thalidomide  (Novartis)

Journal: Brain, behavior, and immunity

Article Title: Microglia depletion improves hippocampal circuit function after mild traumatic brain injury in male mice

doi: 10.1016/j.bbi.2025.106178

Figure Lengend Snippet: Excitability shifts in hippocampal circuitry point to pre-synaptic dysfunction after injury which is restored by application of thalidomide. (A-F) Fiber volley and fEPSP slope, at simulation ranging from 50 to 500 μA with error ellipses indicating 95% confidence. – demonstrate presynaptic dysfunctions, as the relationship between the fiber volley and the fEPSP does not significantly change after injury in all three subregions of the hippocampus. In – these disruptions are restored to sham levels post-thalidomide application in both area CA1 and omDG. However, in imDG , the correlation between fiber volley and fEPSP in injured vs. sham animals is different as shown by the lack of change in fiber volley slope and decreased overlap of the ellipses. This suggests that network excitability may be restored through a combination of presynaptic and postsynaptic means (see for details on analysis).

Article Snippet: Thalidomide (5 μM, Tocris Bioscience), an immunosuppressant ( ; ; ) was bath-applied in some slices from sham and injured animals to determine the effects of TNF-α on neural circuits.

Techniques:

Journal: Brain, behavior, and immunity

Article Title: Microglia depletion improves hippocampal circuit function after mild traumatic brain injury in male mice

doi: 10.1016/j.bbi.2025.106178

Figure Lengend Snippet: Thalidomide restores excitability in hippocampal circuits at 7 dpi. (A) I/O curves of fEPSP slopes in area CA1 show no interaction effects; however, the significant increase in excitability in both injured and sham slices post 15-minute bath application of thalidomide suggest main effects of treatment; two-way ANOVA: F(1, 13) = 9.107, p < 0.0099. (B) Outer molecular layer Dentate Gyrus (omDG) show decreased excitability in injured slices after thalidomide application with no changes in sham slices; two-way ANOVA F(1, 117) = 18.23, p < 0.0001. (C) Inner molecular layer Dentate Gyrus (imDG) also revealed no changes in sham slices but an increase in excitability in injured animals post-thalidomide application; two-way ANOVA: F(1, 117) = 5.777, p = 0.0319. Data shown as mean ± SEM; Injured: N = 8; Sham: N = 7. Asterisks for multiple comparisons indicate ****p < 0.0001.

Article Snippet: Thalidomide (5 μM, Tocris Bioscience), an immunosuppressant ( ; ; ) was bath-applied in some slices from sham and injured animals to determine the effects of TNF-α on neural circuits.

Techniques:

Journal: Theranostics

Article Title: Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations

doi: 10.7150/thno.121154

Figure Lengend Snippet: Thalidomide induced PDGFB expression improves AVM formation. (A) WB for PDGFB and GAPDH in CTRL and SMAD4 siRNAs HUVECs grown in complete medium and subject to 12 Dynes/cm 2 FSS for 24 h treated with DMSO or thalidomide (100 μM). (B) Quantification of PDGFB protein levels normalized to GAPDH in the indicate conditions (n = 4 independent experiments/group). (C) Negative confocal images of IB4 stained of P6 retinas from Tx induced Smad4 iΔEC neonates treated with DMSO or thalidomide. Yellow arrowheads indicate AVMs. (D) Quantification of AVM number per P6 retina in DMSO and thalidomide treated Smad4 iΔEC neonates (n = 13 retinas from 7-8 mice/genotype). (E,G,I,K) High magnification confocal images of P6 retina vascular plexus from Tx induced Smad4 iΔEC DMSO or thalidomide treated neonates, labeled for PDGFRβ (red) and IB4 (blue) E ; for PECAM (white) (G) ; for GM130 (red), Erg1 (white) and IB4 (green) (I) and for KI67 (red) and IB4 (blue) (K) . (F, H, J, L) Quantification of % PDGFRΒ+ pericyte coverage per capillary area from images in E (n = 5 retinas from 3-5 mice/group) (F) ; of EC size (μm 2 ) from images in G (n = 30 (10 measurements per retina from 3 mice/group)) (H) ; of % of oriented ECs against the direction of flow in vascular plexus capillaries from images in I (n = 6 (2 images per retina from 3 mice/group)) (J) and quantification of KI67 + ECs per vascular area from images in K (L) (n = 6 (2 images per retina from 3 mice/group)). a, artery; v, vein. Scale Bars: 100 μm in panel A , 20 μm in panels E , G , I ; 50 μm in panel K . Statistical significance was determined using 2-way Anova with Tukey's multiple comparison test in B and t-test in D , F , H , J , L . Data are represented as mean ± SEM with adjusted p values. ns: non-significant, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: Phosphatidylinositol-4,5-Biphosphate 3-Kinase (PI3K) inhibitor: Pictilisib (Selleckchem, 20 nM), CDK4/6 inhibitor (Palbociclib, 2 μM), Thalidomide (Selleckchem, 100 μM), all diluted in DMSO, were added to cells subject to 12 dynes/cm2 FSS for 24 h. Corresponding volumes of DMSO were added to CTRL cells.

Techniques: Expressing, Staining, Labeling, Comparison