Burn injury induces gelsolin expression and cleavage in the brain of mice.

Gelsolin is an actin filament-severing and capping protein, affecting cellular motility, adhesiveness and apoptosis. Whether it is expressed in the brain of burned mice has not yet been characterized. Mice were subjected to a 15% total body surface area scald injury. Neuropathology was examined by hematoxylin and eosin staining. Cerebral gelsolin mRNA, distribution and cleavage were demonstrated by quantitative polymerase chain reaction (QPCR), immunohistochemistry and Western blot, respectively. Cysteinyl aspartate-specific protease (caspase)-3-positive cells and activity were also measured. Burn injury could induce pathological alterations in the brain including leukocyte infiltration, necrosis, microabscess and gliosis. Compared with sham-injured mice, gelsolin mRNA was up-regulated at 8h post-burn (pb) in a transient manner in the cortex and striatum of burned mice, while it remained at higher levels in the hippocampus up to 72 hpb. Of interest, gelsolin was further cleaved into 42 and 48 kDa (kilo Dalton) fragments as illustrated in the hippocampus at 24 hpb, and was widely expressed in the brain by activated monocyte/macrophages, astrocytes and damaged neurons. In the meantime, caspase-3-positive cells were noted in the striatum of burned mice and its activity peaked at 24 hpb. To clarify inflammation-induced gelsolin expression and cleavage in the brain, rat pheochromocytoma cells were exposed to lipopolysaccharide to show increased gelsolin expression and caspase-3-dependent cleavage. The results suggest that burn-induced cerebral gelsolin expression would be involved in the activation of both the monocytes and astroglial cells, thereby playing a crucial role in the subsequent inflammation-induced neural apoptosis following burn injury.