The injected dye was mostly located in the hippocampus

CA

The injected dye was mostly located in the hippocampus

CA1–3 region when injection time was longer TSA HDAC than 30 min (Supporting Information Fig. 4). In the water maze assessment, LPS injection resulted in neurologic deterioration at 3 days, with little improvement for up to 21 days. This deterioration of neurological function was restored by IL-13 injection (Fig. 6B and Supporting Information Fig. 5). Furthermore, injection of IL-13-neutralized antibody caused a similar neurologic outcome as that of the LPS group. Injection of IL-13 did not cause significant neurologic dysfunction compared with the PBS group. On the day of the worst neurologic dysfunction (3 days after stereotactic injection), the brain was harvested to assess the distribution of microglial/monocyte and neuronal survival (Fig. 6). LPS injection increased the deposition of CD11b with a reciprocal decrease in NeuN-positive

cells. Co-injection of LPS with IL-13 Sorafenib in vivo decreased the number of CD11b positive cells and further restored the number of NeuN positive cells. Ablation of IL-13 with IL-13 NA exerted the same effect as LPS injection. LPS injection increased the expression of C/EBP-α and C/EBP-β in CD11b positive cells, while the combination of LPS and IL-13 only caused the expression of C/EBP-α in CD11b positive cells. The combined effect of LPS and IL-13 in C/EBP-α and C/EBP-β was abolished by IL-13 NA. Hence, microglia/macrophage (CD11b positive cells) was activated by LPS injection and IL-13 further aggravated the microglia/macrophage cell loss. Attenuation of microglia/macrophage cells increased the number of neuronal cells and provided a more favorable neuro-behavioral response in animals. A previous study reported that IL-13-enhanced ER stress-related calpain activation plays an important role in the downregulation of PPAR-γ-regulated

HO-1 expression in activated microglia. The present study shows that IL-13 enhances COX-2/PGE2 expression through PLA2 and C/EBP-α regulation. More importantly, IL-13 simultaneously augments ER stress and calpain activity, and cleavage of C/EBP-β and PPAR-γ expression results in aggravation of activated microglia death. SSR128129E Finally, this study is the first to demonstrate that administration of IL-13 in activated microglia in an animal model enhances C/EBP-α expression, but abolished C/EBP-β expression, which diminishes neuronal cell loss and damage in regions associated with memory and the hippocampal CA3 region. The ER is a major component of the protein quality control system. Emerging evidence indicates a potent association between accumulation of protein aggregates and ER stress induction in various important neurodegenerative conditions. Previous reports have shown that calpain inhibitors have impressive neuroprotective effects in in vivo models of cerebral ischemia.

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