Arguments against the role of cortical spreading depression in migraine.

Cortical spreading depression (CSD) is a wave of increased electrocortical activity and vasodilation, followed by sustained decreased activity and prolonged vasoconstriction. Although the discovery of CSD has been ascribed to Leão, rather than vasoconstriction, he only observed a depression of neural activity combined with vasodilation, with much weaker stimulation than used by his followers. There is a longstanding belief that CSD underlies migraine aura, with its positive symptoms such as mosaic patterns and its negative symptoms such as scotoma, and a similar propagation speed and vasoreaction pattern.

Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid.

The blood-brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism.

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.

Vitamin B-6 vitamers in human plasma and cerebrospinal fluid.

Background: Vitamin B-6 comprises a group of 6 interrelated vitamers and is essential for numerous physiologic processes, including brain functioning. Genetic disorders disrupting vitamin B-6 metabolism have severe clinical consequences.

Objective: To adequately diagnose known and novel disorders in vitamin B-6 metabolism, a reference set is required containing information on all vitamin B-6 vitamers in plasma and cerebrospinal fluid (CSF).

Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.

Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR.

D-amino acid aberrations in cerebrospinal fluid and plasma of smokers.

The glutamatergic neurotransmission system and the N-methyl-D-aspartate receptor (NMDAR) have been implicated in smoking and alcohol consumption behavior. Preclinical studies have demonstrated that nicotine and ethanol influence NMDAR functionality, which may have a role in tendencies to consume these substances. Nonetheless, little is known about concentrations of NMDAR coagonists in the cerebrospinal fluid (CSF) and plasma of individuals who smoke or consume alcohol.

Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population.

Quality of intraoperatively salvaged unwashed blood in hip arthroplasty.

Background And Objectives: Transfusion of autologous whole blood is one available method to reduce the need for allogenic blood transfusion. The aim of the present study was to investigate the quality of shed blood collected in a new intraoperative autotransfusion system.

Materials And Methods: In this prospective study fifteen consecutive patients who were scheduled for elective total hip arthroplasty were included.

Migraine: possible role of shear-induced platelet aggregation with serotonin release.

Background: Migraine patients are at an increased risk for stroke, as well as other thromboembolic events. This warrants further study of the role of platelets in a proportion of migraine patients.

Objective: To extend the "platelet hypothesis" using literature data and observations made in a rat model of shear stress-induced platelet aggregation.

A common variant in ERBB4 regulates GABA concentrations in human cerebrospinal fluid.

The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy ((1)H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant impact of this genetic variant on expression of ERBB4 in the hippocampus and dorsolateral prefrontal cortex in human post mortem tissue.

Season of sampling and season of birth influence serotonin metabolite levels in human cerebrospinal fluid.

Background: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults.

Methodology/principal Findings: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures.

COX-2 Inhibition by Use of Rofecoxib or High Dose Aspirin Enhances ADP-Induced Platelet Aggregation in Fresh Blood.

Aim: Increased cardiovascular risk after use of selective or nonselective cyclooxygenase-2 (COX-2)-inhibitors might partly be caused by enhanced platelet aggregability. However, an effect of COX-2 inhibition on platelets has so far not been observed in humans.

Methods: We tested in healthy volunteers the effect of COX-2-inhibition nearly in-vivo, i.

Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?

Background: The sum of undesirable side effects, occurring during haemodialysis (HD), is called bio-incompatibility. Concerning platelets, both an increase in the expression of the cell surface marker P-selectin (CD62p) and release of the intracellular granule product platelet factor 4 (PF4) have been described. However, as PF4 is also abundantly present on endothelium-bound proteoglycans, it is questionable whether the HD-induced increase is exclusively attributable to release from platelets.

Reduction in platelet activation by citrate anticoagulation does not prevent intradialytic hemodynamic instability.

Background: The etiology of intradialytic hemodynamic instability is multifactorial. Of the various factors involved, a rise in core temperature seems to be crucial. In this respect, the bioincompatibility of hemodialysis (HD) treatment might play an important role.

Cyclooxygenase-2 inhibitors enhance shear stress-induced platelet aggregation.

Objectives: We aimed to investigate the effect of parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on in vivo shear stress-induced platelet aggregation in a rat model of arterial bypass with focal narrowing.

Background: Long-term use of COX-2 inhibitors is associated with increased incidence of adverse cardiovascular events, especially in patients with a history of cardiovascular disease. These patients are at risk for thrombotic occlusion of arterial stenoses initiated by shear stress-induced platelet aggregation.

Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and prevention with clopidogrel.

Objectives: Use of extracorporeal circuits in cardiopulmonary bypass and hemodialysis often causes bleeding problems and hypotension. As shown previously, this might be caused by activation of blood platelets due to pumping. The present study investigates the mechanism of pump-induced platelet aggregation and its possible prevention.

Large-dose intrathecal sufentanil prevents the hormonal stress response during major abdominal surgery: a comparison with intravenous sufentanil in a prospective randomized trial.

We studied the effect of large-dose intrathecal sufentanil (ITS) for major abdominal surgery on the hormonal stress response. Forty patients were randomly allocated to receive either IV sufentanil (IVS) or 150 microg of ITS as part of general anesthesia. In the IVS group, adrenocorticotropic hormone (ACTH) and cortisol concentrations were larger than baseline and the ITS group, 60 min after incision and at skin closure.

The baroreflex is counteracted by autoregulation, thereby preventing circulatory instability.

The aims of this study were (a) to apply in the animal with intact baroreflex a two-point method for estimation of overall, effective open-loop gain, G0e, which results from the combined action of baroregulation and total systemic autoregulation on peripheral resistance; (b) to predict specific baroreflex gain by correcting the effective gain for the autoregulation gain; and (c) to discuss why the effective gain is usually as low as 1-2 units. G0e was estimated from two measurements of both cardiac output, Q, and mean systemic arterial pressure, P: one in the reference state (set-point) and the other in a steady-state reached 1-3 min after a small cardiac output perturbation. In anaesthetized cats and dogs a cardiac output perturbation was accomplished by partial occlusion of the inferior vena cava and by cardiac pacing, respectively.

Haemodialysis-induced pulmonary granulocyte sequestration in rabbits is organ specific.

Background: Haemodialysis (HD) with cuprophan (CU) dialysers leads to a severe transient granulocytopenia. In the present study, we challenge the hypothesis that granulocytes sequester within the pulmonary vasculature simply because this is the first vascular bed encountered. This hypothesis is based upon experiments in which activated plasma or complement fragments were infused into animals, and may not pertain to the more complex HD situation.

Hypotension caused by extracorporeal circulation: serotonin from pump-activated platelets triggers nitric oxide release.

Background: Cardiopulmonary bypass and hemodialysis often cause hypotension. We investigated a possible role of pump-induced platelet activation with consequent serotonin release.

Methods And Results: In rats, a heparin-coated extracorporeal shunt was placed between the proximal part of a carotid artery and the distal part of a femoral artery.

Extracorporeal circulation can induce hypotension by both blood-material contact and pump-induced platelet aggregation.

Objective: Use of extracorporeal systems in cardiopulmonary bypass and dialysis induces vascular reactions, which can lead to hypotension and lung edema.

Methods: To study the contribution of blood-material contact and use of a roller pump, as well as prevention of their adverse effects, we perfused a rat hind leg with a tube connecting a carotid and a femoral artery.

Results: Autoperfusion of an uncoated tube caused a fall of aortic pressure and femoral resistance to 66% +/- 16% and 76% +/- 15%, respectively, of their initial values within 2 hours, whereas in control animals without a shunt, these variables hardly changed (to 94% +/- 2.

In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions.

Background: The aim of this study was to develop a model for hemodialysis (HD) in small animals using conventional dialysis equipment that would allow the intravital microscopic observation of leukocyte-endothelial interactions in vivo.

Methods: Cuprophan dialyzers were adapted to obtain a similar ratio of membrane area to blood volume as in clinical HD. A silicone ring was inserted into the dialyzer's inlet to limit the number of blood-perfused capillaries.