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Review
. 2021 Jan 28;22(3):1281.
doi: 10.3390/ijms22031281.

The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

Justine Paris  1 , Eurydice Angeli  1   2   3 , Guilhem Bousquet  1   2   3
Affiliations
Review

The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

Justine Paris et al. Int J Mol Sci. .

Abstract

The incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood-brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood.

Keywords: blood–brain barrier; brain metastases; efflux receptor; glymphatic system; intrathecal injection; neonatal Fc receptor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Anatomical structures of brain vasculature. (a) The glymphatic system: xenobiotics circulation, diffusion and efflux along perivascular spaces after intrathecal administration. (b) Cross section of a brain vessel: xenobiotics circulate along perivascular spaces of blood vessels. A: astrocyte, regulator of the hydrostatic pressure by water exchanges; AQP4: aquaporin 4; P: pericyte; EC: endothelial cell; PVS: perivascular space; B: blood. (Images modified from © SMART/CC-BY-3.0).
Figure 2
Figure 2
Efflux systems on the BBB (blood–brain barrier). Left side: transcytosis across endothelial cells of the BBB by FcRn. Middle and right side: ABC transporters at the luminal side of endothelial cells of the BBB. ZO: zonula occludens. (Images modified from © SMART/CC-BY-3.0).
See this image and copyright information in PMC

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