Publications by authors named "Reilley Paige Mathena"

Exposure to general anesthetics can adversely affect brain development, but there is little study of sedative agents used in intensive care that act via similar pharmacologic mechanisms. Using quantitative immunohistochemistry and neurobehavioral testing and an established protocol for murine sedation, we tested the hypothesis that lengthy, repetitive exposure to midazolam, a commonly used sedative in pediatric intensive care, interferes with neuronal development and subsequent cognitive function via actions on the mechanistic target of rapamycin (mTOR) pathway. We found that mice in the midazolam sedation group exhibited a chronic, significant increase in the expression of mTOR activity pathway markers in comparison to controls.

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Patients who have undergone surgery in early life may be at elevated risk for suffering neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to the general anesthetic (GA) Isoflurane causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway.

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Persistent post-surgical pain (PPSP) is a chronic pain condition, often with neuropathic features, that occurs in approximately 20% of children who undergo surgery. The biological basis of PPSP has not been elucidated. Anesthetic drugs can have lasting effects on the developing nervous system, although the clinical impact of this phenomenon is unknown.

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Article Synopsis
  • Research shows that exposure to anesthetics or sedatives like midazolam during early life may negatively impact brain development, particularly in young patients who receive prolonged treatments in intensive care.
  • A study conducted on mice demonstrated that those sedated with midazolam in early postnatal life performed worse in cognitive tests and showed reduced adult neurogenesis in a critical brain area known for vulnerability to anesthetics.
  • The alterations included fewer presynaptic terminals and more excitatory postsynaptic terminals, indicating lasting changes in brain structure and function due to long-duration midazolam exposure.
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