brain injury. Therefore, further development of therapeutic methods for temperature control in cardiac arrest patients is desirable. Although animal studies have shown that inducing hypothermia during cardiac arrest improves outcomes, no clinically effective method has yet been reported. We investigated whether intra-arrest lung cooling (IALC) effectively lowers brain temperature. A device capable of cooling oxygen was developed. The pigs were subjected to cardiac arrest using the device, ventilated, cooled during cardiopulmonary resuscitation, and resuscitated for 1 hour, with changes in brain temperature closely monitored. A device capable of cooling oxygen to -30°C was used to cool the lungs during cardiac arrest. Through this approach, IALC successfully reduced the brain temperature. Optimal cooling efficiency was observed when chest compressions and ventilation were synchronized at a ratio of 5:1, resulting in an approximate brain temperature reduction of 1.5°C/h. Our successful development of an oxygen-cooling device underscores the potential for lowering brain temperature through IALC using inhaled oxygen cooling.

Impact of altered dietary calcium-phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries.

This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels for a period of 48 days. A marked suppression of body weight gain necessitating humane euthanization occurred on day 28 in rats that had undergone RL and were given high-phosphorus feed. By contrast, the group of intact animals on a high-phosphorus feed exhibited a slightly decreased body weight gain from day 21 and survived until scheduled euthanization. In rats with RL, hematological, blood biochemical, and histopathological analyses demonstrated the presence of CKD-like conditions, particularly in the group that were fed a high-phosphorus diet. Hyperphosphatemia and hypocalcemia were induced by a high-phosphorus diet in both the RL and intact groups, both of which had high levels of FGF23 and parathyroid hormone in the blood. Rats with RL on a high-phosphorus diet showed decreased hematopoiesis by the hematopoietic cell area being narrower in the medullary cavity, proliferation of mesenchymal cells and osteoblasts/osteoclasts, and expansion of the osteoid area, a furthermore generalized vascular lesions, such as calcification, were observed. These findings demonstrate that the partial ligation of the renal arteries combined with a calcium-phosphorus imbalance induced by a high-phosphorus diet serves as an animal model for CKD-like conditions accompanied by bone lesions, helping to elucidate this clinical condition and its underlying molecular mechanisms.

Effect of gonadal steroid hormone levels during pubertal development on social behavior of adult mice toward pups and synaptic transmission in the rhomboid nucleus of the bed nucleus of the stria terminalis.

Sexually immature male mice exhibit parenting behavior toward unfamiliar pups; however, the percentage of males that engage in infanticidal behavior gradually increases with age. We previously reported that excitatory synaptic transmission of the rhomboid nucleus of the bed nucleus of the stria terminalis (BSTrh), a brain region implicated in infanticidal behavior, is reinforced during pubertal development. However, it remains unclear how gonadal steroid hormones mediate this behavioral transition and neural plastic change during pubertal development. Here we revealed that administration of either 17ß-estradiol (E2) or 5α-dihydrotestosterone (DHT) to gonadectomized mice during pubertal development induced infanticidal behavior in adulthood (about 7 weeks old). Next, we performed whole-cell patch clamp recording in the BSTrh to study the effect of gonadal steroid hormones on neural synaptic transmission. We found that E2 but not DHT administration during pubertal development considerably enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of excitatory neurotransmitter release from the presynaptic terminalis. These data suggest that reinforcement of excitatory synaptic transmission by estrogen-receptor-dependent signaling in the BSTrh during puberty may contribute to the development of infanticidal behavior.

Development-dependent behavioral change toward pups and synaptic transmission in the rhomboid nucleus of the bed nucleus of the stria terminalis.

Sexually naïve male C57BL/6 mice aggressively bite unfamiliar pups. This behavior, called infanticide, is considered an adaptive reproductive strategy of males of polygamous species. We recently found that the rhomboid nucleus of the bed nucleus of the stria terminalis (BSTrh) is activated during infanticide and that the bilateral excitotoxic lesions of BSTrh suppress infanticidal behavior. Here we show that 3-week-old male C57BL/6 mice rarely engaged in infanticide and instead, provided parental care toward unfamiliar pups, consistent with observations in rats and other rodent species. This inhibition of infanticide at the periweaning period is functional because the next litter will be born at approximately the time of weaning of the previous litter through maternal postpartum ovulation. However, the mechanism of this age-dependent behavioral change is unknown. Therefore, we performed whole-cell patch clamp recordings of BSTrh and compared evoked neurotransmission in response to the stimulation of the stria terminalis of adult and 3-week-old male mice. Although we were unable to detect a significant difference in the amplitudes of inhibitory neurotransmission, the amplitudes and the paired-pulse ratio of evoked excitatory postsynaptic currents differed between adult and 3-week-old mice. These data suggest that maturation of the synaptic terminal in BSTrh that occurred later than 3 weeks after birth may mediate by the adaptive change from parental to infanticidal behavior in male mice.