The effect of shear on neurodegeneration

Abstract

Glaucoma, hydrocephalus and head injury were Micrographics. characterized by elevated intraocular or intracranial pressure leading to neurodegeneration. Mechaltislxw of these diseases/injuries were still not understood. An in vitro model of shear induced neurodegeneration was established in order to elucidate the mechanism of neurodegeneration in glaucomas hydrocephalus and head injury. The model consisted of a differentiated human neuroblastoma cell line, SH-SY5Y, which was exposed to shear stresses of various magnitudes and durations in a controlled environment. Application of shear to differentiated SH-SY5Y cells led to loss of viability. Further analysis showed that sheared cells had a higher percentage of fragmented DNA than the non-sheared cells. In addition lactate dehydrogenate released by the sheared cells did not dicer significantly from the non-sheared cells, indicating that the sheared cells maintained the integrity of their plasma membranes. These results demonstrated that sheared cells died via apostasis, the form of cell death observed in vivo during glaucoma and head injury. Differentiated SH-SY5Y cells exhibited a sustained increase in NO production throughout 24 hours following shear application. Furthermore, incubating cells in the presence of EGTA (a calcium chelator), cycloheximide (a protein synthesis inhibitor), pertussis toxin (a GVGO protein inhibitor),and GDPPS (a nonspecific G protein inhibitor) protected cells from shear induced loss of viability, These data demonstrated that NO 2+ into the cell new protein synthesis and G protein activation are production Ca entry , important in the mechanism of shear induced apostasis in SH-SY5Y cells.