PMID- 31261959
OWN - NLM
STAT- MEDLINE
DCOM- 20191203
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 13
DP  - 2019 Jun 29
TI  - Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related 
      Neurotoxicities.
LID - 10.3390/ijms20133210 [doi]
LID - 3210
AB  - 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.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of 
      Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
FAU - Egashira, Nobuaki
AU  - Egashira N
AUID- ORCID: 0000-0002-3673-6824
AD  - Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of 
      Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. 
      n-egashi@pharm.med.kyushu-u.ac.jp.
AD  - Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan. 
      n-egashi@pharm.med.kyushu-u.ac.jp.
FAU - Masuda, Satohiro
AU  - Masuda S
AUID- ORCID: 0000-0002-3589-5989
AD  - Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of 
      Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
AD  - Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
LA  - eng
GR  - 17K08953, 18H02588/Grant-in-Aid for Scientific Research (KAKENHI) from the 
      Ministry of Education, Science, Culture, Sports and Technology of Japan/
PT  - Journal Article
PT  - Review
DEP - 20190629
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Antimetabolites)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Adrenal Cortex Hormones/toxicity
MH  - Animals
MH  - Antimetabolites/toxicity
MH  - Calcineurin Inhibitors/toxicity
MH  - Humans
MH  - Immunosuppressive Agents/*toxicity
MH  - Neurotoxicity Syndromes/*etiology/metabolism/pathology
MH  - Protein Kinase Inhibitors/toxicity
PMC - PMC6651704
OTO - NOTNLM
OT  - alloimmune response
OT  - calcineurin inhibitors
OT  - corticosteroids
OT  - immunosuppressants
OT  - mTOR inhibitors
OT  - neuroprotective effects
OT  - neurotoxicity
COIS- The authors declare no conflict of interest.
EDAT- 2019/07/03 06:00
MHDA- 2019/12/04 06:00
PMCR- 2019/07/01
CRDT- 2019/07/03 06:00
PHST- 2019/05/29 00:00 [received]
PHST- 2019/06/26 00:00 [revised]
PHST- 2019/06/28 00:00 [accepted]
PHST- 2019/07/03 06:00 [entrez]
PHST- 2019/07/03 06:00 [pubmed]
PHST- 2019/12/04 06:00 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - ijms20133210 [pii]
AID - ijms-20-03210 [pii]
AID - 10.3390/ijms20133210 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jun 29;20(13):3210. doi: 10.3390/ijms20133210.