Increases in tumor necrosis factor-α following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampus

Yuki Murakami, Kuniaki Saito, Akira Hara, Yuyan Zhu, Kaori Sudo, Masayuki Niwa, Hidehiko Fujii, Hisayasu Wada, Hiroshi Ishiguro, Hideki Mori, Mitsuru Seishima

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59 Citations (Scopus)


The actions of tumor necrosis factor-α (TNF-α) produced by resident brain cells and bone marrow-derived cells in brain following a transient global ischemia were evaluated. In wild-type mice (C57BI/6J) following 20 min ischemia with bilateral common carotid artery occlusion (BCCAo), TNF-α mRNA expression levels in the hippocampus were significantly increased at 3 h and 36 h and exhibited a biphasic expression pattern. There were no hippocampal TNF-α mRNA expression levels at early time points in either wild-type mice bone marrow transplanted (BMT)-chimeric-TNF-α gene-deficient (T/W) or TNF-α gene-deficient mice BMT-TNF-α gene-deficient mice (T/T), although TNF-α mRNA levels were detectable in T/W BMT mice at 36 h. Histopathological findings showed no intergroup differences between wild-type and TNF-α gene-deficient mice at 4 and 7 days after transient ischemia. In addition, nuclear factor-κB (NF-κB) was activated within 12 h after global cerebral ischemia, but electrophoretic mobility shift assays (EMSA) showed no intergroup differences between wild type and TNF-α gene-deficient mice. In summary, early hippocampal TNF-α mRNA expression may not be related to bone marrow-derived cells, and secondary TNF-α expression as early as 36 h after ischemia probably resulted mainly from endogenous brain cells and possibly a few bone marrow-derived cells. Although we cannot exclude the possibility of the TNF-a contribution to the physiologic changes of hippocampus after transient global ischemia, these results indicate that TNF-α does not influence the morphological changes of the hippocampal neurons under our study condition.

Original languageEnglish
Pages (from-to)1616-1622
Number of pages7
JournalJournal of neurochemistry
Issue number6
Publication statusPublished - 06-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience


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