Therapeutic Values of General Anesthetics: From Developmental Neurotoxicity to Neurotherapeutic Agents

The development of the central nervous system is characterized by precisely orchestrated, dynamic processes that commence at the embryonic stage and continue throughout postnatal life. Maintaining the balance between excitation/inhibition (E/I) in cortical neuronal circuits is crucial for normal brain function. General anesthetics (GAs) powerfully modulate neuronal activity by enhancing inhibition and/or inhibiting excitability, resulting in temporary loss of consciousness. Therefore, these agents can also induce aberrant neuroplasticity contributing to neurological dysfunction and abnormal behavioural phenotypes, particularly in the developing brain. While this impaired plasticity poses a risk, it also creates an opportunity to treat diseases characterised by abnormal neuroplasticity as core pathologies, such as neuropsychiatric disorders (NPDs). Over recent decades, intense investigations have revealed the neuroprotective and psychotherapeutic potential of GAs in treating neurological injuries and NPDs. Although promising, significant challenges remain, including optimizing dosages, administration duration, and intervals for non-anesthetic uses while minimizing adverse effects. Additionally, the molecular mechanisms underlying the dual roles of GAs - as neurotoxic agents and neurotherapeutic tools - require further elucidation. This review explores developmental neuroplasticity during critical periods, the mechanisms of GAs' action on neural circuits, and the current understanding of their neurotoxic and neuroprotective effects based on alterations in neuroplasticity. Furthermore, we highlight the therapeutic potential of GAs for neurological disorders with impaired neuroplasticity as the core pathological mechanism and propose directions for future research to unlock their full clinical utility.