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

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.