Display Settings:

Items per page
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Results: 7

1.
Figure 3

Figure 3. EphA4 immunostaining is decreased adjacent to injury site in ephrin-A5-Fc treated mice.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

Immunohistochemical analysis of (A,B) GFAP, (C–F) EphA4 and (G,H) CSPG expression at 2 weeks after spinal cord hemisection and 2 weeks of ephrin-A5-Fc treatment indicated that there was robust GFAP staining in both treated and control mice (A,B). However, in treated mice ipsilateral astrocytes adjacent to the injury site had markedly decreased EphA4 staining (C–F). There was also moderately decreased CSPG staining adjacent to the injury site of treated mice (G,H). Arrows indicate lesion site. Scale bars in A–D, G,H, 100 µm; E,F, 50 µm.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
2.
Figure 1

Figure 1. Unclustered ephrin-A5-Fc and EphA4-Fc promote neurite outgrowth.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

(A) Immunoprecipitation (IP) of phosphotyrosine containing proteins using anti-pY100 antibody followed by immunoblot (IB) for EphA4 showed that unclustered ephrin-A5-Fc (uncl-A5) inhibits basal and IFNγ-induced EphA4 receptor phosphorylation in cultured astrocytes, whereas clustered ephrin-A5-Fc (cl-A5) upregulates EphA4 receptor phosphorylation. (B–C) Inhibition of neurite outgrowth on astrocytes was blocked in a dose-dependent manner by addition of unclustered EphA4-Fc; 10 µg/ml of EphA4-Fc and ephrin-A5-Fc were used in (C). Results in B show mean±SEM, ***p<0.001, using one-way ANOVA with Tukey's multiple comparison test, from n≥100 neurons per condition, representative of n = 3 experiments. Scale bar in C, 100 µm.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
3.
Figure 2

Figure 2. Unclustered ephrin-A5-Fc and EphA4-Fc partially reduce astrocytic gliosis.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

(A–C) Immunohistochemical analysis of GFAP expression 4 days after spinal cord hemisection and following 3 days administration of Fc fusion protein indicated that, (A) compared to PBS treatment (n = 6), ephrin-A5-Fc (n = 3) and EphA4-Fc (n = 3) treatment decreased astrocytic gliosis. There were significant decreases in the number of astrocytes (B) and GFAP density at the lesion site was reduced following ephrin-A5-Fc or EphA4-Fc treatment (C). Results in B and C show mean±SEM, **p<0.01, ***p<0.001, using one-way ANOVA with Tukey's multiple comparison test. Scale bar in A, 100 µm.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
4.
Figure 7

Figure 7. Prolonged treatment with EphA4-Fc and extended recovery.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

(A, B) To determine whether extending treatment length to 4 weeks promoted greater functional improvement EphA4-Fc was administered for 2 weeks or 4 weeks, after which (A) grasp score and (B) grid climbing accuracy were assessed at 6 weeks post-injury. Both the 2-week and 4-week treatments improved functional outcomes compared to controls, but were not significantly different to each other. (C, D). To determine whether extending the recovery period for longer than 6 weeks would allow further functional improvement, animals were treated with EphA4-Fc for 2 weeks after injury and assessed at 8, 12 and 24 weeks. Analysis of (C) grasp score and (D) grid climbing accuracy showed that no further improvements were observed after 8 weeks in control or treated mice. (mean±SEM, *p<0.05, **p<0.01).

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
5.
Figure 5

Figure 5. Axonal regeneration in ephrin-A5-Fc- and EphA4-Fc-treated spinal cords 6 weeks after injury.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

A montage of confocal images, 6 weeks after injury, from representative sections anterogradely traced with Fluoro-ruby showing that (A) PBS-treated mice had few labeled axons rostral to the lesion site. (B) One week of EphA4-Fc treatment increased the number of axons rostral to the lesion site but did not promote regeneration through it. A 2-week treatment with ephrin-A5-Fc (C) or EphA4-Fc (D) was sufficient to promote regeneration through and caudal to the lesion site. Scale bars for A–D, 50 µm. Arrows point to center of lesion site. (E) Axonal regrowth was determined by semi-quantitative analysis of labeled axons rostral and caudal to the lesion site after ephrin-A5-Fc (A5) or EphA4-Fc (A4) treatment for 1 week (1 W) or 2 weeks (2 W): ordinal scale 0 = no axons; 1 = fewer than 10 axons; 2 = 10–50 axons; 3 = more than 50 axons per section (from n≥5 sections per spinal cord). *p<0.05, ***p<0.001 compared to PBS control, using one-way ANOVA with Tukey's multiple comparison test.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
6.
Figure 4

Figure 4. Axonal regrowth towards the lesion site in ephrin-A5-Fc-treated spinal cords 2 weeks after injury.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

A montage of confocal images 2 weeks after injury from representative sections anterogradely traced with Fluoro-ruby showing that (A) PBS-treated mice had few labeled axons rostral to the lesion site and that (B) one week of ephrin-A5-Fc treatment increased the number of axons proximal to the lesion site. Axons in the ephrin-A5-Fc-treated mice had robust growth cones. Boxes show enlarged regions in a′ and b′. Scale bars for A, B, A′, B′, 50 µm. Dotted lines in A, B indicate the border of the lesion site and the right hand side of panels is caudal to the lesion site (C) Axonal regrowth was determined by semi-quantitative analysis of axons 100 µm or 750 µm rostral to the lesion site after ephrin-A5-Fc (A5) treatment for 1 week (1 W) or 2 weeks (2 W): ordinal scale 0 = no axons; 1 = fewer than 10 axons; 2 = 10–50 axons; 3 = more than 50 axons per section (from n≥5 sections per spinal cord). *p<0.05, **p<0.01, ***p<0.001 compared to the PBS-treated control, using one-way ANOVA with Tukey's multiple comparison test. (D) Two weeks treatment with ephrin-A5-Fc promoted substantial axonal regeneration into the lesion site; box enlarged in D′. Scale bars D, D′, 50 µm. (E) Regrowth of labeled corticospinal tract axons towards the lesion site at 2 weeks, after 2 weeks EphA4-Fc treatment, with distance from center of injury site; *p<0.05. (F) Representative images of labeled corticospinal tract axons 2 weeks after injury, and a 2-week treatment protocol, showing distance to the center of the injury site.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.
7.
Figure 6

Figure 6. Ephrin-A5-Fc- or EphA4-Fc-treated mice show significant functional recovery 5 weeks after spinal cord injury.. From: EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice.

(A) Walking and climbing on a grid were significantly improved following 2 weeks treatment with ephrin-A5-Fc (A5-2W) or EphA4-Fc (A4-2W). One week of ephrin-A5-Fc (A5-1W) treatment resulted in significant improvement in grid walking but not in climbing as assessed by ANOVA, although it was significant by t-test (mean±SEM, *p<0.05, ***p<0.001 using one-way ANOVA with Tukey's comparison analysis; #p<0.05 using t-test). (B) The mBBB score was measured up to 5 weeks after spinal cord injury (SCI) in PBS- (n = 7) and EphA4-Fc- (A4-Fc) (n = 6) treated mice. Results show mean±SEM (***p<0.001 comparing treatment groups at the indicated time point using one-way ANOVA with Tukey's multiple comparison test). Kinematics of the left hind limb were analyzed from videotapes of locomotion of mice on the treadmill with reflective markers on the iliac crest, hip joint, knee joint and ankle joints. (C–F) Stick figures of the angles between each joint were used to depict one complete step cycle, with the beginning of the swing phase marked with an arrow for the push off point (PO) of the left hind limb and the pattern obtained for a normal intact mouse at a treadmill speed of 12 m/min (C). Panels (D–F) show a representative pattern for one mouse from each of the PBS (n = 7), ephrin-A5-Fc (A5-Fc) (n = 2) and EphA4-Fc (A4-Fc) (n = 6) groups of mice 5 weeks after spinal cord injury, at a treadmill speed of 12 m/min. Treatment over 2 weeks with ephrin-A5-Fc and EphA4-Fc resulted in approximation of the movement pattern seen in intact animals, including a phase of lifting the paw off the surface. (G–I) Average kinematic profile combined from profiles of EphA4-Fc-treated mice (n = 6), of joint angle changes over one complete step cycle of the left hip (G), knee (H) and ankle joints (I) 5 weeks after spinal cord injury in PBS- and EphA4-Fc-treated mice compared to the intact mouse pattern. The point of push off (PO) and the beginning of the swing phase is indicated by a black vertical line through the graph. Results are expressed as mean±SD.

Yona Goldshmit, et al. PLoS One. 2011;6(9):e24636.

Display Settings:

Items per page

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk