Hypoxia-ischemia free radicals

Innovative methodologies for in vivo microdialysis in immature subjects have facilitated research in multiple areas. Clinically driven experimentation on neonatal anoxia, hypoxia, or ischemia indicates that perinatal manipulations of oxygen and blood flow result in acute and chronic disruptions of neurotransmission and transmitter turnover (Chen et al., 1997 Nakajima et al, 1999 Ogasawara et al., 1999). Recently, a role for toxic free radicals in brain damage induced by prenatal infection was also delineated by in vivo microdialysis in rat pups (Cambonie et al, 2000, 2004). More subtle neonatal manipulations, such as maternal separation or periodic neonatal isolation, coupled with subsequent in... 

The authors cited a combination of ischemia and exci-totoxicity due to cocaine exposure as the possible cause of the brain injury. Oxidative stress and free radicals associated with cerebral hypoxia contribute to cell damage and death. 

Free radical formation is an important contributor to cell death and brain injury in many neurological diseases. Shortly after brain damage by hypoxia-ischemia, hemorrhage, or trauma, excessive reactive oxygen species (ROS) production occurs, and at the same time, there is an impairment of antioxidant protective mechanisms, which leads to oxidative stress (Heo et al 2005). 

Stress stimuli come in a variety of forms, such as deprivation of trophic factors, ionizing radiation, free radicals (e.g., peroxynitrite), hypoxia, ischemia, heat shock, lipid second messengers (such as ceramide) (Singh et al., 1998), TNF-a, or Fas-ligand. In the brain, neurons are especially susceptible to stress stimuli these stimuli lead to activation of intracellular pathways that either promote apoptosis or defense-adaptation mechanisms. At least three such pathways have been well studied. These pathways lead to the activation of c-Jun N-terminal kinases (JNKs), p38 kinases. 

Blomgren K, Hagberg H (2006) Free radicals, mitochondria, and hypoxia-ischemia in the developing brain. Free Radic Biol Med 40 388-397... 

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