Brain Spurt Case Study

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I. Key Points

• Evidence from animal studies supports a causal relationship between intravenous and inhaled anesthetic exposure and brain development, triggering increased apoptosis, with negative neurocognitive and behavioral outcomes.
• All these negative events take place during a high vulnerability period on brain development known as “brain spurt”.
• Normally, 70% of neurons will undergo apoptosis during brain development. Gamma aminobutyric acid (GABA) and glutamate receptor modulation may be involved in apoptotic pathway signaling. Anesthetic drugs exert their actions through these receptors, among many others, to produce loss of consciousness.
• Delaying non-elective surgical procedures might put children at risk of disease progression,
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Both NMDA and GABA receptors have been linked to impaired synaptogenesis and increased neuro-apoptosis in alcoholic fetal syndrome (5). Whether or not anesthetic modulation of these neurotransmitter pathways impairs synaptogenesis and/or neurodevelopment in early infancy is still a matter of debate and growing research. Translating results from animal models to clinical practice is challenging, as long as animal research procedures may not reflect the pediatric anesthetic practice (6, 7).

III. Human Brain Development.
Human brain development is a complex and tightly regulated process that starts early in the embryonic period and extends throughout the fetal and postnatal life (8). There is extensive genetic control over early brain development on the anatomic, cellular and molecular levels. Recent research has improved our understanding of the different factors that influence this process. Human brain development is also dynamic and adaptive in nature as well (9). As a result, the brain reaches 90% of its adult size by the age of five (1, 10).

A. Embryonic period (Conception – Week
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Later types of neural stem cells exhibit “fate restriction” and lose the ability to generate different cell lines (20).

• Synaptogenesis: Upon reaching the cortex, migrating neurons extend axons to establish connections with other neural cells. Axonal growth and synaptogenesis are tightly molecularly controlled events. Both are essential for the development of the major neural pathways (1). Brain spurt and pruning is followed by a systematic breakdown of up to 50% of the newly created synapsis throughout the prenatal and early postnatal life (2, 3). This process, along with apoptosis, ensures the normal development of the neural network.
• Myelination: Oligodendrocyte progenitor cells start to differentiate in the second trimester into oligodendrocytes, closely related to the neuronal axons. Myelin production from oligodendrocytes creates the myelin sheaths that increase axonal conductivity (21). Moreover, oligodendrocytes contribute to axon integrity and neuronal survival through the synthesis of neurotrophic factors (1).
C. Postnatal

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