Neuroscience and Neurobiology Commons^™

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …

The Proteasome Inhibitor Velcade Reduces Infarction In Rat Models Of Focal Cerebral Ischemia, Nils Henninger, Kenneth Sicard, James Bouley, Marc Fisher, Nancy Stagliano

Nils Henninger

The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment …

Laser Doppler Flowmetry Predicts Occlusion But Not Tpa-Mediated Reperfusion Success After Rat Embolic Stroke, Nils Henninger, James Bouley, Bernt Bratane, Birgül Bastan, Meghan Shea, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Laser Doppler flowmetry (LDF) is increasingly used to assess adequate occlusion after embolic stroke (ES) in rats. METHODS: Employing LDF, relative regional cerebral blood flow (rCBF) was continuously monitored during the first 2 h following ES and correlated with 24 h 2,3,5-triphenyltetrazolium chloride (TTC)-staining of corrected infarct volume. In a preliminary experiment (n=18), it was demonstrated that rCBF-reduction to 37% or less of baseline correctly identified occlusion success in the suture middle cerebral artery occlusion (sMCAO) model. Using the same methodology, we then assessed whether LDF allowed for identification of animals with successful ES (experiment 2, n=26) …

Visualization Of Clot Lysis In A Rat Embolic Stroke Model: Application To Comparative Lytic Efficacy, Ronn Walvick, Bernt Bratane, Nils Henninger, Kenneth Sicard, James Bouley, Zhanyang Yu, Eng Lo, Xiaoying Wang, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2). METHODS: In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 muL in 250 muL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot …

Differences In Ischemic Lesion Evolution In Different Rat Strains Using Diffusion And Perfusion Imaging, Juergen Bardutzky, Qiang Shen, Nils Henninger, James Bouley, Timothy Duong, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging.

METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after …

Normobaric Hyperoxia And Delayed Tpa Treatment In A Rat Embolic Stroke Model, Nils Henninger, Bernt Bratane, Birgül Bastan, James Bouley, Marc Fisher

Nils Henninger

In a rat embolic stroke (eMCAO) model, the effects of 100% normobaric hyperoxia (NBO) with delayed recombinant tissue plasminogen activator (tPA) administration on ischemic lesion size and safety were assessed by diffusion- and perfusion (PWI)-weighted magnetic resonance imaging. NBO or room air (Air) by a face mask was started at 30 mins posteMCAO and continued for 3.5 h. Tissue plasminogen activator or saline was started at 3 h posteMCAO. Types and location of hemorrhagic transformation were assessed at 24 h and a spectrophotometric hemoglobin assay quantified hemorrhage volume at 10 h. In NBO-treated animals the apparent diffusion coefficient/PWI mismatch persisted …