Neural injury, in ischaemia, trauma or neurodegenerative disease, triggers wide-ranging inflammatory changes in neighbouring glia (astrocytes, microglia) and recruitment of leukocytes, particularly T-cells, which play an important role in the immune surveillance of the damaged neural tissue and in dealing with neural infection. Recent studies using cell cultures and transgenic animals have started to shed light on the identity of molecular factors that induce these inflammatory changes, particularly cytokines such as IL6, TNF-alpha and TGF beta 1 (Raivich et al. 1999; Makwana & Raivich, 2005). However, inflammation is also frequently associated with enhanced axonal damage and neuronal cell death. For example, recent epidemiological studies show strongly enhanced risk of cerebral palsy in the presence of maternal and/or fetal infection (Kendall & Peebles, 2005). Application of E. coli lipopolysaccharide (endotoxin), the standard bacterial inflammatory stimulus, strongly enhances the sensitivity to hypoxic/ischemic insults in the neonatal animal, particularly if the stimulus is applied some time before, with a maximum 12h preceding the insult (Kendall et al. 2005). Moreover, analysis of the cellular changes involved using cell surface activation markers showed that this enhanced sensitivity coincides with microglial activation, and is preceded by that of brain vessels, pointing to an endothelial → microglial → neuronal cellular cascade. Here, the availability of conditional mutants now allows us to address the cell type-specific and time dependent roles of cytokines such as TNF and TGFb1 and intracellular signals which include ras/MEK/ERK and JNK&Jun pathways as well as intracellular pH (Kendall et al. 2006), in mediating these detrimental inflammatory changes in the injured brain.