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Essentials von Willebrand Factor (VWF) and ADAMTS13 may affect early injury after subarachnoid hemorrhage (SAH). Early brain injury was assessed in VWF−/−, ADAMTS13−/− and recombinant (r) ADAMTS13 treated mice. VWF−/− and rADAMTS13 treated mice had less brain injury than ADAMTS13−/− and wild-type mice. Early administration of rADAMTS13 may improve outcome after SAH by reducing early brain injury. Summary: Background Early brain injury is an important determinant of poor functional outcome and case fatality after aneurysmal subarachnoid hemorrhage (SAH), and is associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated whether von Willebrand factor (VWF) is involved in the pathogenesis of early brain injury, and whether ultra-early treatment with recombinant ADAMTS-13 (rADAMTS-13) reduces early brain injury after experimental SAH. Methods Experimental SAH in mice was induced by prechiasmatic injection of non-anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control (n = 21), VWF−/− (n = 25), ADAMTS-13−/− (n = 23), and C57BL/6J treated with rADAMTS-13 (n = 26). Mice were killed at 2 h after SAH. Primary outcome measures were microglial activation (IBA-1 surface area) and neuronal injury (number of cleaved caspase-3-positive neurons). Results As compared with controls, microglial activation was decreased in VWF−/− mice (mean difference of − 20.0%, 95% confidence interval [CI] − 4.0% to − 38.6%), increased in ADAMTS-13−/− mice (mean difference of + 34.0%, 95% CI 16.2–51.7%), and decreased in rADAMTS-13-treated mice (mean difference of − 22.1%, 95% CI − 3.4% to − 39.1%). As compared with controls (185 neurons, interquartile range [IQR] 133–353), neuronal injury in the cerebral cortex was decreased in VWF−/− mice (63 neurons, IQR 25–78), not changed in ADAMTS-13−/− mice (53 neurons, IQR 26–221), and reduced in rADAMTS-13-treated mice (45 neurons, IQR 9–115). Conclusions Our findings suggest that VWF is involved in the pathogenesis of early brain injury, and support the further study of rADAMTS-13 as a treatment option for early brain injury after SAH.

The aim of the present study was to identify the site of prostaglandin E2 (PGE2) production in the brain in response to a pyrogenic dose of endotoxin. The presence of PGE2 was detected using immunocytochemistry on Bouin's fixed vibratome sections of control and endotoxin-treated rats. Peripheral administration of endotoxin caused a time-related stimulation of PGE2 immunoreactivity (irPGE2) in the choroid plexus and in the microvasculature of the brain. In addition to these sites, hypophysiotrophic neurons of the paraventricular nucleus (PVN) and supraopticus nucleus (SON) responded with induction of irPGE2 to endotoxin administration. Our data demonstrate that alterations in brain function in response to endotoxin may involve arachidonic metabolities such as PGE2 that are induced at the blood-brain barrier (microvasculature) and blood-liquour barrier (choroid plexus) and in hypohysiotrophic neurons of the rat brain.

The effects of 2-day and 7-day cortisol treatment on immunoreactive corticotropin (ACTH) and beta-endorphin concentrations were measured in the cerebral cortex, hippocampus, hypothalamus, and cerebellum in male rats. Plasma ACTH, beta-endorphin, corticosterone, and cortisol levels were also measured in parallel. Cortisol administration by osmotic minipumps (25 mg/kg/day) maintained a constant, moderately high concentration (23.0 +/- 2.7 micrograms/100 ml) of this glucocorticoid in plasma. Two-day cortisol treatment suppressed the plasma concentration of ACTH and corticosterone, and also decreased, to a lesser degree, concentrations of beta-endorphin. ACTH and beta-endorphin levels in the brain remained unchanged after 2 days of cortisol treatment. After 7-day treatment, however, plasma concentrations of ACTH and beta-endorphin further decreased, while ACTH and beta-endorphin concentrations in the cortex and beta-endorphin concentrations in the cerebellum were also significantly decreased. Peptide concentrations in other brain areas did not change significantly with either 2-day or 7-day cortisol treatment. These data suggest that there are delayed effects of glucocorticoids on pro-opiomelanocortin peptide secretion and/or metabolism in the central nervous system. These findings are consistent with the impaired cognitive functions of patients with diseases, such as Cushing's syndrome and depression, that have long-lasting elevated cortisol secretion.