During a median follow-up of 2.7 years, 110 adults

(16.5%) had cognitive decline. Among the measures of gait performance (speed, step length, and frequency), step length AZD6094 supplier was the most predictive of cognitive decline. After controlling for important confounders, older men in the lowest and middle tertiles of step length at maximum speed and older women in the lowest and middle tertiles of step length at usual speed were 4.42 (95% confidence interval: 1.65-11.8), 2.17 (0.82-5.71), 5.76 (2.15-15.4), and 2.44 (0.94-6.35) times as likely to develop cognitive decline, respectively, as those of the same sex and walking speed who were in the highest tertile.

Step length was an independent predictor of cognitive decline in a general population of older adults and may be a better predictor than overall gait speed of such decline.”
“Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are PD98059 supplier associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of fosB, an immediate

early gene encoding FosB and Delta FosB/Delta 2 Delta FosB by alternative splicing and translation initiation, is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus, following transient forebrain ischemia in the rat brain. Moreover,

adenovirus-mediated expression of fosB gene products can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive IMP dehydrogenase behavior, suggesting impaired neurogenesis in fosB-null mice. In the current study, we analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosB(d/d) mice that express Delta FosB/Delta 2 Delta FosB but not FosB, in comparison with wild-type mice, alongside neuropathology, behaviors, and gene expression profiles. fosB-null but not fosB(d/d) mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression, and epilepsy were altered in the hippocampus of fosB-null mice. Thus, we conclude that the fosB-null mouse is the first animal model to provide a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB. Neuropsychopharmacology (2013) 38, 895-906; doi: 10.1038/npp.2012.260; published online 16 January 2013″
“The aim of the present study was to investigate the prevalence of hypotension in older participants and to identify which 24-hour ambulatory blood pressure monitoring parameter better correlated with the occurrence of hypotension.

We studied 588 elderly participants (mean age 78.7 +/- 7.

Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December,

2009, and August, 2010. Households and individuals delivering buy BAY 1895344 the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6-12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849.

Findings 1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0-4 years with birth certificates had increased by 1.5% (95% CI -7.1 to 10.1) in the UCT group

and by 16.4% (7.8-25.0) in the CCT group by the end of the intervention period. The proportions of children aged 0-4 years with complete vaccination records was 3.1% (-3.8 to 9.9) greater in the UCT group and 1.8% (-5.0 to 8.7) greater in the CCT group than in the control group. The proportions of children aged 6-12 years who attended school at least 80% of the time was 7.2% (0.8-13.7) higher in the UCT group and PLX3397 datasheet 7.6% (1.2-14.1) in the CCT group than in the control group.

Interpretation Our results support strategies to integrate cash transfers into social welfare selleck kinase inhibitor programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and

CCT programmes in this region.”
“Studies of socially housed rodents have provided significant information regarding the mechanisms of stress and of stress-related disorders.

Since psychosocial stress is known to alter the functional activity of dopaminergic system, we employed amphetamine (AMP) to evaluate the involvement dopamine in mediating the behavioral consequences of psychosocial stress.

Male rats housed two per cage were designated as dominant (DOM) or subdominant (Sdom) based on initial evaluations of agonistic behaviors and body weight changes. Diad-housed rats and a group of single-housed (SiH) rats were tested in an open field after injections of saline or amphetamine (0.9 or 2.7 mg/kg IP) prior to and again while diad-housing.

Compared to future DOM rats, saline-injected future Sdom rats entered the open field center less frequently, spent less time in rearing behavior and groomed less. At the pre-diad test AMP treatment elevated locomotor activity of all rats, while stimulation of center entries was more marked in future DOM rats. At the diad test, AMP’s locomotor stimulant effect was evident in all experimental groups with DOM rats showing higher effects compared to Sdom and SiH rats.

These data indicated a genetic mechanism for normal variation in human memory and suggest effects RepSox chemical structure of BDNF signaling on hippocampal function in humans. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“In the current perception of the herpesvirus replication cycle,

two fusion processes are thought to occur during entry and nuclear egress. For penetration, glycoproteins gB and gH/gL have been shown to be essential, whereas a possible role of these glycoproteins in nuclear egress remains unclear. Viral envelope glycoproteins have been detected by immunolabeling in the nuclear membrane as well as in primary enveloped particles in several herpesviruses, indicating that Selleckchem Alpelisib they might be involved in the fusion process. Moreover, a herpes simplex virus type I mutant simultaneously lacking gB and gH was described to be deficient in nuclear egress (A. Farnsworth, T. W. Wisner, M. Webb, R. Roller, G. Cohen, R. Eisenberg, and D. C. Johnson, Proc. Natl. Acad. Sci. USA 104:10187-10192, 2007). To analyze the situation in the related

alphaherpesvirus,pseudorabies virus (PrV), mutants carrying single and double deletions of glycoproteins gB, gD, gH, and gL were constructed and characterized. We show here that the simultaneous deletion of gB and gD, gB and gH, gD and gH, or gH and gL has no detectable effect on PrV egress, implying that none of these glycoproteins either singly or in the tested combinations ADAM7 is required for nuclear egress. In addition, immunolabeling studies using different mono- or polyclonal sera raised against various PrV glycoproteins did not reveal the presence of viral glycoproteins in the inner nuclear membrane or in primary virions. Thus, our data strongly suggest that different fusion mechanisms are active during virus entry and egress.”
“We have examined the ultrastructure of the myenteric ganglion of the subdiaphragmatic esophagus and determined whether the ganglion neurons receive direct

projections from the dorsal motor nucleus of the vagus (DMV) using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) as an anterograde tracer. The neurons (22.2 mu m x 13.3 mu m) of myenteric ganglion in the esophagus contained dark cytoplasm having many free ribosomes, mitochondria, and an oval nucleus, and received only a few axon terminals contacting somata. All axon terminals formed asymmetric synaptic contacts with dendrites or somata. Approximately 85% of the axon terminals contacting dendrites and about 50% of the axon terminals contacting somata contained pleomorphic vesicles, while the rest contained round synaptic vesicles. When WGA-HRP was injected into the DMV, anterogradely labeled fibers and terminals were found in the myenteric ganglia. The WGA-HRP labeled terminals were large (1.97 mu m) and contained round clear vesicles and small granular vesicles. These labeled terminals contacted exclusively the small dendrites, but not the somata.

Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 mu M, a range measured in human abusers. With larger METH doses, progressive increases

in abnormal behavior and decreases in social behavior were observed on ‘injection’ days. Anxiety increased on ‘no injection’ days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem JSH-23 concentration analysis of METH brains showed 20% lower striatal DA content while

autoradiography studies of precommissural striatum showed 35% lower [H-3]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [H-3] dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [H-3]SCH 23390 and [H-3]raclopride binding to DA D1 and D2 receptors, respectively. Selleckchem PRN1371 Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.”
“Variola virus, the causative agent of smallpox, encodes a soluble complement regulator named SPICE. Previously, SPICE has been shown to be much more potent in inactivating human

complement than the vaccinia virus complement control protein (VCP), although they differ only in 11 amino acid residues. In the present study, we have expressed SPICE, VCP, and mutants of VCP by substituting each or more of the 11 non-variant VCP residues with the corresponding residue of SPICE to identify hot spots that GNA12 impart functional advantage to SPICE over VCP. Our data indicate that (i) SPICE is similar to 90-fold more potent than VCP in inactivating human CA, and the residues Y98, Y103, K108 and K120 are predominantly responsible for its enhanced activity; (ii) SPICE is 5.4-fold more potent in inactivating human C4b, and residues Y98, Y103, K108, K120 and L193 mainly dictate this increase; (iii) the classical pathway decay-accelerating activity of activity is only twofold higher than that of VCP, and the 11 mutations in SPICE do not significantly affect this activity; (iv) SPICE possesses significantly greater binding ability to human CA compared to VCP, although its binding to human C4b is lower than that of VCP; (v) residue N144 is largely responsible for the increased binding of SPICE to human C3b; and (vi) the human specificity of SPICE is dictated primarily by residues Y98, Y103, K108, and K120 since these are enough to formulate VCP as potent as SPICE.

The distributions of H3-K4 mono-, di-, and tri-methylation exhibited EPZ6438 exactly the same pattern as LSD1. LSD1 expression was induced both region and cell specifically after ischemic/perfusion, and complied with the two-peak mode of expression.

These studies revealed a tightly regulated distribution for LSD1 in the brain

of rats under ischemic insult, suggesting a critical role in neuron function. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society All rights reserved.”
“The envelope of the human hepatitis B virus (HBV) contains three membrane proteins (L, M, and S). They accomplish different functions in HBV infectivity and nucleocapsid envelopment. Infectivity determinants have been assigned to the N-terminal part of the pre-S1 domain of the L protein and the antigenic loop of the S domain in the L and/or S protein. Nucleocapsid envelopment requires a C-terminal sequence within pre-S1, including

the five N-terminal amino acids of pre-S2 as part of the L protein. However, the role of the M protein and the pre-S2 domain of the L protein are not entirely understood. We addressed this question and analyzed assembly competence and infectivity of viruses that lack the M protein and, at the same CP-868596 clinical trial time, carry alterations in the pre-S2 domain of L. These include deletions, in part frameshift mutations and a randomization of virtually the entire pre-S2 sequence. We found that the M protein is dispensable for HBV in vitro infectivity.

Viruses that lack the M protein and contain a mostly randomized pre-S2 sequence assemble properly and are infectious in HepaRG cells and primary human hepatocytes. While deletions of 20 amino acids in the pre-S2 domain of L protein allowed the production of infectious virions, more extended deletions interfered with assembly. This indicates that the pre-S2 domain of the L protein serves an important role for virus assembly, presumably as a spacer that supports conformational changes of L protein but does not participate as part of the M protein or as a subdomain of the L protein in virus entry.”
“The human cerebral neocortex is divided into Regorafenib price six layers consisting of specific neuronal cell types and connections To determine the distribution of cortical neurons during early development, we examined the expressions of layer-specific markers in human midterm fetal brains Layer V marker ZNF312 is expressed in most cortical areas, but not in the prospective somatosensory association area. Expression of layer IV marker ROR beta is also diminished in this region but Increased in the primary visual cortex, where expression of ZNF312 is reduced. Our results indicate that ZNF312 and other layer markers have area dependent expressions in the human fetal cortex (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Bats are the second largest group of mammals on earth and act as reservoirs of many emerging viruses.

Thus, the cell will take the death fate if it cannot recover from the damage within a time period that is inversely proportional to the damage level. This “”adaptive timer”" strategy is likely to be adopted in other stress response systems. (C) 2010 Elsevier Ltd. All

rights reserved.”
“Cell transplantation has been shown to be an effective therapy for central nervous system disorders in animal models. Improving the efficacy of cell transplantation depends critically on improving grafted cell survival. We investigated whether glial cell line-derived neurotrophic factor (GDNF)-pretreatment of neural stem cells (NSCs) enhanced grafted cell survival in a rat model of Parkinson’s disease (PD). We first examined the neuroprotective

effects of GDNF on oxygen-glucose deprivation Ruxolitinib cell line (OGD) in NSCs. Cells were pretreated with GDNF for 3 days before subjecting them to OGD. After 12 h of OGD, GDNF-pretreated NSCs showed significant increases in JNK-IN-8 survival rates compared with PBS-pretreated NSCs. An apoptosis assay showed that the number of apoptotic cells was significantly decreased in GDNF-pretreated NSCs at 1 h and 6 h after OGD. A PD rat model was then established by unilateral injection of 6-hydroxydopamine (6-OHDA, 9 pig) into the medial forebrain bundle. Two weeks after 6-OHDA injection, GDNF-pretreated NSCs, PBS-pretreated NSCs, or PBS were injected into PD rat striatum. The survival of grafted cells in the striatum was significantly increased these in the GDNF-pretreated NSC group compared with the control groups. GDNF pretreatment increased survival of NSCs following transplantation,

at least partly through suppression of cell apoptosis. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Crassostrea oysters are protandrous hermaphrodites. Sex is thought to be determined by a single gene with a dominant male allele M and a recessive protandrous allele F, such that FF animals are protandrous and MF animals are permanent males. We investigate the possibility that a reduction in generation time, brought about for example by disease, might jeopardize retention of the M allele. Simulations show that ME males have a significantly lessened lifetime fecundity when generation time declines. The allele frequency of the M allele declines and eventually the M allele is lost. The probability of loss is modulated by population abundance. As abundance increases, the probability of M allele loss declines. Simulations suggest that stabilization of the female-to-male ratio when generation time is long is the dominant function of the M allele. As generation time shortens, the raison d’etre for the M allele also fades as mortality usurps the stabilizing role. Disease and exploitation have shortened oyster generation time: one consequence may be to jeopardize retention of the M allele.

Mice heterozygous for a disruption in exon 7 of the Nrg1 gene lack Type III (cysteine-rich-domain-containing) isoforms and CYC202 supplier have sensorimotor gating deficits that may involve changes in the activity of a circuit involving projections from the ventral hippocampus (vHPC) to medium spiny neurons in

the nucleus accumbens (nACC). To explore the neural basis of these deficits, we examined electrophysiological activity in the nACC and vHPC of these mice. Under urethane anesthesia, bursts of spontaneous activity propagated from the vHPC to the nACC in both wild-type and mutant mice. However, these bursts were weaker in mutant nACC, with reduced local field potential amplitude and spiking activity. Single units in mutant nACC fired less frequently within the bursts, and more frequently outside

of the bursts. Moreover, within-burst nACC spiking was less modulated by vHPC activity, as determined by phase-locking to the low-frequency oscillatory components of the bursts. These data suggest that the efficacy of vHPC input to the nACC is reduced in the Type III Nrg1 heterozygotes, supporting a role LB-100 mouse for Nrg1 in the functional profile of hippocampal-accumbens synapses. Neuropsychopharmacology (2011) 36, 488-496; doi:10.1038/npp.2010.180; published online 6 October 2010″
“Aims:

To investigate the in vitro antiherpes Pomalidomide research buy effects of the crude aqueous extract obtained from Cecropia glaziovii leaves and their related fractions, the n-butanol fraction (n-BuOH) and the C-glycosylflavonoid-enriched fraction (MeOH(AMB)), and to determine the viral multiplication step(s) upon which this C-glycosylflavonoid-enriched fraction acts.

Methods and Results:

The antiviral activity was evaluated against human herpes virus types 1 and 2 (HHV-1, HHV-2) by plaque reduction assay.

The mode of action of the most active fraction was investigated by a set of assays, and the results demonstrated that MeOH(AMB) fraction exerts anti-herpes action by the reduction of viral infectivity (only against HHV-2); by the inhibition of virus entry into cells; by the inhibition of cell-to-cell virus spread as well as by the impaired levels of envelope proteins of HHV-1. The high-performance liquid chromatography (HPLC)-photo-diode array (PDA) analysis showed that the C-glycosylflavonoids are the major constituents of this fraction.

Conclusions:

These data showed that the MeOH(AMB) fraction has an antiviral activity against HHV types 1 and 2. The C-glycosylflavonoids are the major constituents of this fraction, which suggests that they could be one of the compounds responsible for the detected anti-herpes activity.

Copyright (C) 2010 S. Karger AG, Basel”
“Motivational biases and spatial attention

both modulate neural activity and influence behavioural performance. The time course of motivational bias effects, as well as the relationship between motivation and attention across the time course of information processing, however, are relatively unknown. In the present study, event-related potentials (ERPs) were recorded whilst individuals performed a modified Posner task, in which cue stimuli indicated the reward stakes of a given trial and the probable spatial location of a subsequent target stimulus. Reaction times (RTs) were sensitive to motivation and to attention, with faster responses produced

Mocetinostat solubility dmso on valid and on rewarded trials. In addition, motivation modulated neural activity from the visual analysis of stimuli, with an earlier N1 peak for rewarded compared with Savolitinib cell line non-rewarded stimuli. Effects of motivation were relatively independent from those of attention until late cognitive processing and response production, where motivation and attention interacted to enhance P300-like potentials and the lateralised readiness potential (LRP). The results suggest that multiple sources of modulatory influences may exist, with motivation and attention exerting independent influences over early stimulus and cognitive processing, followed by a late interaction allowing the construction Idoxuridine of a comprehensive stimulus representation that contains information pertaining to both motivational and spatial expectations. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background/Aims: The mechanisms that regulate the size-related morphologies of various blood vessels from the aorta to capillary

vessels are still poorly understood. In this study, we evaluate the involvement of regulator of calcineurin 1 (RCAN1), a regulatory protein in the calcineurin/NFAT signal transduction pathway, in vascular morphology to gain further insight into these mechanisms. Methods and Results: We first generated 2 types of vasculature in vitro from the same source of human umbilical vein endothelial cells by fibrin gel assay. We found that RCAN1 was significantly up-regulated in large vessels with low branching frequencies when compared with small vessels with high branching frequencies. Next, to clarify whether RCAN1 regulates the branching of blood vessels in vivo, we injected RCAN1 mRNA into fertilized Xenopus laevis eggs. Overexpression of RCAN1 decreased the number of branching points that sprouted from intersomitic vessels during X. laevis angiogenesis. In addition, coexpression of calcineurin A, a target of RCAN1,could rescue RCAN1-suppressed vascular branching.

Allocation was by block randomisation stratified

PKC inhibitor by Centre and time from unprotected sexual intercourse to treatment, with allocation concealment by identical opaque boxes labelled with a unique treatment number. participants were masked to treatment assignment whereas investigators were not. Follow-up was done 5-7 days after expected onset of next menses. The primary endpoint was pregnancy rate in women who received emergency contraception within 72 h of unprotected sexual intercourse, with a non-inferiority margin of 1% point difference between groups (limit of 1.6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those aged over 35 years, women with unknown

follow-up pregnancy status, and those who had re-enrolled in the study. Additionally, we undertook a meta-analysis of our Bcl-2 inhibitor trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel. This trial is registered with ClinicalTrials.gov, number NCT00551616.

Findings In the efficacy-evaluable population, 1696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n=844; levonorgestrel, n=852). There were 15 pregnancies in the ulipristal acetate group (1.8%, 95% CI 1.0-3.0) and 22 in the levonorgestrel group (2.6%, 1.7-3.9; odds ratio [OR] 0.68, 95% CI 0.35-1.31). In 203 women who received emergency contraception between 72 In and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse PAK6 event was headache (ulipristal acetate, 213 events [19.3%] in 1104 women; levonorgestrel, 211 events [18.9%] in 1117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis

(0-72 h), there were 22 (1.4%) pregnancies in 1617 women in the ulipristal acetate group and 35 (2.2%) in 1625 women in the levonorgestrel group (OR 0.58, 0.33-0.99; p=0.046).

Interpretation Ulipristal acetate provides women and health-care providers with an effective alternative for emergency contraception that can be used up to 5 days after unprotected sexual intercourse.

Funding HRA Pharma.”
“5-HT1A receptors mediate some effects of atypical antipsychotic drugs, such as the increase in cortical dopaminergic function, an effect likely related to the superior efficacy of these drugs on negative symptoms and cognitive deficits of schizophrenia. To examine whether 5-HT1A receptors are involved in the therapeutic action of clozapine (Clz) on positive symptoms, here we examined the ability of Clz to antagonize the behavioural syndrome induced by the non-competitive N-methyl-D-aspartate receptor antagonist, MK-801 in wild-type (WT) and 5-HT1A-receptor knockout (KO1A) mice.

gov, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Search terms were thoracic aortic trauma, traumatic thoracic aortic injury, traumatic DZNeP nmr aortic rupture, stent graft repair, and endovascular repair. Outcomes analyzed were procedure-related mortality, overall 30-day mortality, and paraplegia/paraparesis rate using odds ratios (OR) and 95% confidence intervals (CI). Publication bias was

investigated using funnel plots. Assessment of homogeneity was performed using the Q test; statistical heterogeneity was considered present at P < .05. Weighted averages of age, interval to repair, and injury severity score were compared with the Welch t test; P < .05 was considered statistically significant.

Results: Seventeen retrospective cohort studies from 2003 to 2007 were included. All were nonrandomized;

no prospective randomized trials were found. These studies reported oil 589 patients; 369 were treated https://www.selleckchem.com/products/pu-h71.html with open repair, and 220 underwent thoracic stent graft placement. There was no significant difference in age (mean 38.8 years for both) or interval to repair (mean 1.5 days for endoluminal repair; I day for open repair). Injury severity score was higher for patients undergoing endoluminal repair (mean, 42.4 vs 37.4 for open repair, P < .001). Procedure-related mortality was significantly lower with endoluminal repair (OR, 0.31; 95% CI, 0.15-0.66; P = .002). Overall 30-day mortality was also lower after endoluminal Progesterone repair (OR, 0.44; 95% CI, 0.25-0.78; P = .005). Sixteen studies reported data for postoperative paraplegia; 215 patients were treated with endograft placement and 333 with open repair. The risk of postoperative paraplegia was significantly less with endoluminal repair (OR, 0.32; 95% CI, 0.1-0.93; P = .037). The Q test did not indicate significant heterogeneity for the outcomes of interest; publication bias was limited.

Conclusions: Meta-analysis of retrospective cohort studies indicates that endovascular treatment of descending thoracic aortic trauma is an alternative to open repair and is associated with lower postoperative mortality

and ischemic spinal cord complication rates. (J Vasc Surg 2008;48:1343-51.)”
“Vascular endothelial growth factor (VEGF) may mediate increases in vascular permeability and hence plasma extravasation and edema following cerebral ischemia. To better define the role of VEGF in edema, we examined the effectiveness of a novel small molecule KDR kinase inhibitor Compound-1 in reducing edema and infarct volume following focal cerebral ischemia in studies utilizing treatment regimens initiated both pre- and post-ischemia, and with study durations of 24-72 h. Rats were subjected to 90 min of middle cerebral artery Occlusion (MCAO) followed by reperfusion. Pretreatment with Compound-1 (40 mg/kg p.o.) starting 0.5 h before Occlusion significantly reduced infarct volume at 72 h post-MCAO (vehicle, 194.1 +/- 22.9 mm(3) VS. Compound-1, 127.