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1.
Figure 3

Figure 3. Percentage of mice that spent more time in the target quadrant than any other quadrant.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

For details, see text. Number of mice per experimental group: Control: n = 7; TBI: n = 8, Irradiation: n = 8, TBI/Irradiation: n = 8; DFMO control: n = 6; DFMO/TBI: n = 6; DFMO/Irradiation: 5; DFMO/TBI/Irradiation: n = 6.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
2.
Figure 7

Figure 7. Total number of BrdU/GFAP positive cells per mm2 in the dentate subgranular zone.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

Overall, there was no interaction between drug (DFMO, vehicle) and treatment (trauma, radiation, RCI); however, independently both DFMO (p<0.001) and injury type (p<0.0001) had significant effects on the numbers of newly born astrocytes in the dentate SGZ. Each treatment group consisted of 8–11 mice. Each bar represents a mean value and error bars are SEM.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
3.
Figure 8

Figure 8. Total number of BrdU/CD68 (activated microglia) positive cells per mm2 in the dentate subgranular zone.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

Overall, there was no interaction between drug (DFMO, vehicle) and treatment (trauma, radiation, RCI); however, independently both DFMO (p<0.019) and injury type (p<0.0001) had significant effects on the numbers of newly born microglia. Each treatment group consisted of 8–11 mice. Each bar represents a mean value and error bars are SEM.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
4.
Figure 2

Figure 2. Spatial memory retention in the probe trial following the first day of hidden platform training.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

*p<0.05 or smaller versus any other quadrant. For details about the overall effect of quadrant and posthoc tests in individual groups, see text. Number of mice per experimental group: Control: n = 7; TBI: n = 8, Irradiation: n = 8, TBI/Irradiation: n = 8; DFMO control: n = 6; DFMO/TBI: n = 6; DFMO/Irradiation: 5; DFMO/TBI/Irradiation: n = 6.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
5.
Figure 5

Figure 5. Total number of BrdU positive cells in the dentate subgranular zone.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

There was a significant interaction between drug treatment and injury. RCI animals treated with vehicle showed a significantly higher number of total BrdU compared to sham control animal (*p<0.05). In animals treated with DFMO there was no differences in the total number of BrdU positive cells among the different injury group. Each treatment group consisted of 8–11 mice. Each bar represents a mean value and error bars are SEM.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
6.
Figure 6

Figure 6. Total number of BrdU/NeuN positive neurons per mm2 in the dentate subgranular zone.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

Overall, there was no significant interaction between treatment and drug and no effect of the treatment alone or drug alone. In control mice treated with vehicle trauma alone induced no changes while radiation alone decreased the number of BrdU+/NeuN+ cells in the ipsilateral hemisphere. Animals from the RCI group showed an increase in the numbers of newly born neurons compared to radiation alone. Each treatment group consisted of 8–11 mice. Each bar represents a mean value and error bars are SEM.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
7.
Figure 4

Figure 4. Percentages of hippocampal granule cell expressing Arc protein 30 min after the last probe trail of the Morris water maze.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

Two-way ANOVA revealed a significant interaction between drug treatment (DFMO vs vehicle) and injury (trauma, radiation, RCI). Animals treated with vehicle after trauma or RCI showed a significant reduction in the percentage of neurons expressing Arc relative to sham treated animals (#p<0.009, * p<0.02). There was no difference in the percentage of neurons expressing Arc between the different injury groups in the DFMO treated animals. Each treatment group consisted of 8–11 mice. Each bar represents a mean value and error bars are SEM.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.
8.
Figure 1

Figure 1. Experimental time line.. From: The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries.

Two-month-old C57BL/6 mice received whole body irradiation (4 Gy) and immediately after (∼15 min) received either controlled cortical contusion injury or sham craniotomy. Two weeks after injury animals were injected daily for 5 days with BrdU (100 mg/kg). DFMO was made available in the drinking water immediately upon recovery from surgery and for a total of 42 days and was stopped two days before cognitive testing in the Morris water maze. Animals were euthanized 30 minute after the last probe trial.

Susanna Rosi, et al. PLoS One. 2012;7(1):e31094.

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