Ischemic tolerance in hippocampal CA1 neurons studied using contralateral controls.
We induced ischemic tolerance unilaterally in gerbil hippocampus using the contralateral hippocampus as control. Ischemia for 2 min of right common carotid occlusion was reversible but sufficient to cause heat-shock protein 70 production in CA1 neurons. This pretreatment given four days prior to occlusion of both common carotids for 5 min, but not at longer preceding intervals, induced tolerance in right CA1 neurons. Neuroprotection was still evident two months after the 5 min occlusion. Adenosine triphosphate content and immunoreactive microtubule associate protein 2 in the hippocampus showed that the 5 min ischemic insult was essentially equal in both hemispheres. Repetitive pretreatments at two day intervals caused almost complete protection of CA1 neurons against subsequent 5 min ischemia, while a single pretreatment showed 80% protection. However, the increase in heat-shock protein 70 with repeated pretreatments was not significantly more than with one pretreatment. We concluded that true ischemic tolerance was induced by ischemic stress itself, was long-lasting, was not due to mitigation of subsequent ischemia, and was augmented by repetition without further increase of heat-shock protein 70.
Kitagawa
K
K
First Department of Internal Medicine, Osaka University Medical School, Japan.
Matsumoto
M
M
Mabuchi
T
T
Yagita
Y
Y
Mandai
K
K
Matsushita
K
K
Hori
M
M
Yanagihara
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D000255:Adenosine Triphosphate