Intracellular and extracellular expression of the major inducible 70 kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord

Department of Anesthesiology, College of Medicine and Public Health, The Ohio State University, USA.
Experimental Neurology (Impact Factor: 4.62). 05/2008; 212(2):275-84. DOI: 10.1016/j.expneurol.2008.03.024
Source: PubMed

ABSTRACT Inflammatory responses exacerbate ischemia-reperfusion (IR) injury of spinal cord, although understanding of mediators is incomplete. The major inducible 70kDa heat shock protein (hsp70) is induced by ischemia and extracellular hsp70 (e-hsp70) can modulate inflammatory responses, but there is no published information regarding e-hsp70 levels in the cerebrospinal fluid (CSF) or serum as part of any neurological disease state save trauma. The present work addresses this deficiency by examining e-hsp70 in serum and CSF of dogs in an experimental model of spinal cord IR injury. IR injury of spinal cord caused hind limb paraplegia within 2-3 h that was correlated to lumbosacral poliomalacia with T cell infiltrates at 3 d post-ischemia. In this context, we showed a 5.2-fold elevation of e-hsp70 in CSF that was induced by ischemia and was sustained for the following 3 d observation interval. Plasma e-hsp70 levels were unaffected by IR injury, indicating e-hsp70 release from within the central nervous system. A putative source of this e-hsp70 was ependymal cells in the ischemic penumbra, based upon elevated i-hsp70 levels detected within these cells. Results warrant further investigation of e-hsp70's potential to modulate spinal cord IR injury.

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    • "A lack of correlation between serum and CSF ehsp70 concentrations supports local production and release of ehsp70 and not simply leakage from serum. Results support segregation of CSF and serum pools of ehsp70, a phenomenon that has been previously observed in humans and in experimental canine models (Oglesbee et al., 1999; Steensberg et al., 2006; Awad et al., 2008). Heat shock protein 70 release can occur passively from necrotic cells or by active secretory release (Basu et al., 2000; Bausero et al., 2005). "
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