A new neurological focus in neonatal intensive care

Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, Box 0410, 513 Parnassus Avenue, S211, San Francisco, CA 94143-0410, USA.
Nature Reviews Neurology (Impact Factor: 15.36). 08/2011; 7(9):485-94. DOI: 10.1038/nrneurol.2011.119
Source: PubMed


Advances in the care of high-risk newborn babies have contributed to reduced mortality rates for premature and term births, but the surviving neonates often have increased neurological morbidity. Therapies aimed at reducing the neurological sequelae of birth asphyxia at term have brought hypothermia treatment into the realm of standard care. However, this therapy does not provide complete protection from neurological complications and a need to develop adjunctive therapies for improved neurological outcomes remains. In addition, the care of neurologically impaired neonates, regardless of their gestational age, clearly requires a focused approach to avoid further injury to the brain and to optimize the neurodevelopmental status of the newborn baby at discharge from hospital. This focused approach includes, but is not limited to, monitoring of the patient's brain with amplitude-integrated and continuous video EEG, prevention of infection, developmentally appropriate care, and family support. Provision of dedicated neurocritical care to newborn babies requires a collaborative effort between neonatologists and neurologists, training in neonatal neurology for nurses and future generations of care providers, and the recognition that common neonatal medical problems and intensive care have an effect on the developing brain.

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Available from: Hannah C Glass, Feb 20, 2015
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    • "The treatment considerations for hypothermia in addition to combining other therapies are based on the evolving pathophysiology of neonatal brain injury, discussed by Ferriero et al. (133, 134). Using a combination of therapies may be more beneficial to tackle the activated cell death pathways; moreover, detecting it early in at-risk newborns may help prevent or reduce the disabilities following neonatal brain injury (133, 134). "
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    • "Our results raise the important and worrying question whether resuscitation paradigms where normocapnic conditions established in a fast manner will, in fact, lead to the promotion of birth-asphyxia seizures. Graded restoration of normocapnia and/or drugs targeting the Na/H exchange in the blood–brain barrier offer an effective and straightforward means to functionally suppress seizures and ameliorate other neurological sequela after birth asphyxia (Rakhade and Jensen, 2009; Bonifacio et al., 2011), and can be readily used in conjunction with other treatment modalities, such as hypothermia (Johnston et al., 2011) and optimization of blood oxygenation levels (Saugstad, 2010). "
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    ABSTRACT: Birth asphyxia is often associated with a high seizure burden that is predictive of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old rat pups, we have recently shown that the seizure burden is linked to an increase in brain extracellular pH that consists of the recovery from the asphyxia-induced acidosis, and of a subsequent plateau level well above normal extracellular pH. In the present study, two-photon imaging of intracellular pH in neocortical neurons in vivo showed that pH changes also underwent a biphasic acid-alkaline response, resulting in an alkaline plateau level. The mean alkaline overshoot was strongly suppressed by a graded restoration of normocapnia after asphyxia. The parallel post-asphyxia increase in extra- and intracellular pH levels indicated a net loss of acid equivalents from brain tissue that was not attributable to a disruption of the blood-brain barrier, as demonstrated by a lack of increased sodium fluorescein extravasation into the brain, and by the electrophysiological characteristics of the blood-brain barrier. Indeed, electrode recordings of pH in the brain and trunk demonstrated a net efflux of acid equivalents from the brain across the blood-brain barrier, which was abolished by the Na/H exchange inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H exchange also suppressed the seizure activity associated with the brain-specific alkalosis. Our findings show that the post-asphyxia seizures are attributable to an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the blood-brain barrier and to consequent brain alkalosis. These results suggest targeting of blood-brain barrier-mediated pH regulation as a novel approach in the prevention and therapy of neonatal seizures.
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    • ", and ( ii ) Zeynalov and colleagues report that low doses of exogenous CO protect against transient or permanent focal ischemia in adult mice [ 23 , 24 ] . Perinatal HI can be partially predicted based on the presence of several risk factors : signals of distress during intrauterine life and hypoxic - ischemic insults at birth ( Bonifacio et al . 2011 ) . Also , preterm newborns represent a high - risk population for brain injury due to HI [ 44 ] . Therefore , preconditioning - based strategies can become potential therapies for perinatal HI , and CO is a promising candidate . Other preconditioning - based strategies have also been developed for perinatal cerebral ischemia . In pigle"
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