Therapeutics for neonatal brain injury

University of California, San Francisco, United States
Pharmacology [?] Therapeutics (Impact Factor: 7.75). 10/2008; 120(1):43-53. DOI: 10.1016/j.pharmthera.2008.07.003

ABSTRACT Neonatal brain injury is an important cause of death and neurodevelopmental delay. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to both early and late phases of cell damage and death. Therapies targeting these different pathways have shown potential in protecting the brain from ongoing injury. More recent therapies, such as growth factors, have demonstrated an ability to increase cell proliferation and repair over longer periods of time. Even though hypothermia, which decreases cerebral metabolism and possibly affects other mechanisms, may show some benefit in particular cases, no widely effective therapeutic interventions for human neonates exist. In this review, we summarize recent findings in neuroprotection and neurogenesis for the immature brain, including combination therapy to optimize repair.

  • Source
    • "Presently, optimal management of H/I brain injury involves prompt resuscitation, careful supportive care, and treatment of seizures. Although hypothermia is a promising new therapy, and recent studies suggested that head or whole-body cooling administered within 6 hours of birth reduces the incidence of death or moderate/severe disability at 12 to 22 months [12], there is undeniable need for the identification of new therapeutic targets for the implementation of clinical trials to address treatment of H/I encephalopathy [13]. Accordingly, epidemiological and experimental data have allowed researchers to identify a number of potential targets for neuroprotective strategies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the evolution of neonatal hypoxic/ischemic is essential for novel neuroprotective approaches. We describe the neuropathology and glial/inflammatory response, from 3 hours to 100 days, after carotid occlusion and hypoxia (8% O(2), 55 minutes) to the C57/BL6 P7 mouse. Massive tissue injury and atrophy in the ipsilateral (IL) hippocampus, corpus callosum, and caudate-putamen are consistently shown. Astrogliosis peaks at 14 days, but glial scar is still evident at day 100. Microgliosis peaks at 3-7 days and decreases by day 14. Both glial responses start at 3 hours in the corpus callosum and hippocampal fissure, to progressively cover the degenerating CA field. Neutrophils increase in the ventricles and hippocampal vasculature, showing also parenchymal extravasation at 7 days. Remarkably, delayed milder atrophy is also seen in the contralateral (CL) hippocampus and corpus callosum, areas showing astrogliosis and microgliosis during the first 72 hours. This detailed and long-term cellular response characterization of the ipsilateral and contralateral hemisphere after H/I may help in the design of better therapeutic strategies.
    06/2012; 2012:781512. DOI:10.1155/2012/781512
  • Source
    • "Sixteen adult male rats were injected i.p, 117 days after perinatal asphyxia, with 17β estradiol (water soluble, E4389, Sigma, St. Louis, Mo; 250 µg/kg) or vehicle (0.9% saline solution). Previous studies have shown that doses of estradiol not very different from the one selected for this study, reduce gliosis in male rats after a penetrating brain injury or after immune challenge (Tapia-Gonzalez et al., 2008; Barreto et al., 2009). The injections were repeated daily for 3 days consecutively (up to 119 days after perinatal asphyxia). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The capacity of the ovarian hormone 17beta-estradiol to prevent neurodegeneration has been characterized in several animal models of brain and spinal cord pathology. However, the potential reparative activity of the hormone under chronic neurodegenerative conditions has received less attention. In this study we have assessed the effect of estradiol therapy in adulthood on chronic glial and neuronal alterations caused by perinatal asphyxia (PA) in rats. Four-month-old male Sprague-Dawley rats submitted to PA just after delivery, and their control littermates, were injected for 3 consecutive days with 17beta estradiol or vehicle. Animals subjected to PA and treated with vehicle showed an increased astrogliosis, focal swelling and fragmented appearance of MAP-2 immunoreactive dendrites, decreased MAP-2 immunoreactivity and decreased phosphorylation of high and medium molecular weight neurofilaments in the hippocampus, compared to control animals. Estradiol therapy reversed these alterations. These findings indicate that estradiol is able to reduce, in adult animals, chronic reactive astrogliosis and neuronal alterations caused by an early developmental neurodegenerative event, suggesting that the hormone might induce reparative actions in the Central Nervous System (CNS).
    Experimental Neurology 03/2010; 223(2):615-22. DOI:10.1016/j.expneurol.2010.02.010 · 4.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Further advances in microelectronics will require a shift from process technology to design technology, and from hardware to software. Political, societal, and environmental constraints may present a larger challenge in the next decade than the development of the technology.
    Solid State Circuits Conferene, 1980. ESSCIRC 80. 6th European; 01/1980
Show more