Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE.

We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4 mg/kg), Sob (5 mg/kg) or Sob-AM2 (5 mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.

Radiographic signs of acetabular retroversion using a low-dose slot-scanning radiographic system (EOS®).

INTRODUCTION: Acetabular retroversion is assessed using pelvic X-ray. Cross-over-sign (COS), posterior-wall-sign (PWS) and ischial-spine-sign (ISS) are important radiographic signs of the condition. The pelvic area is sensitive to radiation and thus, possibilities to reduce dose should be considered. The purpose was to compare radiographic signs of acetabular retroversion on conventional pelvic anteroposterior (AP) X-rays with a low-dose slot-scanning system (EOS) in a sample of patients with retroversion of the acetabulum and to compare the radiation doses. METHODS: 34 participants with radiographic signs of acetabular retroversion in one or both hips on conventional pelvic X-ray were consecutively recruited. Pelvic EOS-images were acquired in each patient and COS, PWS, ISS, COS-ratio and PWS-ratio was assessed. Radiation dose comparison of X-ray vs. EOS was performed using Dose-Area Products. RESULTS: Retroversion was present in 57 out of 68 hips. The absolute agreement was 91%, 84% and 76% for COS, PWS and ISS, respectively. No statistically significant differences were present between COS-ratio and PWS-ratio in either modality and Bland-Altman limits of agreement were narrow. The mean radiation dose was 1053 mGy*cm2 in X-ray and 593 mGy*cm2 in EOS (p = 0.003). CONCLUSION: The results indicate that pelvic EOS provides diagnostic qualities similar to conventional X-ray using 44% less radiation when radiographic signs of acetabular retroversion are assessed.

Early exposure to Aroclor 1254 in vivo disrupts the functional synaptic development of newborn hippocampal granule cells.

Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus may provide a sensitive indicator of environmental stress. We examined the effects of Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls (PCBs), on the development and function of newly generated dentate granule cells. Early exposure to A1254 has been associated with learning impairment in children, suggesting potential impact on the development of hippocampus and/or cortical circuits. Oral A1254 (from the 6th day of gestation to postnatal day 21) produced the expected increase in PCB levels in brain at postnatal day 21, which persisted at lower levels into adulthood. A1254 did not affect the proliferation or survival of newborn neurons in immature animals nor did it cause overt changes in neuronal morphology. However, A1254 occluded the normal developmental increase in sEPSC frequency in the third post-mitotic week without altering the average sEPSC amplitude. Our results suggest that early exposure to PCBs can disrupt excitatory synaptic function during a period of active synaptogenesis, and thus could contribute to the cognitive effects noted in children exposed to PCBs.