Biological characteristics of the cerebral venous system and its hemodynamic response to intracranial hypertension.

BACKGROUND: The role of the cerebral venous system (CVS) in intracranial pressure (ICP) regulation remains largely unclear. In the present study, the interaction between ICP and the cerebral venous system and its possible mechanism were investigated with respect to the biological characteristics of the cerebral venous system and its hemodynamic response under increased ICP. METHODS: We created intracranial hypertension animal model, measured and calculated the venous flow velocity and diameter of the outflow terminal of the CVS with color ultrasonic system and recorded the vascular morphology by 3-dimensional anatomical microscopy. Patients who suffered from raised ICP underwent MRI and digital subtraction angiography (DSA) examination to show the length in the vertical direction of the wall of the bridging vein representing the diameter value. Pathological autopsy was performed from bodies of patients who had died from non-cerebral causes to observe the juncture part between the venous sinuses and tributary vertical brain veins. RESULTS: Under increased ICP conditions, venous drainage through the outlet cuff segment, a unique structure between the bridge vein and sinus, was obstructed and in turn venous blood became congested. Therefore, the increased blood volume worsened the pre-existing ICP according to the well-accepted theory regarding volume-pressure relationship. This phenomenon was described as concurrent "venogenic intracranial hypertension", which is characterized by intracranial venous blood stasis responsive to and together with the original increased ICP. CONCLUSIONS: The existence of this special pathophysiological process is prevalent, rather than rare, in various intracranial disorders. This finding would definitely provide new insight into the area of cerebral venous system research.

Differential expression and regulation of prostaglandin transporter and metabolic enzymes in mouse uterus during blastocyst implantation.

OBJECTIVE: To examine the spatiotemporal expression and regulation of prostaglandin transporter (PGT), 15-hydroxy-PG dehydrogenase (15-PGDH), and carbonyl reductase 1 (CBR1) messenger RNA (mRNA) and protein in the mouse uterus during embryo implantation and in related models. DESIGN: Experimental animal study. SETTING: University research laboratory. ANIMAL(S): Sexually mature female Kunming strain white mice. INTERVENTION(S): Delayed and activated implantation, artificial decidualization, and subcutaneous injection of progesterone (P) and E(2) in ovariectomized mouse. MAIN OUTCOME MEASURE(S): The expression of mRNA and protein were detected by in situ hybridization and immunohistochemistry in mouse uterus. RESULT(S): Prostaglandin transporter mRNA and protein were expressed in the subluminal stroma at implantation site on day 5 of pregnancy and then in decidua but were not detected at the interimplantation sites and in preimplantation or pseudopregnant uterus. The presence of an active blastocyst was required for PGT expression at the implantation site. Both 15-PGDH and CBR1 mRNA were detected in glandular epithelium on day 4 of pregnancies. The expression of 15-PGDH and CBR1 mRNA was also detected in postimplantation embryos. CONCLUSION(S): These data suggest that differentially expressed PGT and 15-PGDH may participate in PG signaling in mouse uterus during implantation and decidualization.

Global analysis of differential luminal epithelial gene expression at mouse implantation sites.

Although implantation types differ between species, the interaction between blastocyst trophectoderm and apical surface of the uterine epithelium is a common event during the implantation process. In this study, uterine luminal epithelium at implantation and inter-implantation sites was isolated by enzymatic digestion and used for microarray analysis. In a mouse microarray containing 12 345 unigenes, we found 136 genes upregulated more than twofold at the implantation site, while 223 genes were downregulated by at least twofold. Reverse transcription-PCR was used to verify the differential expression of seven upregulated and six downregulated genes chosen randomly from our microarray analysis, and the expression trends were similar. The differential expression patterns of eight upregulated genes were verified by in situ hybridization. Compared with the inter-implantation site on day 5 of pregnancy and the uterus on day 5 of pseudopregnancy, protease, serine, 12 neurotrypsin, endothelin-1, gamma-glutamyl hydrolase, Ras homolog gene family, member U, T-cell immunoglobulin, and mucin domain containing 2, proline-serine-threonine phosphatase-interacting protein 2, 3-monooxgenase/tryptophan 5-monooxgenase activation protein, gamma-polypeptide, and cysteine-rich protein 61 (Cyr61) were upregulated in the luminal epithelium at implantation site on day 5 of pregnancy. These genes may be related to embryo apposition and adhesion during embryo implantation. Cyr61, a gene upregulated at the implantation site, was chosen to examine its expression and regulation during the periimplantation period by in situ hybridization. Cyr61 mRNA was specifically localized in the luminal epithelium surrounding the implanting blastocyst at day 4 midnight and on day 5 of pregnancy, and in the activated uterus, but not expressed in inter-implantation sites and under delayed implantation, suggesting a role for Cyr61 in mediating embryonic-uterine dialog during embryo attachment. Our data could be a valuable source for future study on embryo implantation.

[Regulation of prostaglandin E molecular network in mammalian reproduction].

Prostaglandin E molecular network includes cyclooxygenase, phospholipase A2, prostaglandin E, prostaglandin E receptors, and prostaglandin E synthase. Recently, it was found that PGE2 receptors localized not only on the cell membrane but also on the envelope of nucleus. They are different in the signaling pathways and in regulation mechanism between nuclear receptors and membrane receptors. They compose a delicate network, which plays important roles in mammalian reproduction, especially in most processes of female reproduction.