White matter injury could be the main type of head injury in very pre-term infants. The O4 positive oligodendrocyte progenitors, generally pre myelinating oligodendrocytes in P2 rat brain, would be the main target cells of damage in the white matter of very premature infants. In this study, we showed that P2 rat pups had selective white matter damage on P11 after Ganetespib molecular weight mw LPS sensitized HI. White matter injury in the immature brain was associated with early and sustained JNK activation in the microglia, vascular endothelial cells and oligodendrocyte progenitors within 24 h postinsult, and also with up-regulation of microglia activation, TNF phrase, BBB loss, and endothelial cell and oligodendroglial apoptosis 24 h post insult. Pharmacological or genetic inhibition of JNK paid off microglia initial, TNF appearance, BBB injury and oligodendrocyte progenitor apoptosis, and secured against white matter damage after LPS sensitized HI. These studies suggest that JNK signaling is the shared pathway linking neuroinflammation, vascular endothelial Infectious causes of cancer cell injury and BBB breakdown, and apoptosis of oligodendroglial precursor cells in the white matter injury of the immature brain. Very pre-term infants experience infectious insults and various HI through the neo-natal period. Disease might predispose to, or act in concert with, HI in premature infants. Past studies show that increased systemic cytokines in premature infants with chorioamnionitis are associated with hemodynamic disruption resulting in cerebral HI, although co morbid chorioamnionitis and placental perfusion deficiency set preterm infants at higher risk of abnormal neurological results than either insult alone. Our previous research utilizing Bortezomib molecular weight the P2 rat pup model to simulate head injury in very pre-term infants demonstrated that selective white matter injury might be induced by the mix of LPS and HI instead of by LPS publicity or HI alone. We discovered that lowdose LPS upregulated JNK activation within the white matter without causing tissue injury. In comparison, LPS HI elicited early and prolonged activation of JNK and resulted in white matter damage. Studies examining the mechanisms of LPS sensitization show early upregulation of genes connected with stress induced inflammatory reactions in the immature brain several hours after LPS exposure, and the priming effect might lead to increased vulnerability of the immature brain to HI following LPS exposure. The important features of LPS sensitized HI white matter injury in the immature mind include, neuro-inflammation, manifested as activation of microglia and up-regulation of TNF, vascular endothelial cell injury and BBB breakdown, and apoptosis of O4 positive oligodendrocyte progenitors. Although past studies have demonstrated that LPS and/or HI induced anybody of the key features of injury in the neo-natal animal brain, not many studies have examined the three pathogenic mechanisms as an oligodendrovascular system in the white matter, specially in the immature P2 rat brain.