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Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
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In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
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Modeling Chemotherapy Resistant Leukemia In Vitro
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Chemotherapy and the pediatric brain.

Chrysanthy Ikonomidou1

  • 1Department of Neurology, Section of Child Neurology, University of Wisconsin Madison, Madison, WI, 53705, USA. ikonomidou@neurology.wisc.edu.

Molecular and Cellular Pediatrics
|November 8, 2018
PubMed
Summary

Chemotherapy can harm the developing brains of children with cancer, leading to neurocognitive deficits. Understanding these neurotoxic effects is crucial for improving survivors' quality of life.

Area of Science:

  • Pediatric Oncology
  • Neuroscience
  • Cancer Therapeutics

Background:

  • Childhood cancer survival rates are increasing, highlighting the need to address long-term neurocognitive and psychiatric outcomes.
  • Neurobehavioral morbidity, including cognitive deficits and emotional health issues, significantly impacts the quality of life for childhood cancer survivors.
  • Chemotherapy-induced central nervous system (CNS) toxicity is a major contributor to neurobehavioral issues in these survivors.

Purpose of the Study:

  • To review key publications on chemotherapy neurotoxicity in pediatric cancers.
  • To summarize the potential underlying pathomechanisms of chemotherapy-induced brain injury in children.
  • To inform clinical practice and future research regarding neuroprotection strategies.

Main Methods:

Keywords:
Brain injuryCognitionDisease mechanismsNeurotoxicity

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  • Literature review of clinical and preclinical studies.
  • Analysis of studies investigating chemotherapy effects on the pediatric central nervous system (CNS).
  • Examination of mechanisms including excitotoxicity, apoptosis, DNA damage, oxidative stress, telomere shortening, and impaired neurogenesis.

Main Results:

  • Clinical studies link chemotherapy to leukoencephalopathies and reduced grey/white matter volumes, correlating with neurocognitive deficits.
  • Preclinical research demonstrates chemotherapy drugs are neurotoxic, causing brain injury via excitotoxic and apoptotic pathways.
  • Chemotherapy impacts developing brains by affecting myelination, synaptogenesis, neurogenesis, and neuronal network formation.

Conclusions:

  • Chemotherapy poses significant risks to neurodevelopment in children undergoing cancer treatment.
  • Understanding the molecular and cellular mechanisms of neurotoxicity is essential for mitigating long-term effects.
  • Further research is needed to develop strategies for neuroprotection in pediatric cancer patients.