NIH
Pub Med Central
Fernando F. Gonzalez, M.D.a and Donna M. Ferriero, M.D.ab
Synopsis
Neonatal brain injury is an important cause of death and disability, with pathways of oxidant stress, inflammation, and excitotoxicity that lead to damage that progresses over a long period of time. Therapies have classically targeted individual pathways during early phases of injury, but more recent therapies such as growth factors may also enhance cell proliferation, differentiation and migration over time. More recent evidence suggests combined therapy may optimize repair, decreasing cell injury while increasing newly born cells.
Causes of early brain injury include stroke, birth trauma, metabolic or genetic disorders, status epilepticus, and asphyxial events. Perinatal asphyxia presents as encephalopathy, or hypoxic ischemic encephalopathy, occurring in 3 to 5 in 1000 live births [1], while stroke studies conservatively estimate an incidence of 1 in 4000 live births [2]. It is classically thought that hypoxic-ischemic (HI) injury leads to periventricular white matter damage in premature infants, while term infants develop cortical/subcortical lesions [3], but more recent evidence suggests that this distinction in injury type may not be so clear [4]. While many suffering from perinatal brain injury die during early life, the majority of survivors exhibit neurological deficits that persist, such as cerebral palsy, mental retardation or epilepsy [5]. Aside from hypothermia, no established therapies exist, and treatment and care for the sequelae of early brain injury requires significant resources. Even after maximal care, there is often little improvement in an individual’s overall abilities, with long-term effects on the family, health care system, and society [6].
Neuroprotection in the Newborn Infant
a Department of Pediatrics; University of California, San Francisco (FFG, DMF)
b Department of Neurology; University of California, San Francisco (DMF)
Author contact information: Donna M. Ferriero, M.D. Neonatal Brain Disorders Laboratory University of California, San Francisco 521 Parnassus Ave. C215 Box 0663 San Francisco, CA 94143 Phone: (415) 502-5820 Fax: (415) 502-5821 ; Email: ferrierod@neuropeds.ucsf.edu
Fernando F. Gonzalez, M.D. Neonatal Brain Disorders Laboratory University of California, San Francisco 521 Parnassus Ave. C215 Box 0663 San Francisco, CA 94143 Phone: (415) 502-8932 Fax: (415) 514-0235 gonzalezf@peds.ucsf.edu
The publisher’s final edited version of this article is available at Clin Perinatol
Synopsis
Neonatal brain injury is an important cause of death and disability, with pathways of oxidant stress, inflammation, and excitotoxicity that lead to damage that progresses over a long period of time. Therapies have classically targeted individual pathways during early phases of injury, but more recent therapies such as growth factors may also enhance cell proliferation, differentiation and migration over time. More recent evidence suggests combined therapy may optimize repair, decreasing cell injury while increasing newly born cells.
Keywords: neonatal stroke, hypoxia, ischemia, neuroprotection, neurogenesis
Causes of early brain injury include stroke, birth trauma, metabolic or genetic disorders, status epilepticus, and asphyxial events. Perinatal asphyxia presents as encephalopathy, or hypoxic ischemic encephalopathy, occurring in 3 to 5 in 1000 live births [1], while stroke studies conservatively estimate an incidence of 1 in 4000 live births [2]. It is classically thought that hypoxic-ischemic (HI) injury leads to periventricular white matter damage in premature infants, while term infants develop cortical/subcortical lesions [3], but more recent evidence suggests that this distinction in injury type may not be so clear [4]. While many suffering from perinatal brain injury die during early life, the majority of survivors exhibit neurological deficits that persist, such as cerebral palsy, mental retardation or epilepsy [5]. Aside from hypothermia, no established therapies exist, and treatment and care for the sequelae of early brain injury requires significant resources. Even after maximal care, there is often little improvement in an individual’s overall abilities, with long-term effects on the family, health care system, and society [6].
A search for therapies that can prevent injury progression or enhance repair of the immature brain continues, with the goal of improving long-term motor and cognitive outcomes. Because the neonatal and adult brain do not respond to insults in the same manner, secondary to differences in gene regulation during hypoxia and altered susceptibility to oxidative stress and excitotoxicity, alternate therapies must be sought [7]. Damage occurs via multiple pathways, and repair occurs over a period of days to weeks, if not months [8]. While some therapies that manipulate injury pathways show promise, not all neonates will benefit from treatment. Damage may be so severe or prolonged that repair may not be possible, or survivors may be particularly devastated [9].
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