title: Cytokines and perinatal brain injury.
abstract: A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor 48109, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Silverstein
authors.forename: J D
authors.initials: JD
authors.lastname: Barks
authors.forename: P
authors.initials: P
authors.lastname: Hagan
authors.forename: X H
authors.initials: XH
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Ivacko
authors.forename: J
authors.initials: J
authors.lastname: Szaflarski
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D005315:Fetal Diseases / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000473:pathology*; D007375:Interleukin-1 / Q000502:physiology; D010972:Platelet Activating Factor / Q000502:physiology; D051381:Rats
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D010972:Platelet Activating Factor