Chapter 8 - Perinatal brain damage in children: Neuroplasticity, early intervention, and molecular mechanisms of recovery

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Abstract

During the perinatal period, the nervous system is very vulnerable to insult. At this time, the brain undergoes fast and complex maturational processes such as synaptogenesis, arborization, and apoptosis, and the response to the insult is highly dependent on its exact timing. There is evidence that some of the neuroplastic mechanisms adopted by the young brain after damage are unavailable at a later stage of maturation. This applies, for example, to the reorganization of language, the sensorimotor system, or the visual system. Expanding our knowledge on these mechanisms could help the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization at a time of greatest potential brain plasticity.

Introduction

The perinatal period, as defined by the World Health Organization (1992), starts at 22 completed weeks of gestation (the time when birth weight is normally 500 g) and ends 7 completed days after birth. In this long period of time, the nervous system is vulnerable to insult, so that perinatal brain injury is still the major cause of developmental disability in children, accounting for at least 25% of all cases (Shevell et al., 2000). For this reason, the underlying mechanisms of perinatal damage have always raised great interest and represent a fundamental aspect of developmental neuroscience. In the past few years, many steps forward have been made in this field, with relevant impact on clinical practice both in terms of early diagnosis and treatment. In particular, an essential contribution has been provided by the novel noninvasive neuroimaging techniques, which were developed from the 1980s, first with ultrasonography, and subsequently with computed tomography and magnetic resonance imaging. These new methodologies, increasingly applied also in children, allow in vivo investigations of cerebral lesions, monitoring their evolution, and so providing further insight on the relation between lesion and function and on the different types of reorganization.

The contribution, provided by the different areas of neuroscience in the investigation of the fetus and the infant, has clarified that the damage to the central nervous system (CNS) results from a large number of mutually interacting pathophysiological mechanisms. It is indeed possible to schematically distinguish two main phases in the genesis of perinatal neurological damage: the delivery and the last phase of intrauterine life, which, in most cases, are involved in the pathogenesis of brain damage. The negative potential of preterm birth or a difficult and prolonged delivery is influenced, for example, by the underlying conditions of the fetus, for example, regular intrauterine growth or having experienced a transient or chronic event resulting in lesions during gestation. Reference can be made to the effect on the fetus, and therefore on the infant, resulting from a hypoxic and/or infective placental disorder, a physical trauma or psychic stress in the mother or the use of drugs or toxic substances during pregnancy (Volpe, 2008).

Section snippets

Perinatal brain damage and timing and mechanisms of the insult

A key point in perinatal neurological damage is the timing of the insult (i.e., the level of maturation of the brain at the moment of the insult). Due to the complexity of the events happening over the last trimester of gestation, the nervous system displays a different response to a damaging event at different gestational ages, leading to different clinical and neuropathological pictures. In the past 3 months of gestation, neuronal multiplication and migration have been largely completed but

Early neuroplasticity: Differential mechanisms in various functional systems

Mechanisms of cerebral plasticity are thought to be more powerful during early development. For example, children are faster than adults in learning a new language or in achieving complex skills such as playing a musical instrument. In a classic experiment on string players, the extent of the cortical representation of the left digits was found to be inversely correlated with the age at which the person had begun to play, indicating a larger amount of cerebral plasticity in subjects with

Taking advantage of early neuroplasticity: The concept of environmental enrichment

The high plasticity of the young brain supports the concept of early intervention as a “neuroprotective” strategy that stimulates brain development during this important phase (Bonnier, 2008). Several programs proposed for early intervention in infants at risk of developmental disability, such as the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) (Als et al., 1986) and infant massage therapy (Field, 2002) are based on the concept of enriching the environmental

Conclusions

Despite the enormous advances since the seminal works of Margaret Kennard in the first half of the twentieth century, our knowledge about the influence of timing on brain plasticity is still limited. There is increasing evidence supporting a better outcome in subjects with congenital brain damage, but our understanding of the possible underlying mechanisms is still largely based on nonhuman models. Some of the strategies adopted by the immature brain are unavailable at a later stage. There is,

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