Next Article in Journal
Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy
Next Article in Special Issue
NURR1 Impairment in Multiple Sclerosis
Previous Article in Journal
Mangifera indica L. Leaf Extract Induces Adiponectin and Regulates Adipogenesis
Previous Article in Special Issue
Purinergic Signaling and Cochlear Injury-Targeting the Immune System?
Open AccessReview

Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

1
Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
2
Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3210; https://doi.org/10.3390/ijms20133210
Received: 29 May 2019 / Revised: 26 June 2019 / Accepted: 28 June 2019 / Published: 29 June 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Neurotoxicity)
Although transplantation procedures have been developed for patients with end-stage hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity commonly occurs in clinical practice, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms through which CNIs cause neurotoxicity include increasing the permeability or injury of the blood–brain barrier, alterations of mitochondrial function, and alterations in the electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures, mycophenolate mofetil induces depression and headaches, methotrexate affects the central nervous system, the mouse monoclonal immunoglobulin G2 antibody (used against the cluster of differentiation 3) also induces headaches, and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms help reduce neurotoxic events considerably. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, combination therapy with drugs used to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize recent topics on the mechanisms of immunosuppressive drug-related neurotoxicity. In addition, information about the neuroprotective effects of several immunosuppressants is also discussed. View Full-Text
Keywords: alloimmune response; immunosuppressants; calcineurin inhibitors; corticosteroids; mTOR inhibitors; neurotoxicity; neuroprotective effects alloimmune response; immunosuppressants; calcineurin inhibitors; corticosteroids; mTOR inhibitors; neurotoxicity; neuroprotective effects
Show Figures

Figure 1

MDPI and ACS Style

Zhang, W.; Egashira, N.; Masuda, S. Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities. Int. J. Mol. Sci. 2019, 20, 3210.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop