Document Type

Article

Publication Date

2023

Abstract

Background: The choroid plexus (CP), a highly vascularized organ that lines the ventricles of the brain, serves several important functions that maintain homeostasis of the cerebrospinal fluid (CSF) surrounding the brain and protect the brain from harmful contents by acting as a part of the blood-cerebrospinal fluid barrier (BCSFB). Dysfunction in CP morphology and function has recently been associated with various conditions such as stroke, aging, neoplasms, hydrocephalus, Alzheimer’s disease, depression, and psychosis. Substances of abuse poses a significant problem worldwide and are associated with significant morbidity, mortality and disease burden. CP dysfunction has also been documented for substance abuse; however, it is unclear whether the different kinds of abused substances may differentially impact CP dysfunction.

Methods: This systematic review explores the morphological changes in the CP associated with different kinds of abused substances. We conducted a comprehensive literature search for commonly abused substances including alcohol, cocaine, cannabis, methamphetamine/ amphetamine, opioids, hallucinogens, tobacco/nicotine using PubMed, Web of Science, MEDLINE, and Google Scholar. Only studies of CP morphological changes from alcohol, cocaine, methamphetamine, tobacco/nicotine, and opioids (morphine) were found. Articles were selected based on whether CP morphology in the use of illicit substances was assessed using imaging techniques such as magnetic resonance imaging (MRI) computed tomography (CT), ultrasound (US), light microscopy, and transmission electron microscopy (TEM). Studies included basic animal research as well as studies focusing on the effects of substance use in pregnant mothers and their embryos/fetuses.

Results: The results revealed that morphological changes of the CP were observed in the context of the previously mentioned substances. Alcohol consumption during pregnancy was found to be associated with substantial abnormalities in CP epithelium. Studies reported CP hyperplasia or agenesis, increased lateral ventricle volume, decreased glycogen content, and enlarged intercellular spaces. Ultrastructural changes such as dilated intercellular spaces, disrupted mitochondria, aggregation of primary and secondary lysosomes, and vacuoles within the cytoplasm were observed in rats exposed to alcohol. Cocaine use was found to potentially induce CP damage. In rats, vacuolization, necrosis, and lesions CP blood vessels were noticed. Human maternal cocaine use resulted in cases of CP cysts in different studies, but it was determined to be difficult to establish a direct correlation. The administration of methamphetamine in rats resulted in an increase in CP volume, destroyed nuclei, and elevated capillary quantity. Administration of oral morphine to rats led to dysfunctional synthesis and secretion of CSF by the CP, resulting in decreased cavity surface area and increased CP surface area, which may be attributed to ependymal cell proliferation, vasoconstriction, and abnormal CSF secretion caused by morphine. Maternal smoking was found to have a significant impact on the CP of the fourth ventricle in fetuses and infants who were victims of sudden death syndromes.

Conclusion: These findings highlight the vulnerability of the CP to substances of abuse and the potential impact on CSF production, CSF homeostasis, and brain development. Understanding these effects may provide insight into the mechanisms underlying the pathophysiology associated with substance abuse and contribute to the development of targeted interventions and preventive strategies. Further research is necessary to study the complex interaction between substance abuse and the CP, considering confounding variables and having an emphasis on non-invasive imaging techniques to translate research to adult humans.

Academic Level

medical student

Mentor/PI Department

Neuroscience

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