Since microglia, vascular endothelial cells and oligodendrocytes may closely interact with each other in the white matter, there may be a common order Everolimus signaling mechanism connecting neuro-inflammation, BBB disruption and oligodendroglial progenitor cell apoptosis in the white matter damage of the immature brain. c Jun N terminal kinases are critical stressresponsive kinases that are triggered by various kinds of insults, including ischemia. JNK activation precedes cell death by inflammation and apoptosis in many cell types. Activation of JNK signaling leads not only to cell death via intrinsic/extrinsic apoptotic pathways, but in addition to pro inflammatory cytokine production. In vitro studies show that JNK signaling is the predominant process for cytokine production from LPSstimulated or hypoxia exposed microglia. JNK signaling also plays an important role in subarachnoid hemorrhage associated BBB disruption, and stressinduced apoptosis of cerebral endothelial cells and oligodendrocyte progenitors. In vivo studies demonstrated early and sustained JNK service after cerebral ischemia. Our previous Organism study in P7 rat pups showed that neonatal chubby increased HI induced microglial activation, neuronal apoptosis and BBB damage in the cerebral cortex, and irritated cortical damage through JNK hyperactivation. But, it remains unclear whether JNK activation could be the common pathogenic mechanism in the oligodendrovascular device leading to white matter injury in the immature brain of P2 rat pups. Utilizing an established model of LPS sensitized HI white matter injury in P2 rat pups, we hypothesized that JNK signaling is the shared pathway linking neuroinflammation, microvascular endothelial cell injury and BBB breakdown, Ibrutinib clinical trial and apoptosis of oligodendroglial precursor cells in the white matter injury of the immature brain. The animal study was accepted by the Animal Care Committee at National Cheng Kung University. Dawley rat pups were stored under standard condition using a 12/12 h light/dark cycle. We first shot P2 rat pups intraperitoneally with 0. 05 mg/kg LPS or pyrogen free normal saline. Neuropathological tests conducted on P11 showed that, in contrast to the NS treated group, the LPS treated pups had no significant injury in the cortex and white matter. The LPS addressed dogs also showed no proof of microglial activation and BBB breakdown within the white matter. These studies suggested low-dose LPS did not cause damage in the cortex or upregulate neuroinflammation and BBB disruption in the white matter of P2 rat pups. As described previously, we then shot P2 dogs with LPS or NS 3 h before HI. Pups were randomly assigned to three different groups, control, NS HI, and LPS HI. To avoid LPSinduced body temperature changes, the rat pups were returned to their dams after injection, and housed within an incubator to maintain body temperature at 33 to 34 C before HI.