Abstract only Introduction: Cerebral ischemia can trigger cell death in the CA1 region of the hippocampus, an area important for memory. Protein kinase C epsilon (PKCε) activation prior to ischemia ...protects the CA1 from injury by modulating neurotransmission. The underlying mechanism needs further study. Hypothesis: PKCε-induced neuroprotection increases latency until anoxic depolarization (AD) through an activity-regulated cytoskeleton-associated protein (arc)-dependent mechanism of regulating AMPAR currents. Results: In vivo activation of PKCε by the PKCε-activator ψε-Receptor of Activated C Kinase (ψεRACK) increased BDNF 5.99 +/- 0.11 fold and TrkB phosphorylation levels 2.94 +/- 0.32 fold (enhancers of arc protein levels) (n = 4, p < 0.005, t-test). Arc mRNA and protein was increased 143.97 +/-7.68 % and 1.91 +/- 0.22 fold (n = 9, p < 0.005, t-test). Inhibition of arc using antisense oligodeoxynucleotides (arc AS ODNs) in cultured slices blocked PKCε-mediated neuroprotection against lethal oxygen and glucose deprivation (OGD) from 35.91 +/- 5.97 to 74.93 +/- 4.24 % cell death (n = 6, p < 0.005, ANOVA, Bonferroni). ΨεRACK decreased AMPAR-mediated mEPSC amplitude to 12.75 +/- 0.35 pA from 14.80 +/- 0.39 pA (n = 20, p < 0.01, ANOVA, Bonferroni). This effect was arc-dependent. Additionally, ψεRACK treatment increased latency until AD from 29.27 +/- 3.6 min 50.77 +/- 5.08 min (n = 13, p < 0.01, ANOVA, Bonferroni). This increase was arc-dependent, and required AMPAR internalization. Inhibiting internalization reduced AD latency from 54.5 +/- 8.40 min to 22.3 + 5.17 min (n = 6, p <0.005, t-test). Conclusion: Arc expression is necessary for neuroprotection afforded by PKCε-activation, modulates excitatory synaptic strength, and increases latency until AD. Methods: Western blot: Proteins (40 μg) were separated on a 12% SDS-PAGE gel. Immunofluorescence : 30 μm sections were incubated with 1:500 NeuN and 1:50 arc in PBS with 0.8% triton. Cultured slices preparation : sections from P9-11 rats were plated on inserts and cultured for 14 days. PI measurements of cell death : Slices were incubated in medium with 2 μg/mL PI. mEPSC measurements : Whole-cell voltage clamp was performed. AD: OGD, perfusate was switched to glucose free media, and bubbled with a 95% N 2 and 5% CO 2 gas.
Abstract only The majority of stroke patients suffer long-term disabilities impacting both motor and cognitive function. Physical exercise has been shown to improve functional recovery following ...focal cerebral ischemia by facilitating brain plasticity. However, the exercise intensity that promotes optimal cognitive recovery needs closer examination. This study seeks to analyze the effects of forced treadmill exercise at various speeds on spatial memory tests after focal ischemia in rats. We hypothesized that, a moderate intensity treadmill regiment will better ameliorate cognitive deficits and improve functional recovery after focal ischemia compared to the high or mild intensity groups. Three-month-old male Sprague Dawley rats were acclimated to the investigator and treadmill for three days. On day four, rats underwent focal cerebral ischemia using the middle cerebral artery occlusion model for 90 minutes or sham surgery and were randomly assigned to an exercise intensity group. Rats had three days of recovery post-surgery followed by forced treadmill exercise for six days. The rats were exposed to a two-minute warm-up period at 5 m/min and then exercised for a period of 30 minutes at 6 m/min for mild, 10 m/min for moderate, and 18 m/min for heavy. Finally, the rats were subjected to contextual fear conditioning where rats were placed in a fear conditioning chamber for 8 minutes with a 2 second 1.5 mA shock delivered at minute 7.5 then returned to chamber 24 hours later. Fear conditioning data showed that, following a stroke rats froze 16.48 +/- 2.75%, compared to the moderate intensity group where rats froze 63.57 +/- 10.72 % (S.E.M, n = 10, p < 0.01, one-way ANOVA, Bonferroni post-hoc). Mild and heavy exercise groups froze 43.3 +/- 10.75% and 38.26 +/- 10.53% respectively. In conclusion, focal cerebral ischemia impairs cognitive function, however moderate intensity physical exercise has the most beneficial impact on cognitive recovery compared to other exercise intensities.
Cardiac arrest is a leading cause of death in the United States and results in a large population with cognitive deficits. These deficits are due to transient global ischemia and the resulting cell ...death within the CA1 region of the hippocampus and associated brain regions. The administration of the specific protein kinase C epsilon activator drug, ψε-Receptor for Activated C Kinase (ψεRACK), protects neurons within the CA1 region; however, the mechanism of action has not been fully elucidated. In this study, it was determined that ψεRACK treatment increased brain derived neurotrophic factor (BDNF) protein expression, tropomyosin related kinase B (TrkB) phosphorylation, and the expression of the protein activity-regulated cytoskeleton-associated protein (arc). The neuroprotective effect of ψεRACK is dependent upon TrkB phosphorylation and arc expression. ψεRACK treatment led to electrophysiological changes that were dependent upon arc expression, including decreased mEPSC amplitude and increased latency until anoxic depolarization. Additionally, it was determined that a middle-aged model of cardiac arrest resulted in cell death and behavioral deficits. Furthermore, it was determined that administration of ψεRACK at a higher dosage can overcome age-dependent reduction of arc protein expression and is a therapeutic candidate in the population most affected by ischemic injury, the elderly.
Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit ...connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underlying pigment locus,
, by using experimental enclosures of mice on different soil colors. Next, we show how a mutation in
associated with survival causes lighter coat color through changes in its protein binding properties. Together, our findings demonstrate how a sequence variant alters phenotype and then reveal the ensuing ecological consequences that drive changes in population allele frequency, thereby illuminating the process of evolution by natural selection.
CT of fundoplication McDonnell, 3rd, C H; Baker, M E; Cohan, R H ...
Journal of computer assisted tomography,
09/1991, Volume:
15, Issue:
5
Journal Article
Peer reviewed
To determine the CT findings postfundoplication, we retrospectively compared CT in 22 postfundoplication patients with CT in 22 patients with unrepaired hiatal hernias and gastroesophageal (GE) ...junction abnormalities and 24 patients with gastric or esophageal carcinoma involving the GE junction. Seventeen of the 22 postfundoplication patients had undergone a Nissen procedure. Of the 22 patients, 11 had esophageal dilatation, 14 had GE junction masses, 4 had esophageal wall thickening, 7 had surgical clips, and none had hepatic metastases or upper abdominal lymphadenopathy. Statistically, on CT, postfundoplication patients are more likely to have a GE junction mass (p = 0.023) and least likely to have wall thickening (p = 0.021). Nonetheless, because the findings occur frequently in each group, they are not diagnostic in the individual patient. However, 11 of 12 post-Nissen masses had the unique finding of an oval or linear central fat density within the mass. This finding was absent in the other postfundoplication masses and in those patients with repaired hiatal hernia or tumor. We conclude that pseudomasses occur on CT postfundoplication and can be indistinguishable from hiatal hernias and GE junction neoplasms unless a central fat density is present.
This one-of-a-kind collection of chapters takes the reader on a tour to explore innovative practices from classrooms, schools, districts, communities, and faraway places in the world. Each of the ...chapters-organized under six headings-tells an authentic, compelling story of a pioneering and successful initiative that breaks the traditional mold of instructional delivery and time-honored school organization. Breaking the Mold of School Instruction and Organization guides readers through examples of education initiatives which go beyond traditional classroom restraints to achieve surprising success.
We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar ...gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.
We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate ...(Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.
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