Background and Purpose: Neonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of death and disability in newborns. Clinical and experimental studies suggest a sexual dimorphism in HI-induced brain injury and therapy responses. A major hallmark of HI pathophysiology is the infiltration of peripheral immune cells into the injured brain. However, the specific role of regulatory T cells (Tregs) in neonatal HI is still unknown. Methods: Nine-day-old mice were exposed to HI by ligation of the right common carotid artery followed by 1 hour hypoxia (10% oxygen). Using immunohistochemistry, flow cytometry, and microarray analyses, Tregs were investigated in the brain, spleen, and blood 24 hours post HI. The functional role of Tregs was evaluated by acute Treg depletion in depletion of regulatory T cells transgenic mice. Brain injury, neuroinflammatory responses, and vascular injury were analyzed via immunohistochemistry and Western blot 48 hours and 7 days after HI. Functional outcome was assessed 3 days and 5 weeks after HI. Results: Female mice revealed an increased cerebral Treg infiltration, coinciding with elevated chemokine receptor expression. Treg depletion in females aggravated HI-induced brain tissue injury, short-term motor deficits, and long-term deficits in exploratory activity, paralleled by an increased microglia and endothelial activation and leukocyte infiltration. Treg depletion in male mice reduced HI-induced brain injury, short-term motor, and long-term cognitive deficits, associated with reduced vascular injury. Ex vivo isolated female Tregs displayed an increased immunosuppressive activity on effector T cell proliferation and an increased gene enrichment in pathways related to enhanced Treg activity. Conclusions: Tregs from neonatal female mice provide endogenous neuroprotection, whereas Tregs from male mice increase secondary neurodegeneration. As potential mechanisms, we identified intrinsic transcriptional differences associated with enhanced anti-inflammatory activity of female Tregs. Our study emphasizes the urgent need for sex-stratified clinical and preclinical analyses.

(1) This study investigated the whitening effect, cytotoxicity and enamel surface alterations induced by different over-the-counter (OTC) bleaching agents in comparison to hydrogen peroxide. (2) Human teeth (n = 60) were randomly assigned into 6 groups (n = 10), stained with coffee solution for 7 d, followed by a whitening period of 7 d with either placebo, bromelain, sodium bicarbonate, sodium chlorite, PAP or hydrogen peroxide. Color measurements were performed with a spectrophotometer. Scanning electron micrographs (SEM) were taken to assess the enamel structure. Cytotoxicity of the tested substances was assessed based on the cell viability of primary human fibroblasts. (3) The application of all whitening gels resulted in a greater color difference of the enamel (ΔE) in comparison to the negative control. Hydrogen peroxide caused the greatest color difference. Bromelain and PAP treatment showed no enamel surface changes, in contrast to hydrogen peroxide treatment, which showed very mild interprismatic dissolution. Bromelain was the only non-cytotoxic agent. (4) The maximum effect achieved by all OTC bleaching agents was the removal of stains, whereas hydrogen peroxide was capable of further whitening the teeth. Bromelain treatment was neither cytotoxic, nor resulted in enamel surface alterations, and its whitening effect was less, yet still effective, compared to hydrogen peroxide.

Ion fluxes across the inner mitochondrial membrane control mitochondrial volume, energy production, and apoptosis. TMBIM5, a highly conserved protein with homology to putative pH-dependent ion channels, is involved in the maintenance of mitochondrial cristae architecture, ATP production, and apoptosis. Here, we demonstrate that overexpressed TMBIM5 can mediate mitochondrial calcium uptake. Under steady-state conditions, loss of TMBIM5 results in increased potassium and reduced proton levels in the mitochondrial matrix caused by attenuated exchange of these ions. To identify the in vivo consequences of TMBIM5 dysfunction, we generated mice carrying a mutation in the channel pore. These mutant mice display increased embryonic or perinatal lethality and a skeletal myopathy which strongly correlates with tissue-specific disruption of cristae architecture, early opening of the mitochondrial permeability transition pore, reduced calcium uptake capability, and mitochondrial swelling. Our results demonstrate that TMBIM5 is an essential and important part of the mitochondrial ion transport system machinery with particular importance for embryonic development and muscle function.

Cochlear implants (CIs) are the primary treatment method in patients with profound sensorineural hearing loss. Interpretation of postoperative imaging with conventional energy-integrating detector computed tomography (EID-CT) following CI surgery remains challenging due to metal artifacts. Still, the photon-counting detector (PCD-CT) is a new emerging technology with the potential to eliminate these problems. This study evaluated the performance of virtual monoenergetic (VME) EID-CT images versus PCD-CT in CI imaging. In this cadaveric study, two temporal bone specimens with implanted CIs were scanned with EID-CT and PCD-CT. The images were assessed according to the visibility of interelectrode wire, size of electrode contact, and diameter of halo artifacts. The visibility of interelectrode wire sections was significantly higher when reviewing PCD-CT images. The difference in diameter measurements for electrode contacts between the two CT scanner modalities showed that the PCD-CT technology generally led to significantly larger diameter readings. The larger measurements were closer to the manufacturer’s specifications for the CI electrode. The size of halo artifacts surrounding the electrode contacts did not differ significantly between the two imaging modalities. PCT-CT imaging is a promising technology for CI imaging with improved spatial resolution and better visibility of small structures than conventional EID-CT.

A synaptic sexual dimorphism is relevant in the context of multiple neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Many of these disorders show a different prevalence and progression in woman and man. A similar variance is also present in corresponding animal models. To understand and characterize this dimorphism in pathologies it is important to first understand sex differences in unaffected individuals. Therefore, sexual differences have been studied since 1788, first focusing on brain weight, size, and volume. But as these measures are not directly related to brain function, the investigation of sexual dimorphism also expanded to other organizational levels of the brain. This review is focused on sexual dimorphism at the synaptic level, as these specialized structures are the smallest functional units of the brain, determining cell communication, connectivity, and plasticity. Multiple differences between males and females can be found on the levels of spine density, synaptic morphology, and molecular synapse composition. These differences support the importance of sex-disaggregated data. The specificity of changes to a particular brain region or circuit might support the idea of a mosaic brain, in which each tile individually lies on a continuum from masculinization to feminization. Moreover, synapses can be seen as the smallest tiles of the mosaic determining the classification of larger areas.

The proper preservation of human brain tissue is an indispensable requirement for post-mortem investigations. Neuroanatomical teaching, neuropathological examination, neurosurgical training, basic and clinical neuroscientific research are some of the possible downstream applications of brain specimens and, although much apart from one another, proper tissue fixation and preservation is a common denominator to all of them. In this review, the most relevant procedures to fixate brain tissue are described. In situ and immersion fixation approaches have been so far the most widespread ways to deliver the fixatives inside the skull. Although most of them rely on the use of formalin, alternative fixative solutions containing lower amounts of this compound mixed with other preservative agents, have been attempted. The combination of fixation and freezing paved the way for fiber dissection, particularly relevant for the neurosurgical practice and clinical neuroscience. Moreover, special techniques have been developed in neuropathology to tackle extraordinary problems, such as the examination of highly infective specimens, as in the case of the Creutzfeldt-Jakob encephalopathy, or fetal brains. Fixation is a fundamental prerequisite for further staining of brain specimens. Although several staining techniques have been developed for the microscopical investigation of the central nervous system, numerous approaches are also available for staining macroscopic brain specimens. They are mostly relevant for neuroanatomical and neuropathological teaching and can be divided in white and gray matter staining techniques. Altogether, brain fixation and staining techniques are rooted in the origins of neuroscience and continue to arouse interest in both preclinical and clinical neuroscientists also nowadays.