Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia.
We investigated the effect of minocycline on neuronal damage in the hippocampus and striatum in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. Minocycline (90 mg/kg, i.p., qd) or saline was injected immediately after BCCAO and daily for the next two days (45 mg/kg, i.p., bid). In order to reduce the variability in ischemic neuronal damage, we applied selection criteria based on regional cerebral blood flow (rCBF), evaluated using laser Doppler flowmetry, and the plasticity of the posterior communicating artery (PcomA), evaluated using India ink solution. In animals with rCBF that was less than 15% of the baseline value and with a smaller PcomA, of diameter less than one-third that of the basilar artery, we consistently observed neuronal damage in the striatum and hippocampal subfields, including medial CA1, CA2, and CA4. When the effect of minocycline was assessed with cresyl violet staining, neuronal damage in the medial part of the CA1 subfield and the striatum was found to be significantly attenuated, although minocycline did not protect against neuronal damage in the remaining hippocampal subfields. Immunohistochemistry for NeuN, adenosine A1 receptor, and SCIP/Oct-6 confirmed the region-specific effect of minocycline in the hippocampus. In summary, our results suggest that minocycline protects neurons against global forebrain ischemia in a subregion-specific manner.
Cho
Kyung-Ok
KO
Department of Pharmacology, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, 137-701, Seoul, Republic of Korea.
Kim
Seul-Ki
SK
Cho
Young-Jin
YJ
Sung
Ki-Wug
KW
Kim
Seong Yun
SY
D000818:Animals; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply / Q000473:pathology
D018696:Neuroprotective Agents; D008911:Minocycline