H2S protects hippocampal neurons against hypoxia-reoxygenation injury by promoting RhoA phosphorylation at Ser188

Inhibition of RhoA-ROCK pathway is involved in the H2S-induced cerebral vasodilatation and H2S-mediated protection on endothelial cells against oxygen-glucose deprivation/reoxygenation injury. However, the inhibitory mechanism of H2S on RhoA-ROCK pathway is still unclear. The aim of this study was to investigate the target and mechanism of H2S in inhibition of RhoA/ROCK. GST-RhoAwild and GST-RhoAS188A proteins were constructed and expressed, and were used for phosphorylation assay in vitro. Recombinant RhoAwild-pEGFP-N1 and RhoAS188A-pEGFP-N1 plasmids were constructed and transfected into primary hippocampal nerve cells (HNCs) to evaluate the neuroprotective mechanism of endothelial H2S by using transwell co-culture system with endothelial cells from cystathionine-γ-lyase knockout (CSE−/−) mice and 3-mercaptopyruvate sulfurtransferase knockout (3-MST−/−) rats, respectively. We found that NaHS, exogenous H2S donor, promoted RhoA phosphorylation at Ser188 in the presence of cGMP-dependent protein kinase 1 (PKG1) in vitro. Besides, both exogenous and endothelial H2S facilitated the RhoA phosphorylation at Ser188 in HNCs, which induced the reduction of RhoA activity and membrane transposition, as well as ROCK2 activity and expression. To further investigate the role of endothelial H2S on RhoA phosphorylation, we detected H2S release from ECs of CSE+/+ and CSE−/− mice, and 3-MST+/+ and 3-MST−/− rats, respectively, and found that H2S produced by ECs in the culture medium is mainly catalyzed by CSE synthase. Moreover, we revealed that both endothelial H2S, mainly catalyzed by CSE, and exogenous H2S protected the HNCs against hypoxia-reoxygenation injury via phosphorylating RhoA at Ser188.

Cerebral Blood Flow in Low Intracranial Pressure Headaches—What Is Known?

Headaches attributed to low cerebrospinal fluid (CSF) pressure are described as orthostatic headaches caused by spontaneous or secondary low CSF pressure or CSF leakages. Regardless of the cause, CFS leaks may lead to intracranial hypotension (IH) and influence cerebral blood flow (CBF). When CSF volume decreases, a compensative increase in intracranial blood volume and cerebral vasodilatation occurs. Sinking of the brain and traction on pain-sensitive structures are thought to be the causes of orthostatic headaches. Although there are many studies concerning CBF during intracranial hypertension, little is known about CBF characteristics during low intracranial pressure. The aim of this review is to examine the relationship between CBF, CSF, and intracranial pressure in headaches assigned to low CSF pressure.

Hypercapnia increases brain viscoelasticity

Brain function, the brain’s metabolic activity, cerebral blood flow (CBF), and intracranial pressure are intimately linked within the tightly autoregulated regime of intracranial physiology in which the role of tissue viscoelasticity remains elusive. We applied multifrequency magnetic resonance elastography (MRE) paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia. Stiffness and viscosity as quantified by the magnitude and phase angle of the complex shear modulus, | G*| and ϕ, as well as CBF of the whole brain and 25 gray matter sub-regions were analyzed prior to, during, and after hypercapnia. In all subjects, whole-brain stiffness and viscosity increased due to hypercapnia by 3.3 ± 1.9% and 2.0 ± 1.1% which was accompanied by a CBF increase of 36 ± 15%. Post-hypercapnia, | G*| and ϕ reduced to normal values while CBF decreased by 13 ± 15% below baseline. Hypercapnia-induced viscosity changes correlated with CBF changes, whereas stiffness changes did not. The MRE-measured viscosity changes correlated with blood viscosity changes predicted by the Fåhræus–Lindqvist model and microvessel diameter changes from the literature. Our results suggest that brain viscoelastic properties are influenced by microvessel blood flow and blood viscosity: vasodilatation and increased blood viscosity due to hypercapnia result in an increase in MRE values related to viscosity.

Selective β1-Antagonism with Bisoprolol Is Associated with Fewer Postoperative Strokes than Atenolol or Metoprolol

Background: Perioperative metoprolol increases postoperative stroke. Animal studies indicate that the mechanism may be related to attenuated β2-adrenoreceptor-mediated cerebral vasodilatation. The authors therefore conducted a cohort to study whether the highly β1-specific β-blocker (bisoprolol) was associated with a reduced risk of postoperative stroke compared with less selective β-blockers (metoprolol or atenolol). Methods: The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac, nonneurologic surgery. The primary outcome was stroke within 7 days of surgery. The secondary outcome was a composite of all-cause mortality, postoperative myocardial injury, and stroke. A propensity score-matched cohort was created to assess the independent association between bisoprolol and less β1-selective agents metoprolol or atenolol. A secondary analysis using logistic regression, based on previously identified confounders, also compared selective β1-antagonism. Results: Twenty-four percent (10,756) of patients were exposed to in-hospital β-blockers. A total of 88 patients (0.2%) suffered a stroke within 7 days of surgery. The matched cohort consisted of 2,462 patients, and the pairs were well matched for all variables. Bisoprolol was associated with fewer postoperative strokes than the less selective agents (odds ratio = 0.20; 95% CI, 0.04–0.91). Multivariable risk-adjustment in the β-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate. Conclusions: The use of metoprolol and atenolol is associated with increased risks of postoperative stroke, compared with bisoprolol. These findings warrant confirmation in a pragmatic randomized trial.