Intracellular and extracellular expression of the major inducible 70 kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord
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). "
ABSTRACT: The role of extracellular 70 kDa heat shock protein 70 (ehsp70) in central nervous system inflammation is vastly understudied, despite evidence supporting the ability to drive a pro-inflammatory state. We investigated the presence of ehsp70 in cerebrospinal fluid (CSF) and serum of dogs with Steroid Responsive Meningitis-Arteritis (SRMA), with the hypothesis that an ehsp70 response would occur, and might play a role in the pathogenesis of this disease. Samples from 30 dogs acutely affected with SRMA, and 30 dogs treated with corticosteroids and currently in clinical remission from SRMA were compared with normal dogs. Serum and CSF concentrations of ehsp70 were quantified using an enzyme-linked immunosorbent assay. An ehsp70 response occurred in the CSF of dogs with SRMA and this response was attenuated by corticosteroid treatment. There was no correlation between serum and CSF concentrations of ehsp70, supporting local production and release of ehsp70 and not simply leakage from serum. Dogs with SRMA thus represent a powerful spontaneous model by which to study the role of ehsp70 in CNS inflammation.Veterinary Immunology and Immunopathology 11/2011; 145(1-2):129-33. DOI:10.1016/j.vetimm.2011.10.021 · 1.75 Impact Factor
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ABSTRACT: We have performed neutron scattering experiments to investigate the static magnetic structure and the magnetic critical scattering in the three-dimensional percolating Heisenberg antiferromagnet, RbMn0.31Mg0.69F3, whose magnetic concentration is just at the percolation concentration for a cubic lattice, cP=0.312. Magnetic scattering was observed around the superlattice point, (12,12,12). We determined the Néel temperature of this system to be TN=4.0±0.5K, and found that the critical scattering above TN is similar to that observed in the homogeneous system. At T=1.6K well below TN, the scattering function is described by a sum of the critical scattering and elastic scattering components, and we demonstrated that the q-variation of the intensity of the elastic scattering component can be described using the fractal dimension.Physica B Condensed Matter 11/2006; 385:441-443. DOI:10.1016/j.physb.2006.05.146 · 1.28 Impact Factor
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ABSTRACT: Heat shock proteins (HSPs) are normal intracellular proteins that are produced in greater amounts when cells are subjected to stress or injury. These proteins have been shown to play a key role in the modulation of the secondary injury that occurs after the initial spinal cord injury (SCI). Heat shock proteins normally act as molecular chaperones and are called protein guardians because they act to repair partially damaged proteins. Normally intracellular, HSPs can also be liberated into the systemic circulation to act as important inflammatory mediators. In the setting of SCI, HSP induction has been shown to be beneficial. These proteins are liberated primarily by acutely stressed microglial, endothelial, and ependymal cells. Heat shock proteins have also been shown to assist in the protection of motor neurons and to prevent chronic inflammation after SCI. In animal models, several experimental drugs have shown neuroprotective effects in the spinal cord and appear to function by modulating HSPs.Neurosurgical FOCUS 02/2008; 25(5):E4. DOI:10.3171/FOC.2008.25.11.E4 · 2.14 Impact Factor