Medicine and Health Sciences Commons^™

Defining Behavioral And Molecular Differences Between Summer And Migratory Monarch Butterflies, Haisun Zhu, Robert Gegear, Amy Casselman, Sriramana Kanginakudru, Steven Reppert

Robert J. Gegear

BACKGROUND: In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. RESULTS: Here we show that increasing juvenile hormone activity to induce summer-like …

Differential Effects Of Egf And Tgf-Beta1 On Fibroblast Activity In Fibrin-Based Tissue Equivalents, Jaime Grouf, Angela Throm, Jenna Balestrini, Katie Bush, Kristen Billiar

Kristen L. Billiar

Transforming growth factor-beta1 (TGF-beta1) is commonly used to promote matrix production for engineered tissues in vitro, yet it also enhances fibroblast contractility. For applications where contraction is undesirable, we hypothesized that epidermal growth factor (EGF) would yield equivalent mechanical properties without enhancing contractility. In this study, the response of human dermal fibroblasts to EGF (5 ng/mL) and TGF-beta1 (5 ng/mL) was determined within hemispheric fibrin-based gels by assessing matrix compaction and strength, cell number, collagen production, and contractility. After 3 weeks, both cytokines enhanced compaction relative to controls, and EGF roughly doubled matrix strength over controls and TGF-beta1-treated samples. TGF-beta1 …

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …

Association Between Chlorinated Pesticides In The Serum Of Prepubertal Russian Boys And Longitudinal Biomarkers Of Metabolic Function, Jane Burns, Paige Williams, Susan Korrick, Russ Hauser, Oleg Sergeyev, Boris Revich, Thuy Lam, Mary Lee

Mary M. Lee

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass …

Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger

Nils Henninger

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated …

Characterizing Tissue Fate After Transient Cerebral Ischemia Of Varying Duration Using Quantitative Diffusion And Perfusion Imaging, Juergen Bardutzky, Qiang Shen, Nils Henninger, Stefan Schwab, Timothy Duong, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of reperfusion on ischemic lesion evolution and pixel-by-pixel apparent diffusion coefficient-cerebral blood flow (ADC-CBF) dynamics of core and mismatch tissues after 35, 60, and 95 minutes of transient focal ischemia in rats (n=28). METHODS: Serial diffusion-, perfusion-, and T2-weighted imaging were performed up to 24 hours. The evolution of the magnetic resonance image-derived lesion volume was investigated and ADC-CBF scatterplots were performed to prospectively characterize the ADC and CBF dynamics of core and mismatch tissues with different fates. For comparison, similar analysis was performed on a historical …

Comparison Of Ischemic Lesion Evolution In Embolic Versus Mechanical Middle Cerebral Artery Occlusion In Sprague Dawley Rats Using Diffusion And Perfusion Imaging, Nils Henninger, Kenneth Sicard, Karl Schmidt, Juergen Bardutzky, Marc Fisher

Nils Henninger

BACKGROUND AND PURPOSE: Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague Dawley rats after permanent suture MCAO (sMCAO; n=8) and embolic MCAO (eMCAO; n=8).

METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed up to 180 minutes after MCAO. ADC and CBF values within 5 different brain regions were analyzed. ADC and CBF lesion volumes were calculated by using previously …

Ischemic Lesion Volume Determination On Diffusion Weighted Images Vs. Apparent Diffusion Coefficient Maps, Bernt Bratane, Birgül Bastan, Marc Fisher, James Bouley, Nils Henninger

Nils Henninger

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride …

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 …

Differential Recovery Of Multimodal Mri And Behavior After Transient Focal Cerebral Ischemia In Rats, Kenneth Sicard, Nils Henninger, Marc Fisher, Timothy Duong, Craig Ferris

Nils Henninger

The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T(2)-weighted (T(2)WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n=6) or sham operation (n=6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T(2) lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride …