Hypoxia-
ischemia induces an inflammatory response in the immature central nervous system that may be important for development of
brain injury. Recent data implicate that
chemoattractant cytokines,
chemokines, are involved in the recruitment of immune cells. The aim was to study alpha- and
beta-chemokines in relation to the temporal activation of inflammatory cells after
hypoxia-
ischemia in immature rats.
Hypoxia-
ischemia was induced in 7-day-old rats (left carotid artery occlusion + 7.7%
oxygen). The pups were decapitated at different times after the insult. Immunohistochemistry was used for evaluation of the inflammatory cell response and RT-PCR to analyze the
cytokine mRNA and
chemokine mRNA expression. A distinct
interleukin-1beta and
tumor necrosis factor-alpha cytokine expression was found 0-24 h after
hypoxia-
ischemia that was accompanied by induction of
alpha-chemokines (growth related gene and
macrophage inflammatory protein-2). In the next phase, the beta2-integrin expression was increased (12 h and onward) and neutrophils transiently invaded the vessels and tissue in the
infarct region. The
mRNA induction for the
beta-chemokines macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and
RANTES preceded the expression of markers for lymphocytes [cluster of differentiation (CD)4, CD8], microglia/macrophages (MHC I), and natural killer cells in the
infarct area. The activation of microglia/macrophages, CD4 lymphocytes, and astroglia persisted up to at least 42 d of postnatal age implicating a chronic component of immunoinflammatory activation. The expression of
mRNA for alpha- and
beta-chemokines preceded the appearance of immune cells suggesting that these molecules may have a role in the inflammatory response to insults in the immature central nervous system.