PRO-INFLAMMATORY CYTOKINES IN THE PATHOGENESIS OF BRAIN INJURIES FOLLOWING PERINATAL INFECTION AND ANOXIA

Objectives: Antenatal infection and anoxia are the main pathogenic processes triggering grey and white matter injuries in the brain of human neonates. We used our original rat model of neonatal brain lesions to study the role of pro-inflammatory cytokines in perinatal infectious and hypoxic-ischemic (H/I) aggressions of the brain.

Methods: Infectious effect was produced by administrating lipopolysaccharide (LPS) intraperitoneally (ip) to pregnant rats from embryonic day 17 (E17) to E20. H/I was induced at postnatal day 1 (P1) by ligature of the right common carotid artery followed by exposure to hypoxia (7% O2) for 3.5 hours. IL-1, IL-2 and TNF mRNA and protein expressions were studied by RT-PCR and western blot. Brain injuries were examined at P3 and P8.

Results: The extent of neuronal cell injury in the brain of rats exposed to postnatal H/I was significantly increased by antenatal exposure to LPS. Experimental aggressions resulted in IL-1beta, IL-2 and TNF-alpha mRNA and protein increases in the neonatal brain.

Conclusion: Our animal model provides an experimental tool to study the role of pro-inflammatory cytokines in the pathophysiology of perinatal human brain lesions and subsequent cerebral palsy.