Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model of global cerebral ischemia.
Heat shock protein 70 (Hsp70) is induced in cells by a variety of stress conditions, is known to be cytoprotective, and has been proposed to be neuroprotective during brain ischemia. A recently developed mouse model of 12-min global cerebral ischemia by bilateral common carotid artery occlusion with artificial ventilation and bilateral monitoring of regional cerebral blood flow by laser Doppler was applied. We examined the expression and possible neuroprotective role of the inducible form of Hsp70 in the mouse brain following global cerebral ischemia. Ischemia induced a marked expression of Hsp70 in the ischemia vulnerable CA1-CA3 region of the hippocampus. Intraischemic hypothermia (33 degrees C) prevented cell damage without noticeable expression of Hsp70. A transgenic mouse overexpressing Hsp70 was subjected to 12 min of global cerebral ischemia, and the brain damage was evaluated after 4 days. No neuroprotection of ischemia-induced brain damage in hippocampus, striatum, cortex or thalamus was found in Hsp70 transgenic animals compared with wild-type littermate mice. We suggest that overexpression of Hsp70 following cerebral ischemia is an indicator of cell stress. Also, constitutively overexpression of Hsp70 is insufficient to effectively influence cell death after global cerebral ischemia in the mouse.
Olsson
Tomas
T
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, 22184, Lund, Sweden. tomas.olsson@expbr.lu.se
Hansson
Oskar
O
Nylandsted
Jesper
J
Jäättelä
Marja
M
Smith
Maj-Lis
ML
Wieloch
Tadeusz
T
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents