Plaque Vulnerability in Internal Carotid Arteries with Positive Remodeling

Background: This study aimed to evaluate the efficacy of assessing positive remodeling for predicting future stroke events in the internal carotid artery. We therefore assessed narrowing of the carotid artery lumen using multidetector-row computer tomography (MDCT) angiography and carotid plaque characteristics using black-blood (BB) magnetic resonance (MR). Methods: We retrospectively selected 17 symptomatic and 11 asymptomatic lesions with luminal narrowing >50%. We compared remodeling parameters of luminal stenosis (remodeling ratio, RR/remodeling index, RI) using MDCT and MR intensities of atherosclerotic plaque contents using the BB technique (relative signal intensity, rSI). We also confirmed the validity of the relationship between MR intensity and atherosclerotic plaque contents by histology. The levels of biological markers related to vessel atherosclerosis were measured. Results: Plaque lesions with positive remodeling in carotid arteries were associated with a significantly higher prevalence of stroke compared with plaques with negative remodeling (p Conclusions: The results of this study suggest that the combined analysis of RR, RI and rSI could potentially help to predict future stroke events

Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting.</p> <p>Results</p> <p>Here, we demonstrate that minocycline attenuates both <it>in vitro </it>(oxygen glucose deprivation) and <it>in vivo </it>(middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury.</p> <p>Conclusion</p> <p>The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.</p

Changes in Striatal Dopamine Release Associated with Human Motor-Skill Acquisition

The acquisition of new motor skills is essential throughout daily life and involves the processes of learning new motor sequence and encoding elementary aspects of new movement. Although previous animal studies have suggested a functional importance for striatal dopamine release in the learning of new motor sequence, its role in encoding elementary aspects of new movement has not yet been investigated. To elucidate this, we investigated changes in striatal dopamine levels during initial skill-training (Day 1) compared with acquired conditions (Day 2) using 11C-raclopride positron-emission tomography. Ten volunteers learned to perform brisk contractions using their non-dominant left thumbs with the aid of visual feedback. On Day 1, the mean acceleration of each session was improved through repeated training sessions until performance neared asymptotic levels, while improved motor performance was retained from the beginning on Day 2. The 11C-raclopride binding potential (BP) in the right putamen was reduced during initial skill-training compared with under acquired conditions. Moreover, voxel-wise analysis revealed that 11C-raclopride BP was particularly reduced in the right antero-dorsal to the lateral part of the putamen. Based on findings from previous fMRI studies that show a gradual shift of activation within the striatum during the initial processing of motor learning, striatal dopamine may play a role in the dynamic cortico-striatal activation during encoding of new motor memory in skill acquisition

Effect of dopaminergic medication on PAS-induced modulation of the MEP amplitude with PD-on and-off.

<p>In PD patients, the average MEP amplitude in the right APB was significantly elevated after dopaminergic medication (*<i>P</i><0.05).</p

Patient demographic and clinical details.

<p>Patient demographic and clinical details.</p

Mean pinching force changes in initial skill-training on Day 1 and mean acceleration changes in prepractice on Day 2.

<p>(A) Changes of the mean pinching force in the initial skill training between baseline (before session 1) and post session 3. Y axis indicates mean pinching force (kg). Error bars show the SD. *<i>P</i><0.05. (B) Mean accelerations in the motor prepractice between block 1 and block 4. Y axis indicates mean accelerations (cm/s²). Error bars show the SEM. N.S. not significant.</p

Experimental procedures.

<p>(A) Time schedule of experiments. Subjects were scanned for evaluating striatal dopamine levels using ¹¹C-raclopride PET on Day 1 (initial skill-training condition) and Day 2 (acquired condition). (B) ¹¹C-raclopride PET scanning. ¹¹C-raclopride (555 MBq) was injected into the right vein just before the emission data was acquired. They practiced rapid contraction of their left thumb via visual feedback during PET scanning. (C) Display seen by subjects during motor practice. Three coloured horizontal lines were graphically presented to help subjects understand the quality of their performance: peak acceleration of the present movement (blue), mean peak acceleration of all previous trials within a block (green) and maximum peak acceleration of all previous trials within a block (red).</p

¹¹C-raclopride BP changes in sub-regions of the striatum between the two conditions.

<p>Left panel shows the grass brain map of the voxel-based analysis of ¹¹C-raclopride BP change (upper figure: initial skill-training condition < acquired condition and lower figure: acquired condition < initial skill-training condition). Right panel shows coronal and axial sections of the statistical parametric map of ¹¹C-raclopride BP change in the initial skill-training condition versus acquired condition overlaying the MRI T1 image in stereotaxic space. Right side image corresponds to right side brain. The displayed cluster shows the significant area of decreased ¹¹C-raclopride BP in the right antero-dorsal and lateral part of the putamen. The peak coordinate in the right putamen was located at X = 30, Y = 4, Z = 12. No BP change was observed in the left putamen.</p

Reduced Cholinergic Activity in the Hippocampus of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein Knockout Mice

The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei. HCNP is processed from the N-terminal region of a 186 amino acid, 21 kD HCNP precursor protein called HCNP-pp (also known as Raf kinase inhibitory protein (RKIP) and phosphatidylethanolamine-binding protein 1 (PEBP1)). In this study, we generated HCNP-pp knockout (KO) mice and assessed their cholinergic septo-hippocampal projection, local field potentials in CA1, and behavioral phenotypes. No significant behavioral phenotype was observed in HCNP-pp KO mice. However, theta power in the CA1 of HCNP-pp KO mice was significantly reduced because of fewer cholineacetyltransferase-positive axons in the CA1 stratum oriens. These observations indicated disruption of cholinergic activity in the septo-hippocampal network. Our study demonstrates that HCNP may be a cholinergic regulator in the septo-hippocampal network