Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia

Kyung Ok Cho, Seul Ki Kim, Young Jin Cho, Ki Wug Sung, Seong Yun Kim

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2030-2035
Number of pages6
JournalLife Sciences
Volume80
Issue number22
DOIs
StatePublished - May 8 2007

Fingerprint

Minocycline
Neuroprotective Agents
Prosencephalon
Ischemia
Cerebrovascular Circulation
Regional Blood Flow
Hippocampus
Blood
Arteries
Adenosine A1 Receptors
Laser-Doppler Flowmetry
Basilar Artery
Common Carotid Artery
Halothane
Inbred C57BL Mouse
Patient Selection
Neurons
Plasticity
Animals
Immunohistochemistry

Keywords

  • Global forebrain ischemia
  • Hippocampus
  • Minocycline
  • Mouse
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia. / Cho, Kyung Ok; Kim, Seul Ki; Cho, Young Jin; Sung, Ki Wug; Kim, Seong Yun.

In: Life Sciences, Vol. 80, No. 22, 08.05.2007, p. 2030-2035.

Research output: Contribution to journalArticle

Cho, Kyung Ok ; Kim, Seul Ki ; Cho, Young Jin ; Sung, Ki Wug ; Kim, Seong Yun. / Regional differences in the neuroprotective effect of minocycline in a mouse model of global forebrain ischemia. In: Life Sciences. 2007 ; Vol. 80, No. 22. pp. 2030-2035.
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AB - 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.

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