Heat shock treatment protects osmotic stress-induced dysfunction of the blood-brain barrier through preservation of tight junction proteins.
The blood-brain barrier (BBB) is a specialized structure in the central nervous system (CNS), which participates in maintenance of a state of cerebrospinal fluid homeostasis. The endothelial cells of the cerebral capillaries and the tight junctions between them form the basis of the BBB. Research has shown that destruction of the BBB is associated with diseases of the CNS. However, there is little research on how the BBB might be protected. In this study, we used a high osmotic solution (1.6 M D-mannitol) to open the BBB of rats and Evans blue dye as a macromolecular marker. The effect of heat shock treatment was evaluated. The results show that increased synthesis of heat shock protein 72 (Hsp72) was induced in the heated group only. BBB permeability was significantly less in the heat shock-treated group after hyperosmotic shock. The major tight junction proteins, occludin and zonula occludens (ZO)-1, were significantly decreased after D-mannitol treatment in the nonheated group, whereas they were preserved in the heated group. The coimmunoprecipitation studies demonstrated that Hsp72 could be detected in the precipitates of brain extract interacting with anti-ZO-1 antibodies as well as those interacting with anti-occludin antibodies in the heated group. We conclude that the integrity of tight junctions could be maintained by previous heat shock treatment, which might be associated with the increased production of Hsp72.
Lu
Tzong-Shi
TS
Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan, Republic of China.
Chen
Hsiang-Wen
HW
Huang
Maw-Hsiung
MH
Wang
Shu-Jung
SJ
Yang
Rei-Cheng
RC
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D007150:Immunohistochemistry; D008353:Mannitol / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*
D004234:Diuretics, Osmotic; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D008353:Mannitol