A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

Ictal and interictal electric source imaging in pre-surgical evaluation: a prospective study.

BACKGROUND AND PURPOSE: Accurate localization of the epileptic focus is essential for surgical treatment of patients with drug-resistant epilepsy. Electric source imaging (ESI) is increasingly used in pre-surgical evaluation. However, most previous studies have analysed interictal (II) discharges. Prospective studies comparing the feasibility and accuracy of II and ictal (IC) ESI are lacking. METHODS: We prospectively analysed long-term video-electroencephalography recordings (LTM) of patients admitted for pre-surgical evaluation. We performed ESI of II and IC signals using two methods, i.e. equivalent current dipole (ECD) and a distributed source model (DSM). LTM recordings employed the standard 25-electrode array (including inferior temporal electrodes). An age-matched template head model was used for source analysis. Results were compared with intracranial recordings, conventional neuroimaging methods [magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)] and outcome at 1 year after surgery. RESULTS: A total of 87 consecutive patients were analysed. ECD gave a significantly higher proportion of patients with localized focal abnormalities (94%) compared with MRI (70%), PET (66%) and SPECT (64%). Agreement between the ESI methods and intracranial recording was moderate to substantial (k = 0.56-0.79). A total of 54 patients were operated (47 patients more than 1 year ago) and 62% of them became seizure-free. The localization accuracy of II-ESI was 51% for DSM and 57% for ECD, and that for IC-ESI was 51% for DSM and 62% for ECD. The differences between the ESI methods were not significant. Differences in localization accuracy between ESI and MRI (55%), PET (33%) and SPECT (40%) were not significant. CONCLUSIONS: The II-ESI and IC-ESI of LTM data have high feasibility and their localization accuracy is similar to that of conventional neuroimaging methods.

In the shadows: Phylogenomics and coalescent species delimitation unveil cryptic diversity in a Cerrado endemic lizard (Squamata: Tropidurus).

The recognition of cryptic diversity within geographically widespread species is gradually becoming a trend in the highly speciose Neotropical biomes. The statistical methods to recognise such cryptic lineages are rapidly advancing, but have rarely been applied to genomic-scale datasets. Herein, we used phylogenomic data to investigate phylogenetic history and cryptic diversity within Tropidurus itambere, a lizard endemic to the Cerrado biodiversity hotspot. We applied a series of phylogenetic methods to reconstruct evolutionary relationships and a coalescent Bayesian species delimitation approach (BPP) to clarify species limits. The BPP results suggest that the widespread nominal taxon comprises a complex of 5 highly supported and geographically structured cryptic species. We highlight and discuss the different topological patterns recovered by concatenated and coalescent species tree methods for these closely related lineages. Finally, we suggest that the existence of cryptic lineages in the Cerrado is much more common than traditionally thought, highlighting the value of using NGS data and coalescent techniques to investigate patterns of species diversity.

Genome-wide data delimits multiple climate-determined species ranges in a widespread Australian fish, the golden perch (Macquaria ambigua).

Species range limits often fluctuate in space and time in response to variation in environmental factors and to gradual niche evolution due to changes in adaptive traits. We used genome-wide data to investigate evolutionary divergence and species range limits in a generalist and highly dispersive fish species that shows an unusually wide distribution across arid and semi-arid regions of Australia. We generated ddRAD data (18,979 filtered SNPs and 1.725million bp of sequences) for samples from 27 localities spanning the native range of golden perch, Macquaria ambigua (Teleostei; Percichthyidae). Our analytical framework uses population genomics to assess connectivity and population structure using model-based and model-free approaches, phylogenetics to clarify evolutionary relationships, and a coalescent-based Bayesian species delimitation method to assess statistical support of inferred species boundaries. Addressing uncertainties regarding range limits and taxonomy is particularly relevant for this iconic Australian species because of the intensive stocking activities undertaken to support its recreational fishery and its predicted range shifts associated with ongoing climate change. Strong population genomic, phylogenetic, and coalescent species delimitation support was obtained for three separately evolving metapopulation lineages, each lineage should be considered a distinct cryptic species of golden perch. Their range limits match the climate-determined boundaries of main river basins, despite the ability of golden perch to cross drainage divides. We also identified cases suggestive of anthropogenic hybridization between lineages due to stocking of this recreationally important fish, as well as a potential hybrid zone with a temporally stable pattern of admixture. Our work informs on the consequences of aridification in the evolution of aquatic organisms, a topic poorly represented in the literature. It also shows that genome-scale data can substantially improve and rectify inferences about taxonomy, hybridization and conservation management previously proposed by detailed genetic studies.

Out of the deep: cryptic speciation in a Neotropical gecko (Squamata, Phyllodactylidae) revealed by species delimitation methods.

Levels of biodiversity in the Neotropics are largely underestimated despite centuries of research interest in this region. This is particularly true for the Cerrado, the largest Neotropical savanna and a formally recognized biodiversity hotspot. Molecular species delimitation methods have become essential tools to uncover cryptic species and can be notably robust when coupled with morphological information. We present the first evaluation of the monophyly and cryptic speciation of a widespread Cerrado endemic lizard, Gymnodactylus amarali, using phylogenetic and species-trees methods, as well as a coalescent-based Bayesian species delimitation method. We tested whether lineages resulting from the analyses of molecular data are morphologically diagnosed by traditional meristic scale characters. We recovered eight deeply divergent molecular clades within G. amarali, and two additional ones from seasonally dry tropical forest enclaves between the Cerrado and the Caatinga biomes. Analysis of morphological data statistically corroborated the molecular delimitation for all groups, in a pioneering example of the use of support vector machines to investigate morphological differences in animals. The eight G. amarali clades appear monophyletic and endemic to the Cerrado. They display several different properties used by biologists to delineate species and are therefore considered here as candidates for formal taxonomic description. We also present a preliminary account of the biogeographic history of these lineages in the Cerrado, evidence for speciation of sister lineages in the Cerrado-Caatinga contact, and highlight the need for further morphological and genetic studies to assess cryptic diversity in this biodiversity hotspot.

[Cortical spreading depolarization phenomena in patients with traumatic and ischemic brain injuries. Results of a pilot study]. / Fenómenos de despolarización cortical propagada en los pacientes con lesiones cerebrales traumáticas e isquémicas. Resultados de un estudio piloto.

OBJECTIVES: To determine the frequency and duration of cortical spreading depolarization (CSD) and CSD-like episodes in patients with traumatic brain injury (TBI) and malignant middle cerebral artery infarction (MMCAI) requiring craniotomy. DESIGN: A descriptive observational study was carried out during 19 months. SETTING: Neurocritical patients. PATIENTS: Sixteen patients were included: 9 with MMCAI and 7 with moderate or severe TBI, requiring surgical treatment. INTERVENTIONS: A 6-electrode subdural electrocorticographic (ECoG) strip was placed onto the perilesional cortex. MAIN VARIABLES OF INTEREST: An analysis was made of the time profile and the number and duration of CSD and CSD-like episodes recorded from the ECoGs. RESULTS: Of the 16 patients enrolled, 9 presented episodes of CSD or CSD-like phenomena, of highly variable frequency and duration. CONCLUSIONS: Episodes of CSD and CSD-like phenomena are frequently detected in the ischemic penumbra and/or traumatic cortical regions of patients with MMCAI who require decompressive craniectomy or of patients with contusional TBI.

Attendance at iron deficiency anaemia clinic: audit of outcomes 5 years on.

AIM: To determine the long-term outcomes of patients in whom no initial cause for their anaemia is established. METHOD: Six hundred and thirty-nine patients presenting to an iron deficiency anaemia pathway were prospectively entered onto a database. Initial assessment included haematological review, coeliac screen, oesophagogastroduodenoscopy and colonic imaging as per British Society of Gastroenterology guidelines. A 5-year audit of outcomes was undertaken using patient medical records and hospital laboratory databases. RESULTS: A diagnosis was found initially in 266 (42%) patients, with 124 (19%) having a gastrointestinal (GI) luminal neoplasm, 54 (8%) of which were malignant. Twelve patients had a nonluminal or non-GI malignancy. Eighty-eight (14%) had benign upper GI bleeding and 23 (4%) had coeliac disease. One hundred and forty-three (22%) did not have confirmed iron deficiency anaemia on review of haematinics. Complete records were available for 595 (93%) patients at 5 years. Of the 373 patients in whom a cause was not initially diagnosed, 6 (2%) were ultimately diagnosed with a GI luminal malignancy and 18 (5%) with a nonluminal or non-GI malignancy. There was no difference in the incidence of malignancies between those with or without confirmed iron deficiency. CONCLUSIONS: Most patients in whom no cause was found at initial investigation resolve on oral iron supplements. Patients with normal ferritin values had as high an incidence of GI malignancies as those with low values and should be investigated. In the over 50s if the anaemia remains after a course of iron further investigation is recommended as there is a significant incidence of both GI and non-GI pathology.

Digest: Dispersal reduction drives rapid diversification in alpine grasshoppers.

Dispersal-associated traits -such as flight ability- influence how species move across the landscape, and can dramatically impact their distributions and patterns of genetic structure. Ortego et al. examine genomic data from two recently diverged alpine grasshopper lineages with distinct wing sizes to assess the demographic impacts of flight loss. The authors showed that flight loss may lead to asymmetric introgression during speciation, and can significantly increase rates of intraspecific diversification.

Pleistocene expansion and connectivity of mesic forests inside the South American Dry Diagonal supported by the phylogeography of a small lizard.

Traditionally focused on Amazonian and Atlantic rainforests, studies on the origins of high Neotropical biodiversity have recently shifted to also investigate biodiversity processes in the South American dry diagonal, encompassing Chaco, Cerrado savannas, and Caatinga seasonally dry tropical forests. The plateau/depression hypothesis states that riparian forests in the Brazilian Shield in central Brazil are inhabited by Pleistocene lineages, with shallow divergences and signatures of population expansion. Moreover, riparian forests may have acted as a vegetation network in the Pleistocene, allowing gene/species flow across the South American dry diagonal. We tested these hypotheses using Colobosaura modesta, a small gymnophthalmid lizard from forested habitats in the Cerrado savannas and montane/submontane forests in the Caatinga. We conducted phylogeographic analyses using a multi-locus dataset, tested alternative demographic scenarios with Approximate Bayesian Computation, and also employed species delimitation tests. We recovered a history of recent colonization and expansion along riparian forests, associated with Pleistocene climate shifts, and the existence of a new species of Colobosaura restricted to the Serra do Cachimbo region. We also present evidence that riparian forests have provided an interconnected network for forest organisms within the South American dry diagonal and that Pleistocene events played an important role in their evolutionary history.

Phylogenomic history of enigmatic pygmy perches: implications for biogeography, taxonomy and conservation.

Pygmy perches (Percichthyidae) are a group of poorly dispersing freshwater fishes that have a puzzling biogeographic disjunction across southern Australia. Current understanding of pygmy perch phylogenetic relationships suggests past east-west migrations across a vast expanse of now arid habitat in central southern Australia, a region lacking contemporary rivers. Pygmy perches also represent a threatened group with confusing taxonomy and potentially cryptic species diversity. Here, we present the first study of the evolutionary history of pygmy perches based on genome-wide information. Data from 13 991 ddRAD loci and a concatenated sequence of 1 075 734 bp were generated for all currently described and potentially cryptic species. Phylogenetic relationships, biogeographic history and cryptic diversification were inferred using a framework that combines phylogenomics, species delimitation and estimation of divergence times. The genome-wide phylogeny clarified the biogeographic history of pygmy perches, demonstrating multiple east-west events of divergence within the group across the Australian continent. These results also resolved discordance between nuclear and mitochondrial data from a previous study. In addition, we propose three cryptic species within a southwestern species complex. The finding of potentially new species demonstrates that pygmy perches may be even more susceptible to ecological and demographic threats than previously thought. Our results have substantial implications for improving conservation legislation of pygmy perch lineages, especially in southwestern Western Australia.

Laser-Doppler evaluation of rat brain microcirculation: comparison with the [14C]-iodoantipyrine method suggests discordance during cerebral blood flow increases.

Laser-Doppler flowmetry (LDF) is very popular for measurements of dynamic changes of cerebral blood flow (CBF). We studied whether changes of CBF measured by LDF correlate with CBF measured by the [14C]iodoantipyrine (IAP) technique in the range relevant for most physiological experiments (-30-(+)130%). LDF was recorded biparietally by two laser-Doppler probes in halothane-anesthetized rats. Absolute CBF was measured in tissue samples of both parietal cortices after [14C]iodoantipyrine was given i.v. CBF of one hemisphere was reduced by an episode of cortical spreading depression (CSD), which markedly reduces the responsiveness of the ipsilateral cortical CBF to vasoactive stimuli for up to 30 min, while CBF regulation of the contralateral cortex remains intact. CBF was measured under normoventilated, hypercapnic, and hypoxic conditions. The relative changes of CBF measured by the LDF technique were independent of the preceding baseline LDF value. Absolute CBFIAP values correlated poorly to the simultaneously recorded arbitrary LDF values (r = 0.44). In contrast, the ratio of CBFIAP values correlated with the ratio of the relative LDF changes between the two hemispheres (p < 0.001). At reduced CBF, no significant difference was found between methods. At increased CBF, however, LDF was greater than CBFIAP, as indicated by a slope of correlation of 1.45 (p < 0.005).

Laminar analysis of cerebral blood flow in cortex of rats by laser-Doppler flowmetry: a pilot study.

Laser-Doppler flowmetry (LDF) is a reliable method for estimation of relative changes of CBF. The measurement depth depends on wavelength of the laser light and the separation distance of transmitting and recording optical fibers. We designed an LDF probe using two wavelengths of laser light (543 nm and 780 nm), and three separation distances of optical fibers to measure CBF in four layers of the cerebral cortex at the same time. In vitro comparison with electromagnetic flow measurements showed linear relationship between LDF and blood flow velocity at four depths within the range relevant to physiologic measurements. Using artificial brain tissue slices we showed that the signal for each channel decreased in a theoretically predictable fashion as a function of slice thickness. Application of adenosine at various depths in neocortex of halothane-anesthetized rats showed a predominant CBF increase at the level of application. Electrical stimulation at the surface of the cerebellar cortex demonstrated superficial predominance of increased CBF as predicted from the distribution of neuronal activity. In the cerebellum, hypercapnia increased CBF in a heterogeneous fashion, the major increase being at apparent depths of approximately 300 and 600 microns, whereas in the cerebral cortex, hypercapnia induced a uniform increase. In contrast, the CBF response to cortical spreading depression in the cerebral cortex was markedly heterogeneous. Thus, real-time laminar analysis of CBF with spatial resolution of 200 to 300 microns may be achieved by LDF. The real-time in depth resolution may give insight into the functional organization of the cortical microcirculation and adaptive features of CBF regulation in response to physiologic and pathophysiologic stimuli.

Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex.

Laser-Doppler perfusion imaging (LDPI) is a new technique which provides recordings of blood flow in rapid sequence. In this study we applied LDPI to the brain for the first time to demonstrate propagating waves of cortical spreading depression (CSD) elicited by a needle stab in the frontal cortex of barbiturate-anesthetized rats. Under resting conditions, LDPI recordings of the superficial cortex showed a heterogeneous pattern, partly due to the high flow rate in pial arteries compared with cortical tissue. Within 1 min after elicitation of the CSD a zone of increased signal intensity (96 +/- 5%) up to 6 mm across appeared in the exposed cortex. The rate of propagation away from the site of elicitation for 16 such waves was 2.8 +/- 0.1 mm min-1. The increased signal intensity was partly due to dilatation of pial arterioles and veins, partly to increased blood flow in the microvascular bed. The data are consistent with previous studies of CSD using other techniques for measurement of cortical blood flow. LDPI gives real time images of cerebral blood flow, and may be applied to demonstrate CSD or CSD-like phenomena during neurosurgical operations in man.

Transient hyperemia succeeds oligemia in the wake of cortical spreading depression.

Regional cerebral blood flow (rCBF) was examined following single episodes of cortical spreading depression (CSD) in rat brain after an intravenous bolus injection of [14C]iodoantipyrine. Cortical rCBF decreased to approximately 75% of control values during the first 60 min after CSD. This change was succeeded at 90-105 min by a small, transient flow increase. rCBF returned to normal at 120 min after CSD, and remained normal for the following 2 h. The same sequence of rCBF changes has been recorded in patients during migraine attacks. This study therefore supports the notion that CSD may serve as an animal model of migraine.

Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex.

We have examined the effect of cortical spreading depression (SD) and anoxic depolarization (AD) on the interstitial concentration changes of amino acids (AA) in the neocortex of anesthetized rats using microdialysis and HPLC. Accompanying SD alanine increased to 126 +/- 11%, arginine to 116 +/- 3%, aspartate to 160 +/- 17%, glutamate to 163 +/- 9%, glycine to 158 +/- 21%, serine to 125 +/- 9%, and taurine to 172 +/- 15% (mean +/- 1 S.E.M.). The increases lasted for about 1 min. Histidine decreased to 74% +/- 4% at 1 min following SD, and returned to normal 4 min later. Cardiac arrest triggered AD after approximately 2 min, immediately followed by changes of interstitial AAs. At 5 min after AD alanine had increased to 183 +/- 13%, aspartate to 3,458 +/- 656%, GABA to 338 +/- 35%, glutamate to 1,696 +/- 546%, glycine to 297 +/- 37%, serine to 153 +/- 12%, and taurine to 1721 +/- 98% as compared to control values (mean +/- 1 S.E.M.). Histidine decreased to 78 +/- 2% at 3 min following AD while arginine exhibited insignificant variations around the baseline. The increase of glutamate during SD is consistent with activation of NMDA-receptors as an essential requirement for this reaction. The increase of AAs may also contribute to the sequence of events leading to AD, though the exact mechanism remains unknown. SD is an important pathophysiological mechanism of the ischemic penumbra associated with focal cerebral ischemia, while AD reflects the electrophysiological status of the infarct core.(ABSTRACT TRUNCATED AT 250 WORDS)

Measure of expression of mitochondrial related genes in human mononuclear blood cells, adipose white tissue and smooth muscle cells.

BACKGROUND: The role of mitochondrial dysfunction is currently studied intensively, but the cumbersome procedure of obtaining tissue from humans has restricted the number of subjects studied. Therefore, the aim of the present study was to examine the expression of mitochondrial related genes in blood cells from humans and to compare the results with measurements of mitochondrial membrane potential known to be regulated by thyroid hormones. METHODS: In a group of 17 healthy women subscribed for hysterectomy on a benign basis, muscle tissue, fat tissue samples and blood specimens were obtained. Mitochondrial mass and membrane potential was examined in peripheral blood monocytes by flow cytometry. Gene expression of PGC-1alpha, PGC-1beta, NFR-1, NRF-2 and TFAM was determined by real-time PCR. RESULTS: All genes were expressed in the 3 tissues examined, though with different magnitude. Most genes were expressed in mononuclear blood cells at a magnitude comparable to that in white adipose tissue. Furthermore, a significant correlation was observed between PGC-1beta and Mitochondrial Membrane Potential (MMP) and Mitochondrial Mass (MM). CONCLUSION: Measurement of expression of mitochondrial related genes in human mononuclear blood cells may be useful for examining mitochondrial function and regulation by thyroid hormones in humans.

Application of stereological estimates in patients with severe head injuries using CT and MR scanning images.

Severe brain damage is often followed by serious complications. Quantitative measurements, such as regional volume and surface area under various conditions, are essential for understanding functional changes in the brain and assessing prognosis. The affected brain tissue is variable, hence traditional imaging methods are not always applicable and automatic methods may not be able to match the individual observer. Stereological techniques are alternative tools in the quantitative description of biological structures, and have been increasingly applied to the human brain. In the present study, we applied stereological techniques to representative CT and MRI brain scans from five patients to describe how stereological methods, when applied to scans of trauma patients, can provide a useful supplement to the estimation of structural brain changes in head injuries. The reliability of the estimates was tested by obtaining repeated intra- and interobserver estimates of selected subdivisions of the brain in patients with acute head injury, as well as in an MR phantom. The estimates of different subdivisions showed a coefficient of variation (CV) below 12% in the patients and below 7% for phantom estimation. The validity of phantom estimates was tested by the average deviation from the true geometric values, and was below 10%. The stereological methods were compared with more traditional region-based methods performed on medical imaging, which showed a CV below 7% and bias below 14%. It is concluded that the stereological estimates may be useful tools in head injury quantification.

Examination of the role of nitric oxide for the hypercapnic rise of cerebral blood flow in rats.

We examined the effect of nitric oxide synthase (NOS) inhibition and tetrodotoxin (TTX) on the increase of cerebral blood flow (CBF) in parietal (CoBF) and cerebellar cortex (CeBF) in response to hypercapnia. Rats were anesthetized with halothane and artificially ventilated. Hypercapnia was induced by adding 5% CO2 to the inhalation mixture. CoBF and CeBF were measured by laser-Doppler flowmetry. NOS inhibition was achieved by intravenous (30 mg/kg) and/or topical application (1 mM) of NG-nitro-L-arginine (L-NNA). Activity in perivascular nerves around pial and cortical vessels was inhibited by topical application of TTX (20 microM). Under control conditions, hypercapnia (66 +/- 1 mmHg) increased CoBF by 70 +/- 4% and CeBF by 96 +/- 5%. Systemic L-NNA decreased the baseline level of CoBF and CeBF by 11 +/- 3%, but topical L-NNA did not affect baseline flow. Intravenous L-NNA attenuated the hypercapnic increase of CoBF by 77 +/- 5% and CeBF by 63 +/- 4% within 10-20 min. Topical L-NNA attenuated the hypercapnic increase of CoBF by 52 +/- 6% and CeBF by 29 +/- 5% after 45-min exposure. Both CoBF and CeBF decreased rapidly when L-NNA was infused during sustained hypercapnia, but not when L-NNA was applied topically. Effect of intravenous L-NNA was partially prevented by pretreatment with intravenous L-arginine. Intravenous or topical L-NNA enhanced the rise of CBF elicited by cortical spreading depression, adenosine (1 mM), or sodium nitroprusside (300 microM), except in the cerebellum where topical L-NNA attenuated the rise of CBF elicited by adenosine by 53%.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression.

Nerve cells release nitric oxide (NO) in response to activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We explored the hypothesis that NO influences the changes of cerebral blood flow (CBF) during cortical spreading depression (CSD), which is known to be associated with NMDA receptor activation. CBF was monitored in parietal cortex by laser-Doppler flowmetry in halothane-anesthetized rats. Under control conditions, CSD induced regular changes of CBF, which consisted of four phases: a brief hypoperfusion before the direct current (DC) shift; a marked CBF rise during the DC shift; followed by a smaller, but protracted increase of CBF; and a prolonged CBF reduction (the oligemia). NO synthase inhibition by intravenous and/or topical application of NG-nitro-L-arginine enhanced the brief initial hypoperfusion, but the CBF increases and the oligemia were unchanged. L-Arginine prevented the development of the prolonged oligemia after CSD but had no influence on the marked rise of CBF during CSD. Animals treated with L-arginine recovered the reduced vascular reactivity to hypercapnia after CSD much faster than control rats. Functional denervation of cortical and pial arterioles by tetrodotoxin accentuated the pre-CSD hypoperfusion and the oligemia but did not affect the CBF increases. The results suggest that NO is important for the changes of cerebrovascular regulation following CSD. The observations may have clinical importance, since CBF changes during migraine may be triggered by CSD.