Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in the gerbil hippocampus: pharmacological approach.
1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus after ischemia. 2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min. 3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after ischemia. 4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient cerebral ischemia.
Himeda
Toshiki
T
Department of Drug Metabolism and Therapeutics, Graduate school and Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Tounai
Hiroko
H
Hayakawa
Natsumi
N
Araki
Tsutomu
T
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D025801:Ubiquitin / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D011804:Quinolines; D025801:Ubiquitin; D020932:Nerve Growth Factor; C108475:pitavastatin