Bilateral, vascular and perivascular glial upregulation of heat shock protein-27 after repeated epileptic seizures.
Heat shock protein-27 (HSP-27) is an inducible stress response protein. It inhibits apoptotic cell death and is a reliable marker for oxidative stress. We studied the induction of HSP-27 in rat brains on days 1, 4 and 14 after repeated, pentylenetetrazole (PTZ)-induced seizures using immunohistochemisty. Saline treated control rats showed no induction of HSP-27. HSP-27 reactive astrocytes were rarely seen 1 or 4 days after PTZ injection. When present, single astrocytes were located in the cortex and/or the hippocampus. After 14 days PTZ treatment, a bilateral distribution of HSP-27 immunoreactive glia was present in piriform and entorhinal cortices and in the dentate gyrus of most brains. Rats with most intense HSP-27 upregulation showed HSP-27 in amygdala and thalamic nuclei. Astrocytes associated with blood vessels presented strongest HSP-27 staining, but did not show upregulation of gial fibrillary acidic protein and none responded with HSP-47 expression. Additionally, HSP-27 immunoreactivity increased in the endothelial cells of blood vessels in the affected brain regions, although no neuronal induction occurred. Contrastingly, a subconvulsive dose of the glutamine synthetase inhibitor L-methionine sulfoxime, which acts directly on astrocytes, resulted in a rapid, homogeneous astrocyte-specific HSP-27 upregulation within 24 h. Thus, repeated PTZ-induced seizure activity elicits a focal "heat shock" response in endothelial cells and astrocytes of selected cerebral regions indicating that expression of HSP-27 occurred in a seizure-dependent manner within the affected cerebral circuitries. Therefore, this PTZ-model of repeated seizure activity exhibited a cortical pattern of HSP-27 expression which is most comparable to that known from patients with epilepsy.
Bidmon
Hans-J
HJ
C. & O. Vogt Institute for Brain Research, Heinrich-Heine-University, Universitätsstr. 1, D-40225 Düsseldorf, Germany. hjb@hirn.uni-duesseldorf.de
Görg
Boris
B
Palomero-Gallagher
Nicola
N
Schliess
Freimut
F
Gorji
Ali
A
Speckmann
Erwin-J
EJ
Zilles
Karl
K
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004569:Electroencephalography; D042783:Endothelial Cells / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation
D003292:Convulsants; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase; D010433:Pentylenetetrazole