Protective effect of sex steroid hormones on morphological and cellular outcomes after neonatal hypoxia-ischemia: A meta-analysis of preclinical studies.

Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights the positive effects of these hormones against brain damage induced by neonatal hypoxia-ischemia (HI). This systematic review with meta-analysis aims to verify the efficacy of sex steroid hormones in preventing HI-induced brain damage in rodent models. The protocol was registered at PROSPERO and a total of 22 articles were included. Moderate to large effects were observed in HI animals treated with sex steroid hormones in reducing cerebral infarction size and cell death, increasing neuronal survival, and mitigating neuroinflammatory responses and astrocyte reactivity. A small effect was evidenced for cognitive function, but no significant effect for motor function; moreover, a high degree of heterogeneity was observed. In summary, data suggest that sex steroid hormones, such as progesterone and 17ß estradiol, improve morphological and cellular outcomes following neonatal HI. Further research is paramount to examine neurological function during HI recovery and standardization of methodological aspects is imperative to reduce the risk of spurious findings.

Previous adaptation triggers distinct molecular pathways and modulates early and long-term neuroprotective effects of pregnancy swimming preventing neonatal hypoxia-ischemia damage in rats.

Neonatal hypoxia-ischemia (HI) is one of the main causes of neurological damage in newborns. Pregnancy swimming (PS) alters brain maturation and has neuroprotective effects following HI; however, variables such as timing play a decisive role in its effects. Prior to mating, we tested if adaptation of female rats to a tank filled with water at 32 °C for 7 days before mating, modulates PS benefits. After mating, rats swam 20 min/day or remained in standard cages. Seven-day-old pups were subjected to HI (right common carotid artery occlusion followed by FiO2 8% for 60 min). Animals were divided into 8 experimental groups, adaptation, swimming and injury. Astrocytic reactivity, apoptosis-related proteins, neurotrophins and cell survival markers expression were assessed in the hippocampus 24 h after HI. From PND45, animals performed behavioral tests followed by histological assessment. Three-way ANOVA showed a significant increase in astrogliosis only in non-adapted HI animals. Swimming decreased apoptotic cell death despite adaptation period in both exercised groups. Cylinder evidenced HI impairments; no effect of swimming or adaptation period were observed. In the open field, only HI animals whose mothers had been adapted had increased locomotion; moreover, swimming reversed HI damage. Hemisphere and hippocampus were preserved only in the HI group whose mothers swam before mating, suggesting a preconditioning effect mediated by the adaptation. In summary, adaptation period plays a major role in the mechanisms involving neuroprotection afforded by PS and needs to be further explored in future studies involving damage to the neonatal brain.

Glyceroneogenesis in the hepatopancreas of the crab Neohelice granulata: Diet, starvation and season effects.

We determined the activity of glyceroneogenesis from [2-14C]-pyruvate, the phosphoenolpyruvate carboxykinase activity, [2-14C]-pyruvate oxidation and total lipid levels in the hepatopancreas of the crab Neohelice granulata fed with a carbohydrate-rich (HC) diet or a high-protein (HP) diet and then subjected to 5weeks of starvation, in summer and winter, to determine whether the seasonal adjustments of lipid metabolism to food scarcity are modulated by the composition of the diet previously given to the crabs. The results demonstrated that glyceroneogenesis is an active pathway in N. granulata hepatopancreas, and is regulated by seasonal variations, diet composition and starvation. This study showed that in summer the increase in the hepatopancreas glyceroneogenesis activity is among the strategies used by N. granulata fed an HP diet, to maintain the triglyceride/fatty acid cycle during starvation, a normal condition in the biological cycle of this crab. However, the administration of an HC diet reduced the glyceroneogenesis capacity in response to starvation in summer. In winter, the decrease in the glyceroneogenesis capacity in both fed (HP and HC diets) and starved crabs seems to be a strategy to reduce energy consumption and/or requirement. In contrast to the summer results, the incorporation of [2-14C]-pyruvate into 14CO2 was markedly higher in both diet (HC and HP) groups and in starved crabs during the winter. Four decades after the first study describing the glyceroneogenesis pathway in rat white adipose tissue, this pathway is evidenced for the first time in a crustacean.

N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain.

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.