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Chronic stress and/or glucocorticoid administration produces atrophy of hippocampal neurons. However, evidence of the impact of glucocorticoids on glial cells, especially in both males and females, is limited. In the present study, we investigated the total percentage body weight, hippocampal volume and hippocampal astrocyte numbers following chronic corticosterone treatment in male and female Wistar rats. Males had greater left and right hippocampal volumes overall, but no effect on hippocampal volume was seen after corticosterone treatment. Total body weight was dose-dependently lower in both sexes, but the decrease was more prominent in male rats. Corticosterone treatment dose-dependently increased astrocyte numbers in the CA1 region, but not in the lateral and medial CA3 hippocampal regions. This increase was similar in both male and female rats. The astrogliosis observed following chronic corticosterone may have implications for extrasynaptic communication and neuron-glia interactions and is similar to changes in the astrocytic population observed in aged rats.
The extracellular matrix molecule complex stabilized by Bral1 at the nodes of Ranvier might play a role in neuronal conduction as this complex represents a reservoir and/or diffusion barrier for Na+ ions. We measured the apparent diffusion coeffi cient of water (ADCW) by diffusion-weighted MRI and the extracellular space (ECS) diffusion parameters volume fraction α (α = ECS volume/total tissue volume) and tortuosity λ (λ2 = free/apparent diffusion coeffi cient) by the real-time iontophoretic method. Measurements were done in the somatosensory cortex and along the mediolateral (x), rostrocaudal (y) and ventrodorsal (z) axes in the corpus callosum (CC) of Bral1 +/+ and -/- mice. In the cortex, we did not fi nd any signifi cant differences in the ECS diffusion parameters or ADCW values between Bral1 +/+ and -/- mice. In the CC, λ in Bral1 +/+ mice was signifi cantly higher along all three axes (λx = 1.41 ± 0.03; λy = 1.70 ± 0.02; λz = 1.72 ± 0.01; mean ± SEM) compared to -/- mice (λx = 1.32 ± 0.02; λy = 1.56 ± 0.01; λz = 1.58 ± 0.02); there were no signifi cant differences in α. These data were confi rmed by a lower ADCW in the CC of Bral1 +/+ than of -/- mice, along the x (1 158 ± 55 μm2 s-1 and 1 340 ± 25 μm2 s-1, respectively) and y axes (442 ± 19 μm2 s-1 and 521 ± 24 μm2 s-1, respectively). We conclude that the deletion of Bral1 results in a reduction of diffusion barriers at the nodes of Ranvier, which in turn facilitates diffusion in all directions in the myelinated white matter.
Currently, there is no effective strategy for the treatment of spinal cord injury (SCI). A combination of biomaterials and stem cell therapy seems to be a promising approach to increase regenerative potential after SCI. We evaluated the use of a cell-polymer construct based on a combination of the conditionally immortalized spinal progenitor cell line SPC-01_GFP3, derived from human fetal spinal cord tissue, with a serotonin-modified poly(2-hydroxyethyl methacrylate) hydrogel (pHEMA-5HT). We compared the effect of treatment with a pHEMA-5HT hydrogel seeded with SPC-01_GFP3 cells, treatment with a pHEMA-5HT only and no treatment on functional outcome and tissue reconstruction in hemisected rats. Prior to transplantation the cell-polymer construct displayed a high potential to support the growth, proliferation and differentiation of SPC-01 cells in vitro. One month after surgery, combined hydrogel-cell treatment reduced astrogliosis and tissue atrophy and increased axonal and blood vessel ingrowth into the implant; however, two months later only the ingrowth of blood vessels remained increased. SPC-01_GFP3 cells survived well in vivo and expressed advanced markers of neuronal differentiation. However, a majority of the transplanted cells migrated out of the lesion and only rarely remained in the hydrogel. No differences among the groups in motor or sensory recovery were observed. Despite the support of the hydrogel as a cell carrier in vitro, and good results in vivo one month postsurgery, there was only a small effect on long term recovery, mainly due to the limited ability of the hydrogels to support the in vivo growth and differentiation of cells within the implant. Further modifications will be necessary to achieve stable long term improvement in functional outcome.
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