الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Neurotransmission is the major target in the brain to transmit signals between different neuronal cells building up neuronal circuits. To achieve this target, neurons undergo a continuous developmental process of proliferation, differentiation, dendritic and axonal development, synaptogenesis and finally formation of chemical neurotransmitters and their storage in synaptic vesicles.
This developmental process occurs at a highest rate during perinatal period, infancy and early childhood during which, brain structures and function are vulnerable to injury from various stimuli which could be chemical, biological and physical leading to neuronal cell degeneration and neurocognitive impairment. This is called “Neurotoxicity”.
Anesthetic induced developmental neurotoxicity (AIDN) during early stages of brain development affects neurogenesis, neurite growth, synaptogenesis, glial cell maturation and alteration of neurotransmitter function in the young growing brains. AIDN occurs through different molecular mechanisms such as: NMDA/GABAA receptors, mitochondrial disturbances, neuroinflammatory pathway,
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dysregulation of intracellular Ca+2, brain derived neurotrophic factor (BDNF) and transduction of other signals.
Several studies on animals have suggested mounting evidence that exposure to general anesthetics causes neuronal cell degeneration and neurocognitive impairment in animals. Such findings raise the concern regarding general anesthetic practice in newborns, infants and pregnant mothers.
Several retrospective cohort studies have indicated that early exposure to general anesthesia/surgery may place pediatric patients at risk for later learning and behaviour impairment. Those children receiving anesthesia before 3 years of age are more likely to have learning and behaviour disorders compared with peers without anesthesia. It seems that exposure to anesthesia in early life more than once or for a prolonged period adversely affects long-term neurodevelopmental outcomes in children.
Different substances and methods are thought to protect against AIDN such as: Erythropoietin (EPO), brain preconditioning with anesthetics, nicotinamide, vitamin C, vitamin D3, α2 adrenoceptor agonist, lithium, Activity-Dependent Neuroprotective Protein (ADNP), acetyl-L-
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carnitine, melatonin, 17β-estradiol, EUK-134 and pramipexole.
In spite of approved AIDN in animals exposed to general anesthetics and possible association between early exposure in humans and neurocognitive impairment, there is no evidence of AIDN in humans till now. We are waiting for an evidence coming from two international multi center studies, the GAS study and the PANDA study in the coming few years.