Preexisting statin use is associated with greater reperfusion in hyperacute ischemic stroke.

Background And Purpose: Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins.

Noninvasive detection of brainstem and spinal cord axonal degeneration in an amyotrophic lateral sclerosis mouse model.

Degeneration of motor neurons and their associated axons is a hallmark of amyotrophic lateral sclerosis, but reliable noninvasive lesion detection is lacking. In vivo diffusion tensor imaging was performed to evaluate neurodegeneration in the brainstem and cervical spinal cord of wild-type and G93A-SOD1 transgenic mice, an animal model of amyotrophic lateral sclerosis. A statistically significant reduction in the apparent diffusion coefficient was observed in the motor nuclei VII and XII of G93A-SOD1 transgenic mice relative to wild-type mice.

Imaging of functional connectivity in the mouse brain.

Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms.

Early changes of tissue perfusion after tissue plasminogen activator in hyperacute ischemic stroke.

Background And Purpose: it is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome.

Methods: three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.

Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from 6-hydroxydopamine-induced neurotoxicity.

Aim Of The Study: Dangguijakyak-san (DJS) is a multi-herbal formula that has long been widely used in traditional Oriental medicine to treat gynecologic disorders, including neurological symptoms. Recent clinical and experimental studies have reported aging and anti-neurodegenerative effects of DJS. In this study, we evaluated the neuroprotective effects of DJS on dopaminergic (DA) neurons damaged by 6-hydroxydopamine (6-OHDA).

Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking.

Background: Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain.

Distance from home to hospital and thrombolytic utilization for acute ischemic stroke.

Treatment of acute stroke with thrombolytic therapy has been limited because of the narrow treatment window. Distance from home to hospital may affect arrival time and likelihood of receiving thrombolytic therapy for acute stroke. The present study included stroke subjects seen at Barnes Jewish Hospital in 2006-2007, residing in St Louis City/County, who were at home at the time of the stroke (n = 416).

Protective effect of Cyperi rhizoma against 6-hydroxydopamine-induced neuronal damage.

Cyperi rhizoma, the rhizome of Cyperus rotundus L. (Family Cyperaceae), is a well-known functional food and traditional herbal medicine in Korea. It has been reported that Cyperi rhizoma has antioxidant and free radical scavenging activities that play a major role in protection of neurodegenerative disorders, such as Parkinson's disease (PD).

Patent foramen ovale and stroke: Should PFOs be closed in otherwise cryptogenic stroke?

Since initial reports of its association with ischemic stroke appeared in 1988, there has been continued controversy regarding the existence and strength of the association between patent foramen ovale (PFO) and ischemic stroke. Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO, yet population-based studies have failed to confirm this association. Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO.

Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photoacoustic microscopy.

We report optical-resolution photoacoustic microscopy (OR-PAM) for in vivo imaging of amyloid plaques in an Alzheimer's disease mouse model. Validation using conventional fluorescence microscopy and multiphoton microscopy shows that OR-PAM has sufficient sensitivity and spatial resolution to identify amyloid plaques in living brains. In addition, with dual-wavelength OR-PAM, the three-dimensional morphology of amyloid plaques and the surrounding microvasculature are imaged simultaneously through a cranial window without angiographic contrast agents.

Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide.

One of the neuropathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque, primarily composed of aggregated amyloid-beta (Abeta) peptide. In vitro, Abeta(1-42), the major alloform of Abeta found in plaques, self-assembles into fibrils at micromolar concentrations and acidic pH. Such conditions do not exist in the extracellular fluid of the brain where the pH is neutral and Abeta concentrations are in the nanomolar range.

Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice.

Amyloid plaques are primarily composed of extracellular aggregates of amyloid-beta (Abeta) peptide and are a pathological signature of Alzheimer's disease. However, the factors that influence the dynamics of amyloid plaque formation and growth in vivo are largely unknown. Using serial intravital multiphoton microscopy through a thinned-skull cranial window in APP/PS1 transgenic mice, we found that amyloid plaques appear and grow over a period of weeks before reaching a mature size.

Therapeutic effects of Chiljehyangbuhwan on primary dysmenorrhea: a randomized, double blind, placebo-controlled study.

Objective: This clinical study was conducted to investigate the efficacy and safety of an oriental herbal medicine native to Korea, Chiljehyangbuhwan, in treating primary dysmenorrhea.

Design And Setting: A total of 100 primary dysmenorrhea patients who visited Kyung Hee University Korean Oriental Medicine Hospital between July 19 2004 and August 27 2004 were recruited. Secondary or drug-related dysmenorrhea was screened out through interviews and examination.

Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM.

Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abeta(1-42)), the most abundant Abeta peptide found in plaques, has a much greater propensity to self-aggregate into fibrils than the other peptides and is believed to be more pathogenic.

Resident-based acute stroke protocol is expeditious and safe.

Background And Purpose: The decision to administer tPA to acute stroke patients is frequently made by stroke attendings or fellows, but placing residents in this position may make tPA delivery more efficient.

Methods: Beginning in 2004, we instituted a resident-based acute stroke protocol placing neurology residents in decision-making roles. Time-intervals, symptomatic hemorrhage rate, and discharge locations were prospectively collected and compared between two epochs, before and after 2004.

Cerebral amyloid angiopathy: progressive disruption of the neurovascular unit.

Cellular elements of the neurovascular unit are essential for the physiological functioning of brain vessels. If any of these vascular elements are disturbed the consequences can be dire. Cerebral amyloid angiopathy (CAA), a disorder caused by the accumulation of amyloid in cerebral vessels, provides a case study of progressive neurovascular unit dysfunction leading to failure of vascular reactivity, smooth muscle cell loss, and eventual frank breakdown of vessel integrity resulting in recurrent and sometimes fatal intracerebral hemorrhage.

The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients.

Background: Definitive diagnosis of Alzheimer disease (AD) can be made only by histopathological examination of brain tissue, prompting the search for premortem disease biomarkers. We sought to determine if the novel brain injury biomarker, visinin-like protein 1 (VLP-1), is altered in the CSF of AD patients compared with controls, and to compare its values to the other well-studied CSF biomarkers 42-amino acid amyloid-beta peptide (Abeta(1-42)), total Tau (tTau), and hyperphosphorylated Tau (pTau).

Methods: Using ELISA, we measured concentrations of Abeta(1-42), tTau, pTau, and VLP-1 in CSF samples from 33 AD patients and 24 controls.

ZnO nanotips and nanorods on carbon nanotube/Si substrates: anomalous p-type like optical properties of undoped ZnO nanotips.

ZnO nanotips and nanorods were grown on screen-printed multi-walled carbon nanotube (MWCNT) films via thermal chemical vapor deposition at relative low growth temperatures of 400 and 500 °C. Uniform formation of ZnO nanotips and nanorods occurred on MWCNT-printed Si substrates, but were rarely observed on bare Si substrates at the same growth temperatures. In photoluminescence (PL) measurements, it was found that ZnO nanorods exhibit typical intrinsic optical properties, while ZnO nanotips revealed p-type like luminescence behavior.

Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta.

Cerebral deposition of beta-amyloid (Abeta) peptides is a pathological hallmark of Alzheimer disease. Intramembranous proteolysis of amyloid precursor protein by a multiprotein gamma-secretase complex generates Abeta. Previously, it was reported that CD147, a glycoprotein that stimulates production of matrix metalloproteinases (MMPs), is a subunit of gamma-secretase and that the levels of secreted Abeta inversely correlate with CD147 expression.

Methylprednisolone protects oligodendrocytes but not neurons after spinal cord injury.

Methylprednisolone (MP) is used to treat a variety of neurological disorders involving white matter injury, including multiple sclerosis, acute disseminated encephalomyelitis, and spinal cord injury (SCI). Although its mechanism of action has been attributed to anti-inflammatory or antioxidant properties, we examined the possibility that MP may have direct neuroprotective activities. Neurons and oligodendrocytes treated with AMPA or staurosporine died within 24 h after treatment.

Expression profiling identifies a molecular signature of reactive astrocytes stimulated by cyclic AMP or proinflammatory cytokines.

Specialized glia, termed reactive astrocytes, accompany numerous pathologic conditions affecting the central nervous system, including stroke, multiple sclerosis, and neoplasia. To better define this important cell type, we employed high-density microarray gene expression profiling using two in vitro models of reactive gliosis (stimulation with dbcAMP or IL-1beta/IFNgamma). We identified 44 differentially expressed transcripts common to both in vitro models and demonstrated that a subset of these genes are also differentially expressed in response to experimental autoimmune encephalomyelitis and focal cerebral ischemia in vivo.

Erythropoietin and its carbamylated derivative prevent the development of experimental diabetic autonomic neuropathy in STZ-induced diabetic NOD-SCID mice.

Autonomic neuropathy is a significant diabetic complication resulting in increased morbidity and mortality. Studies of autopsied diabetic patients and several rodent models demonstrate that the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in prevertebral ganglia is the occurrence of synaptic pathology resulting in distinctive dystrophic neurites ("neuritic dystrophy"). Our prior studies show that neuritic dystrophy is reversed by exogenous IGF-I administration without altering the metabolic severity of diabetes, i.

Vascular permeability precedes spontaneous intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats.

Background And Purpose: Stroke-prone spontaneous hypertensive rats (SHRsp) fed a high-salt diet develop malignant hypertension, blood-brain barrier breakdown, and spontaneous intracerebral hemorrhage (ICH). The precise spatial and temporal relationship between these events has not been well-delineated.

Methods: Ten SHRsp male rats, fed a high-salt diet, were imaged weekly using MRI, starting at 12 weeks of age.

Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes.

Seizures may exert pathophysiological effects on dendritic spines, but the molecular mechanisms mediating these effects are poorly understood. Actin represents a major structural protein of dendritic spines, and actin filaments (F-actin) can be depolymerized by the regulatory molecule, cofilin, leading to structural or functional changes in spines in response to normal physiological activity. To investigate mechanisms by which pathophysiological stimuli may affect dendritic spine structure and function, we examined changes in F-actin and cofilin in hippocampus due to 4-aminopyridine (4-AP)-induced seizures/epileptiform activity in vivo and in vitro and investigated possible structural correlates of these changes in actin dynamics.

Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism.

It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) may result from an imbalance between the generation and clearance of the amyloid-beta peptide (Abeta). Although familial AD appears to be caused by Abeta overproduction, sporadic AD (the most prevalent form) may result from impairment in clearance. Recent evidence suggests that several proteases may contribute to the degradation of Abeta.