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Byline: Uddalak. Chakraborty, Subhadeep. Gupta, Arpan. Dutta, Biman. Ray, Ashok. Gandhi, Trilochan. Srivastava, Rahul. Kumar, Deep. Das Background and Aims: Intracranial arterial dissections commonly involve the vertebrobasilar system leading to [...]

Byline: Hiroki. Uchikawa, Kazumi. Nitta, Yukihiro. Imaoka, Akira. Tempaku, Hironori. Arima, Akitake. Mukasa, Hajime. Kamada Background: Endovascular treatment is the preferred treatment for acute ischemic stroke (AIS) due to main [...]

Exercise preconditioning has been shown to be effective in improving behavioral and neuropathological indices after cerebral ischemia. We evaluated the effect of exercise preconditioning, 17[beta]-estradiol, and their combination on stroke outcome using an experimental model of stroke in ovariectomized (OVX) mice. OVX mice were randomly assigned to 4 groups as follows: control (stroke), exercise (exercise and stroke), estradiol (17[beta]-estradiol and stroke), and exercise+estradiol (exercise and 17[beta]estradiol and stroke). Exercise preconditioning was performed on a treadmill 5 days/week, 40 min/day, at a speed of 18 m/min for 4 weeks. 17[beta]-estradiol was gavaged (40 [micro]g/kg per day) for 4 weeks. Stroke was induced by permanent middle cerebral artery occlusion (pMCAO), and neurological deficits were evaluated 1, 2, and 7 days after stroke. Then, the serum concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10) and infarct volumes were assessed. Exercise preconditioning and 17[beta]-estradiol induced a better outcome compared with the control ischemic mice, which was manifested by decrease in MMP-9, increase in IL-10, diminished infarct volume, and improved neurological deficits. Concomitant administration of 17[beta]-estradiol and exercise also significantly improved these parameters. Exercise preconditioning or administration of 17[beta]-estradiol alone or in combination before pMCAO induced significant neuroprotection in OVX mice. Key words: exercise preconditioning, estradiol, stroke, permanent middle cerebral artery occlusion, interleukin 10, matrix metalloproteinase-9. On a montre que le preconditionnement par l'exercice physique est efficace en vue d'ameliorer les indices comportementaux et neuropathologiques apres une ischemie cerebrale. Nous avons evalue les effets du preconditionnement par l'exercice, du 17[beta]-estradiol et de leur association sur les resultats de l'accident vasculaire cerebral (AVC) a l'aide d'un modele experimental d'AVC chez la souris ovariectomisee (OVX). Nous avons reparti aleatoirement des souris OVX dans les quatre groupes suivants : temoin (AVC), exercice (exercice et AVC), estradiol (17[beta]-estradiol et AVC) et exercice+estradiol (exercice avec 17[beta]-estradiol et AVC). Les souris se pretaient au preconditionnement par l'exercice sur tapis roulant, 5 jours/semaine, 40 min/jour, a une vitesse de 18 m/min, sur 4 semaines. Nous avons administre le 17[beta]- estradiol par gavage (40 [micro]g/kg par jour) sur 4 semaines. Nous avons provoque l'AVC par l'occlusion permanente de l'artere cerebrale moyenne (OpACM) et evalue les deficits neurologiques 1, 2 et 7 jours apres l'AVC. Puis, nous avons evalue les concentrations seriques de metalloproteinase matricielle 9 (MMP-9) et d'interleukine 10 (IL-10), ainsi que le volume de l'infarctus. Le preconditionnement par l'exercice et le 17[beta]-estradiol permettaient d'obtenir de meilleurs resultats que chez les souris temoins avec ischemie, ce qui se manifestait par une diminution des taux de MMP-9, une augmentation des taux d'IL-10, ainsi qu'une diminution du volume de l'infarctus, avec une amelioration sur le plan des deficits neurologiques. L'administration concomitante de 17[beta]-estradiol et d'exercice permettait aussi d'obtenir des ameliorations notables sur le plan de ces parametres. Le preconditionnement par l'exercice ou l'administration de 17[beta]-estradiol, seuls ou en association, avant l'OpACM entrainaient une neuroprotection marquee chez les souris OVX. [Traduit par la Redaction] Mots-cles : preconditionnement par l'exercice physique, estradiol, AVC, occlusion permanente de l'artere cerebrale moyenne, interleukine 10, metalloproteinase matricielle 9., Introduction Stroke is one of the most common causes of death and permanent disability in adults, with a worldwide prevalence of about 0.25% (Mozaffarian et al. 2015). Transient or permanent [...]

Byline: Atman. Das, Rajesh. Meena, Ramesh. Doddamani, Shashwat. Mishra, Deepak. Agrawal Sir, A 40-year-old male patient, previously operated for left anterior 1/3 parasagittal atypical meningioma in 2008 [Figure 1]a, presented [...]

The structural and functional integrity of the brain, and therefore, cognition, are critically dependent on the appropriate control of blood flow within the cerebral circulation. Inadequate flow leads to ischemia, whereas excessive flow causes small vessel rupture and (or) blood-brain-barrier disruption. Cerebral blood flow is controlled through the interplay of several physiological mechanisms that regulate the contractile state of vascular smooth muscle cells (VSMCs) within the walls of cerebral resistance arteries and arterioles. The myogenic response of cerebral VSMCs is a key mechanism that is responsible for maintaining constant blood flow during variations in systemic pressure, i.e., flow autoregulation. Inappropriate myogenic control of cerebral blood flow is associated with, and prognostic of, neurological deterioration and poor outcome in patients with several conditions, including type 2 diabetes. Here, we review recent advances in our understanding of the role of inappropriate Rho-associated kinase activity as a cause of impaired myogenic regulation of cerebral arterial diameter in type 2 diabetes. Key words: cerebral autoregulation, vascular smooth muscle, [Ca.sup.2+] sensitization, myosin light chain phosphatase, actin cytoskeleton. L'integrite structurale et fonctionnelle du cerveau, et consequemment, la cognition, sont significativement dependantes du controle adequat du flux sanguin dans la circulation cerebrale. Un flux insuffisant conduit a l'ischemie, alors qu'un flux excessif provoque la rupture des petits vaisseaux et (ou) de la barriere sang-cerveau. Le flux sanguin cerebral est controle par l'interaction de plusieurs mecanismes physiologiques qui regulent l'etat contractile des cellules vasculaires musculaires lisses (CVML) a l'interieur des parois des arteres et des arterioles de resistance cerebrales. La reponse myogenique des CVML cerebrales constitue un mecanisme central qui est responsable de maintenir constant le flux sanguin lors de variations de la pression systemique, i.e., l'autoregulation du flux. Un controle myogenique du flux sanguin cerebral inadequat est associe et constitue un facteur pronostic de la deterioration neurologique et du resultat defavorable chez les patients a affections multiples, incluant le diabete de type 2. Les auteurs passent ici en revue les progres recents de notre comprehension du role d'une activite aberrante de ROCK (<>) comme cause de la regulation myogenique reduite du diametre arteriel cerebral dans le diabete de type 2. [Traduit par la Redaction] Mots-cles : autoregulation cerebrale, muscle lisse vasculaire, sensibilisation au [Ca.sup.2+], phosphatase de la chaine legere de la myosine, cytosquelette d'actine., Introduction This tribute issue of CJPP celebrates the fundamental contribution of Professor Newman L. Stephens to our understanding of airway smooth muscle contractility in health and airway hyperresponsiveness in asthma. [...]

This study evaluated endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in isolated middle cerebral arteries (MCA) from Dahl salt-sensitive (Dahl SS) rats and three different congenic strains that contain a portion of Brown Norway (BN) chromosome 13 introgressed onto the Dahl SS genetic background through marker-assisted breeding. Two of the congenic strains carry a 3.5-Mbp portion and a 2.6-Mbp portion of chromosome 13 that lie on opposite sides of the renin locus, while the third contains a 2.0-Mbp overlapping region that includes the BN renin allele. While maintained on a normal salt (0.4% NaCl) diet, MCAs from Dahl SS rats and the congenic strains retaining the Dahl SS renin allele failed to dilate in response to ACh, whereas MCAs from the congenic strain carrying the BN renin allele exhibited normal vascular relaxation. In congenic rats receiving the BN renin allele, vasodilator responses to ACh were eliminated by nitric oxide synthase inhibition with [N.sup.G]-nitro-L-arginine methyl ester, angiotensin-converting enzyme inhibition with captopril, and [AT.sub.1] receptor blockade with losartan. [N.sup.G]-nitro-L-arginine methyl ester-sensitive vasodilation in response to ACh was restored in MCAs of Dahl SS rats that received either a 3-day infusion of a subpressor dose of angiotensin II (3 ng x [kg.sup.-1] x [min.sup.-1] iv), or chronic treatment with the superoxide dismutase mimetic tempol (15 mg x [kg.sup.-1] x [day.sup.-1]). These findings indicate that the presence of the Dahl SS renin allele plays a crucial role in endothelial dysfunction present in the cerebral circulation of the Dahl SS rat, even in the absence of elevated dietary salt intake, and that introgression of the BN renin allele rescues endothelium-dependent vasodilator responses by restoring normal activation of the renin-angiotensin system. renin-angiotensin system; vascular dysfunction; physiological genomics; vasodilation; angiotensin II; oxidant stress doi: 10.1152/ajpheart.00700.2010.

The melastatin transient receptor potential (TRP) channel TRPM4 is a critical regulator of vascular smooth muscle cell membrane potential and contractility. Activation of the channel is [Ca.sup.2+]-dependent, but prolonged exposure to high (> 1 [micro]M) levels of intracellular [Ca.sup.2+] causes rapid (within -2 min) desensitization of TRPM4 currents under conventional whole cell and inside-out patch-clamp conditions. The goal of the present study was to establish a novel method to record sustained TRPM4 currents in smooth muscle cells under near-physiological conditions. Using the amphotericin B-perforated patch-clamp technique, we recorded and characterized sustained (up to 30 min) transient inward cation currents (TICCs) in freshly isolated cerebral artery myocytes. In symmetrical cation solutions, TICCs reversed at 0 mV and had an apparent unitary conductance of 25 pS. Replacement of extracellular [Na.sup.+] with the nonpermeable cation N-methyl-D-glucamine abolished the current. TICC activity was attenuated by the TRPM4 blockers fluflenamic acid and 9-phenanthrol. Selective silencing of TRPM4 expression using small interfering RNA diminished TICC activity, suggesting that the molecular identity of the responsible ion channel is TRPM4. We used the perforated patch-clamp method to test the hypothesis that TRPM4 is activated by intracellular [Ca.sup.2+] signaling events. We found that TICC activity is independent of [Ca.sup.2+] influx and ryanodine receptor activity but is attenuated by sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase inhibition and blockade of inositol 1,4,5-trisphosphate receptor-mediated [Ca.sup.2+] release from the sarcoplasmic reticulum. Our findings suggest that TRPM4 channels in cerebral artery myocytes are regulated by [Ca.sup.2+] release from inositol 1,4,5-trisphosphate receptor on the sarcoplasmic reticulum. amphotericin B; cation channels; inositol 1,4,5-trisphosphate; small interfering RNA; transient receptor potential channels doi: 10.1152/ajpcell.00550.2009.

Ryanodine receptors (RyRs) regulate contractility in resistance-size cerebral artery smooth muscle, yet their molecular identity, subcellular location, and phenotype in this tissue remain unknown. Following rat resistance-size cerebral artery myocyte sarcoplasmic reticulum (SR) purification and incorporation into POPE-POPS-POPC (5:3:2; wt/wt) bilayers, unitary conductances of 110 [+ or -] 8, 334 [+ or -] 15, and 441 [+ or -] 27 pS in symmetric 300 mM [Cs.sup.+] were usually detected. The most frequent (34/40 bilayers) conductance (334 pS) decreased to [less than or equal to] 100 pS when [Cs.sup.+] was replaced with [Ca.sup.2+]. The predominant conductance displayed 66 bursts/min with at least three open and three closed states. The steady-state activity ([NP.sub.o])-voltage curve was bell shaped, with [NP.sub.o] drastically decreasing when voltage was switched from -30 to -40 mV. [NP.sub.o] increased when intracellular calcium ([Ca.sup.2+.sub.i]) was raised within 0.1-100 [micro]M to abruptly diminish with higher [Ca.sup.2+.sub.i]. Thus maximal activity occurred within the [Ca.sup.2+.sub.i] range found in rat cerebral artery myocytes under physiological conditions. [NP.sub.o] was reduced by ruthenium red (80 [micro]M), increased monotonically by caffeine (0.1-5 mM) or ryanodine (0.05-5 [micro]M), and unaffected by heparin (2 mg/ml). This phenotype resembles that of cardiac RyR and recombinant RyR2. RT-PCR detected RyR1, RyR2, and RyR3 transcripts in cerebral artery myocytes. However, real-time PCR indicated that RyR2 was 4 and 1.5 times more abundant than RyRI and RyR3, respectively. Consistently, Western blotting showed that the RyR2 product was very abundant. Immunofluorescence showed that each RyR isoform distributed differentially among subcellular compartments. In particular, RyR2 was drastically stronger in the subplasmalemma than in other compartments, underscoring the predominance of RyR2 in a compartment where SR is abundant. Consistently, RyR from SR-enriched membranes displayed pharmacological specificity typical of RyR2, being activated by digoxin (1 [micro]M), resistant to dantrolene (100 [micro]M), and shifted to a subconductance by neomycin (100 nM). Therefore, RyR2 is the predominant molecular and functional RyR that is expressed in the SR membrane of rat resistance-size cerebral artery myocytes. calcium-release channels: vascular smooth muscle doi: 10.1152/ajpcell.00318.2009.

Store-operated channels (SOC) and store-operated [Ca.sup.2+] entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type [Ca.sup.2+] ([Ca.sup.2+.sub.L]) channels are thought to be fully responsible for agonist-induced [Ca.sup.2+] influx and vasoconstriction. We present evidence that SOC and their activation via a [Ca.sup.2+] -independent phospholipase [A.sub.2] ([iPLA.sub.2])-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular [Ca.sup.2+] in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) [Ca.sup.2+] and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a [Ca.sup.2.sub.L+] inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and [Ca.sup.2.sub.L+] channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of [iPLA.sub.2][beta] totally inhibited PE-induced [Ca.sup.2+] influx and constriction in cerebral, mesenteric, and carotid arteries, whereas [K.sup.+]-induced [Ca.sup.2+] influx and vasoconstriction mediated by [Ca.sup.2+.sub.L] channels were not affected. Thus [iPLA.sub.2]-dependent activation of SOC is crucial for agonist-induced [Ca.sup.2+] influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of [Ca.sup.2+] stores, nonselective SOC are activated via an [iPLA.sub.2]-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of [Ca.sup.2+.sub.L] channels and lead to [Ca.sup.2+] entry and vasoconstriction. store-operated calcium entry; smooth muscle cells; constriction

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1552-6569.2006.00061.x Byline: Steven J. Shook (1), Rishi Gupta (1), Nirav A. Vora (1), Andrew L. Tievsky (1), Irene Katzan (1), Derk W. Krieger (1) Keywords: Brain ischemia; cerebrovascular accident; diffusion magnetic resonance imaging; hydroxymethylglutaryl (HMG)-CoA reductase inhibitors; retrospective studies; risk factors; treatment outcome Abstract: ABSTRACT Background. Studies have shown an association between HMG-CoA reductase inhibitors (statins) and improved stroke outcomes, possibly secondary to neuroprotective properties. Objective. To assess whether patients taking statins prior to ischemic stroke have smaller infarcts on magnetic resonance imaging (MRI), adjusting for other relevant clinical factors. Design. We retrospectively reviewed the Cleveland Clinic Foundation (CCF) Neurology Inpatient Database from June 2002 through June 2004. Demographics, medications, stroke subtype, diffusion-weighted imaging (DWI) infarct volume, admission NIHSS, and hours to MRI were collected. Patients with a nonlacunar middle cerebral artery (MCA) territory infarct and MRI less than 48 hours from symptom onset were included (n= 143). A multivariable linear regression model was constructed to determine independent predictors of smaller infarct volume. Results. A total of 143 patients were studied, including 38 patients taking statins at the time of their stroke. In univariate analysis, patients using statins were significantly more likely to have a history of hyperlipidemia, atrial fibrillation, and coronary artery disease and to be using coumadin, antiplatelet drugs, and angiotensin-converting enzyme inhibitors. Patients on statins had a tendency toward smaller infarcts in univariate analysis (median 25.4 cm.sup.3 vs. 15.5 cm.sup.3, P= 0.054). In multivariable linear regression analysis statin use, patient age, and TIA within the prior 4 weeks were independently associated with smaller DWI volumes; vessel occlusion on vascular imaging, and cardioembolic stroke subtype with larger infarct size. Conclusions. Statin use prior to the onset of nonlacunar MCA infarction was associated with a smaller infarct volume independent of other factors. Further studies utilizing both clinical and radiologic outcomes will be required to confirm these findings. Author Affiliation: (1)From the Department of Neurology, The Cleveland Clinic Foundation, Cleveland, OH (SS); Department of Neurology, Section of Stroke and Neurocritical Care, Cleveland, OH (NV, IK, DK); Department of Neurology, Stroke Institute, University of Pittsburgh Medical Center, Pittsburgh, PA (NV); and Department of Radiology, Section of Neuroradiology, Cleveland, OH (AT), Department of Neurology, Division of Cerebrovasoular Diseases and Neuroendovascular Services, Michigan State University, East Lansing, MI (RG). Article History: Received March 14, 2006, and in revised form July 19, 2006. Accepted for publication July 25, 2006. Article note: Address correspondence to Derk W. Krieger, MD, PhD, Department of Neurology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, S-90, Cleveland, OH 44195. E-mail: krieged@ccf.org.

Byline: Sujay. Sada, Yugandhar. Reddy, Sampath. Rao, Suvarna. Alladi, Subash. Kaul Introduction: Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a [...]

Byline: Jing. Zhitao, Wang. Yibao, Wu. Anhua, Ou. Shaowu, Ban. Yunchao, Zhou. Renyi, Wang. Yunjie Background: Aneurysms arising from the P[sub] 2 segment of the posterior cerebral artery (PCA) are [...]

Byline: S. Pai, R. Varma, R. Kulkarni Background: The microsurgical anatomy of the middle cerebral artery (MCA) is of particular interest to the cerebrovascular surgeon. The purpose of this study [...]