Gary M Fiskum

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury.

Courtney L Robertson; Susanna Scafidi; Mary C McKenna; Gary Fiskum (Profiled Authors: Gary M Fiskum; Mary C McKenna)

Department of Pediatrics, University of Maryland School of Medicine, Baltimore, 21201, USA.
Experimental neurology 2009;218(2):371-80.

There are several forms of acute pediatric brain injury, including neonatal asphyxia, pediatric cardiac arrest with global ischemia, and head trauma, that result in devastating, lifelong neurologic impairment. The only clinical intervention that appears neuroprotective is hypothermia initiated soon after the initial injury. Evidence indicates that oxidative stress, mitochondrial dysfunction, and impaired cerebral energy metabolism contribute to the brain cell death that is responsible for much of the poor neurologic outcome from these events. Recent results obtained from both in vitro and animal models of neuronal death in the immature brain point toward several molecular mechanisms that are either induced or promoted by oxidative modification of macromolecules, including consumption of cytosolic and mitochondrial NAD(+) by poly-ADP ribose polymerase, opening of the mitochondrial inner membrane permeability transition pore, and inactivation of key, rate-limiting metabolic enzymes, e.g., the pyruvate dehydrogenase complex. In addition, the relative abundance of pro-apoptotic proteins in immature brains and neurons, and particularly within their mitochondria, predisposes these cells to the intrinsic, mitochondrial pathway of apoptosis, mediated by Bax- or Bak-triggered release of proteins into the cytosol through the mitochondrial outer membrane. Based on these pathways of cell dysfunction and death, several approaches toward neuroprotection are being investigated that show promise toward clinical translation. These strategies include minimizing oxidative stress by avoiding unnecessary hyperoxia, promoting aerobic energy metabolism by repletion of NAD(+) and by providing alternative oxidative fuels, e.g., ketone bodies, directly interfering with apoptotic pathways at the mitochondrial level, and pharmacologic induction of antioxidant and anti-inflammatory gene expression.

3 Originating Grant

• 1.

  Zielke, H Ronald

  Metabolic & Developmental Aspects of Mental Retardation

  1 May 1997 - 31 January 2009

  NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

• 2.

  MCKENNA, MARY C

  Metabolic &Developmental Aspects of Intellectual Disability

  1 May 1997 - 31 January 2014

  EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT

• 3.

  Fiskum, Gary

  Molecular Mechanisms of Ischemia Reperfusion Brain Injury

  1 May 1995 - 31 December 2008

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.