Numerous studies provide increasing evidence, which supports the ideas that every cell in the brain of males may differ from those in females due to differences in sex chromosome complement as well as in response to hormonal effects. In this study, we address the question as to whether actions of neurosteroids, thus steroids, which are synthesized and function within the brain, contribute to sex-specific hippocampal synaptic plasticity. We have previously shown that predominantly in the female hippocampus, does inhibition of the conversion of testosterone to estradiol affect synaptic transmission. In this study, we show that testosterone and its metabolite dihydrotestosterone are essential for hippocampal synaptic transmission specifically in males. This also holds true for the density of mushroom spines and of spine synapses. We obtained similar sex-dependent results using primary hippocampal cultures of male and female animals. Since these cultures originated from perinatal animals, our findings argue for sex-dependent differentiation of hippocampal neurons regarding their responsiveness to sex neurosteroids up to birth, which persist during adulthood. Hence, our in vitro findings may point to a developmental effect either directly induced by sex chromosomes or indirectly by fetal testosterone secretion during the perinatal critical period, when developmental sexual priming takes place.

Adipose tissue-derived mesenchymal stem cells (ASCs) are a promising stem cell source for cell transplantation. We demonstrate that undifferentiated ASCs display robust oscillations of intracellular calcium [Ca(2+) ](i) which may be associated with stem cell maintenance since oscillations were absent in endothelial cell differentiation medium supplemented with FGF-2. [Ca(2+) ](i) oscillations were dependent on extracellular Ca(2+) and Ca(2+) release from intracellular stores since they were abolished in Ca(2+) -free medium and in the presence of the store-depleting agent thapsigargin. They were inhibited by the phospholipase C antagonist U73,122, the inositol 1,4,5-trisphosphate (InsP(3) ) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) as well as by the gap-junction uncouplers 1-heptanol and carbenoxolone, indicating regulation by the InsP(3) pathway and dependence on gap-junctional coupling. Cells endogenously generated nitric oxide (NO), expressed NO synthase 1 (NOS 1) and connexin 43 (Cx 43). The nitric oxide NOS inhibitors NG-monomethyl-L-arginine (L-NMMA), N(G)-nitro-L-arginine methyl ester (L-NAME), 2-ethyl-2-thiopseudourea, and diphenylene iodonium as well as si-RNA-mediated down-regulation of NOS 1 synchronized [Ca(2+) ](i) oscillations between individual cells, whereas the NO-donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) as well as the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) were without effects. The synchronization of [Ca(2+) ](i) oscillations was due to an improvement of intracellular coupling since fluorescence recovery after photobleaching (FRAP) revealed increased reflow of fluorescent calcein into the bleached area in the presence of the NOS inhibitors DPI and L-NAME. In summary our data demonstrate that intracellular NO levels regulate synchronization of [Ca(2+) ](i) oscillations in undifferentiated ASCs by controlling gap-junctional coupling.

Background and Purpose: Ischemic brain edema can be measured in computed tomography (CT) using quantitative net water uptake (NWU), a recently established imaging biomarker. NWU determined in follow-up CT after mechanical thrombectomy (MT) has shown to be a strong predictor of functional outcome. However, disruption of the blood–brain barrier after MT may also lead to contrast staining, increasing the density on CT scans, and hence, directly impairing measurements of NWU. The purpose of this study was to determine whether dual-energy dual-layer CT (DDCT) after MT can improve the quantification of NWU by measuring NWU in conventional polychromatic CT images (CP-I) and virtual non-contrast images (VNC-I). We hypothesized that VNC-based NWU (vNWU) differs from NWU in conventional CT (cNWU).Methods: Ten patients with middle cerebral artery occlusion who received a DDCT follow-up scan after MT were included. NWU was quantified in conventional and VNC images as previously published and was compared using paired sample t-tests.Results: The mean cNWU was 3.3% (95%CI: 0–0.41%), and vNWU was 11% (95%CI: 1.3–23.4), which was not statistically different (p = 0.09). Two patients showed significant differences between cNWU and vNWU (Δ = 24% and Δ = 36%), while the agreement of cNWU/vNWU in 8/10 patients was high (difference 2.3%, p = 0.23).Conclusion: NWU may be quantified precisely on conventional CT images, as the underestimation of ischemic edema due to contrast staining was low. However, a proportion of patients after MT might show significant contrast leakage resulting in edema underestimation. Further research is needed to validate these findings and investigate clinical implications.

BACKGROUND: Parenchymal hematoma (PH) is a major complication after endovascular treatment (EVT) for ischemic stroke. The hypoperfusion intensity ratio (HIR) represents a perfusion parameter reflecting arterial collateralization and cerebral microperfusion in ischemic brain tissue. We hypothesized that HIR correlates with the risk of PH after EVT. METHODS: Retrospective multicenter cohort study of patients with large vessel occlusion who underwent EVT between 2013 and 2021 at one of the 2 comprehensive stroke centers (University Medical Center Hamburg-Eppendorf, Germany and Stanford University School of Medicine, CA). HIR was automatically calculated on computed tomography perfusion studies as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. Reperfusion hemorrhages were assessed according to the Heidelberg Bleeding Classification. Primary outcome was PH occurrence (PH+) or absence (PH−) on follow-up imaging. Secondary outcome was good clinical outcome defined as a 90-day modified Rankin Scale score of 0 to 2. RESULTS: A total of 624 patients met the inclusion criteria. We observed PH in 91 (14.6%) patients after EVT. PH+ patients had higher HIR on admission compared with PH− patients (median, 0.6 versus 0.4; P <0.001). In multivariable regression, higher admission blood glucose (adjusted odds ratio [aOR], 1.08 [95% CI, 1.04–1.13]; P <0.001), extensive baseline infarct defined as Alberta Stroke Program Early CT Score ≤5 (aOR, 2.48 [1.37–4.42]; P =0.002), and higher HIR (aOR, 1.22 [1.09–1.38]; P <0.001) were independent determinants of PH after EVT. Both higher HIR (aOR, 0.83 [0.75–0.92]; P <0.001) and PH on follow-up imaging (aOR, 0.39 [0.18–0.80]; P =0.013) were independently associated with lower odds of achieving good clinical outcome. CONCLUSIONS: Poorer (higher) HIR on admission perfusion imaging was strongly associated with PH occurrence after EVT. HIR as a surrogate for cerebral microperfusion might reflect tissue vulnerability for reperfusion hemorrhages. This automated and quickly available perfusion parameter might help to assess the need for intensive medical care after EVT.