Cytokine changes in the horizontal diagonal band of Broca in the septum after running and stroke: a correlation to glial activation

Abstract

The relationship between running, glial cell activation and pro-inflammatory cytokines was studied in the context of neuroprotection against ischemic stroke induced by middle cerebral artery occlusion (MCAO). This was investigated in four groups of rats, namely, (1) nonrunner, (2) runner after 12 weeks of treadmill running, (3) nonrunner with MCAO and (4) runner with MCAO. The horizontal diagonal band of Broca (HDB) in the septum was scrutinized for qualitative cum quantitative changes in the microglia and astrocytes. Reverse transcription-polymerase chain reaction and immunoblot work were carried out in the forebrain homogenate to determine, respectively, the gene and protein expression of several pro-inflammatory cytokines. Our results indicated that the runner exhibited less immunoreactivity and reduced numbers of glial cells within the HDB compared with the nonrunner. Interestingly, the mRNA and protein levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and interferon-gamma, were significantly downregulated in the runner. Our data also suggest albeit with some inconsistency that the runner/MCAO rats had benefited from running. These observations suggest that running can result in changes to the microenvironment, in which the microglia and astrocytes exist in a state of quiescence concomitant with a reduced expression of pro-inflammatory cytokines, that may lead to beneficial effects seen in ischemic stroke induced by MCAO.