Indicators for acute hypoxia--an immunohistochemical investigation in cerebellar Purkinje-cells

Abstract

The Purkinje-cells (PCs) of the cerebellum are highly vulnerable to hypoxic/ischemic insult. Calbindin-D28k is a calcium-binding protein that is strongly expressed in PCs. Following hypoxia, a decrease in its concentration has been found in animal models before any morphological change of the PCs took place. Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are increasingly expressed in tissues that undergo durations of hypoxia, and also in brain tissues. We examine whether a change in expression of any of these factors, or a combination of alterations, is an indicator of acute hypoxia. We investigated the intensity of neuronal immunoreactivity of calbindin-D28k, HIF-1α and VEGF retrospectively in 141 samples of human cerebellar tissue obtained from autopsies performed at the Institute of Legal Medicine of Hanover Medical School in 2007 and 2008. Three groups were compared. The first group comprises individuals (n=48) who died due to acute hypoxia, such as drowning or asphyxia. The second is a control group comprising individuals who died due to heart failure (n=56), and the third group comprised individuals who died almost instantly of polytraumata (n=37). Our study finds a statistically significant decrease in the expression of calbindin-D28k (p<0.05) in PCs in the acute hypoxia group, relative to the control groups. No changes in the expression of HIF-1α or in the expression of VEGF were observed in any of the groups. Consequently HIF-1α and VEGF were not suitable indicators, whereas detection of a decreasing concentration of calbindin-D28k supports a diagnosis of acute hypoxia.