Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury. (16th May 2012)

• Record Type: Journal Article
• Authors: Chavez-Valdez, Raul; Martin, Lee J.; Northington, Frances J.
• Other Names: Li Jianrong Academic Editor.
• Is Part Of: Neurology research international. Volume 2012(2012)
• Publication Date: 2012-05-16
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8005
• DOI: 10.1155/2012/257563
• Languages: English
• ISSNs: 2090-1852

Abstract

Abstract : Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI) brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis "continuum" in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP)-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.