• 6‐min walk test
• follow‐up
• heart transplantation
• pediatric
• physical performance capacity

• Humans
• Heart Transplantation
• Male
• Female
• Walk Test/methods
• Child
• Adolescent
• Follow-Up Studies
• Physical Functional Performance
• Prognosis
• Case-Control Studies
• Transplant Recipients
• Child, Preschool
• Exercise Tolerance
• Exercise Test
• Walking/physiology
• Muscle Strength

• Foundation for Pediatric Research and HUS Helsinki University Hospital

• CYP induction
• case report
• nirmatrelvir/ritonavir
• systemic lupus erythematosus
• tacrolimus

• Drug-induced posterior reversible encephalopathy syndrome
• FAERS
• PRES
• adverse drug reaction
• pharmacovigilance

• Humans
• Posterior Leukoencephalopathy Syndrome/chemically induced
• Posterior Leukoencephalopathy Syndrome/epidemiology
• Adverse Drug Reaction Reporting Systems/statistics & numerical data
• Male
• Female
• Retrospective Studies
• Databases, Factual
• United States Food and Drug Administration
• United States/epidemiology
• Pharmacovigilance
• Glucocorticoids/administration & dosage
• Glucocorticoids/adverse effects
• Middle Aged
• Adult
• Immunosuppressive Agents/adverse effects
• Immunosuppressive Agents/administration & dosage
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/administration & dosage
• Adolescent
• Aged
• Young Adult
• Sex Factors
• Child
• Drug-Related Side Effects and Adverse Reactions/epidemiology

• C0/D ratio
• LCPT
• extended-release tacrolimus
• fast metabolizer
• immunosuppression
• kidney transplantation
• quality of life
• tremor

• Humans
• Tacrolimus/administration & dosage
• Tacrolimus/pharmacokinetics
• Kidney Transplantation
• Female
• Male
• Middle Aged
• Delayed-Action Preparations
• Immunosuppressive Agents/administration & dosage
• Immunosuppressive Agents/pharmacokinetics
• Prospective Studies
• Quality of Life
• Adult
• Aged
• Tremor/drug therapy
• Drug Administration Schedule
• Longitudinal Studies
• Transplant Recipients

• Schmahmann's syndrome
• ataxia
• cerebellar syndrome
• hypomagnesemia
• ocular flutter

Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.

• Alcohol
• Liver transplantation
• Long term survival
• Metabolic syndrome
• Renal dysfunction
• Therapy adherence

• Sirolimus
• adverse effects
• everolimus
• hepatocellular carcinoma
• liver transplantation
• mTORi

Background: Cyclosporine is widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events profiles associated with cyclosporine in transplant patients using a spontaneous reporting system database.

Methods: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database, with the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event.

Results: The database comprised 3,327, 958, and 956 reports associated with cyclosporine in the kidney, stem cell, and heart transplant patients, respectively. Infectious and renal disorders were commonly detected in these transplant patients. The signal scores of cyclosporine for toxic nephropathy were noteworthy in the kidney (ROR: 15.1, 95% CI: 11-20.8) and stem cell (ROR, 216; 95% CI, 29.3-1593) transplantation. Cyclosporine in heart transplantation was strongly associated with gastric cancer (ROR, 39.4; 95% CI, 16.7-93.2), but not kidney or stem cell transplantation.

Conclusion: It was suggested that there is a diversity in the strength of the association between cyclosporine and adverse events in the kidney, stem cell, and heart transplantation. Our results may provide useful information for treatment with cyclosporine, although further research with more data is needed.

• CT
• EEG
• MRI
• chronic liver disease
• cirrhosis
• hepatic encephalopathy
• ictal blinking

• Cysteamine
• Myopathy
• Nephropathic cystinosis
• Nerve conduction studies/electromyography
• Neuromuscular
• Neuropathy

• brain repair
• demyelination diseases
• hematopoietic stem cell gene therapy
• hematopoietic stem cell transplantation
• leukodystrophy
• microglia
• neurological disorder

Posterior reversible encephalopathy syndrome (PRES) is a disorder that most commonly affects adults, and is characterized by neurologic symptoms such as encephalopathy, seizures, headaches, and visual disturbances. It usually occurs in the context of other systemic disturbances that result in hypertensive crises, such as renal failure, cytotoxic drugs, and autoimmune conditions. In children, it rarely manifests following chemotherapy induction or hematopoietic stem cell transplantation. No cases have been reported in the English literature connecting renal dysfunction and hypertensive emergency secondary to post-streptococcal glomerulonephritis (PSGN) with PRES. We present a case of an eight-year-old boy, who developed a constellation of symptoms suggestive of PSGN and later developed PRES. PRES is often confirmed upon suspicion through brain MRI showing subcortical edema of various brain regions including occipital, temporal, or parietal cortices. Our patient demonstrated subcortical edema of the bilateral occipital lobes and right cerebellar hemisphere, with positive antistreptolysin O (ASO) titers demonstrating PSGN as the likely etiology for his hypertensive emergency. Management included antihypertensive and anticonvulsant treatment, which allowed the resolution of the offending hypertensive emergency that resulted in PRES. Our case adds to the growing body of literature on PRES and describes a new etiology of pediatric PRES secondary to PSGN.

It is not known whether hearing disorders improves with kidney transplantation. One of the neurotoxic effects of immunosuppressive drugs may be unrecognized hearing loss. In this study, our aim was to evaluate the hearing disorders in kidney transplant patients. Hearing problems in 46 kidney transplant patients [eGFR ≥ 60 ml/min/1.73 m² (30 Tacrolimus, 16 mTOR inhibitor users)], 23 hemodialysis patients, and 20 healthy controls were evaluated with a questionnaire and high-frequency audiometry. More than half (58.7%) of the transplant patients had at least one hearing problem. Hearing loss was observed in 50%, 60.9% and 76.1% of the transplant patients at 8,000, 16,000 and 20,000 Hz. Hearing thresholds of transplant and hemodialysis patients increased from 4,000 to 20,000 Hz and was higher than that of controls. Hearing thresholds were higher at 1,000–2,000 Hz in patients using tacrolimus and at 16,000–20,000 Hz in patients using mTOR inhibitor. No correlation was found between hearing threshold and blood tacrolimus or mTOR inhibitor levels. Most kidney transplant and hemodialysis patients have hearing loss at higher frequencies than medium frequencies. Hearing loss in chronic kidney patients is likely to be permanent and kidney transplantation may not improve hearing problems. Hearing problems may be more pronounced at medium frequencies in patients receiving tacrolimus but at higher frequencies in patients receiving mTOR inhibitors.

• extended high-frequency audiometry
• hearing impairment
• hemodialysis
• immunsuppressants
• kidney transplantation

• Calcineurin inhibitors
• Kidney transplant
• Rapamycin
• Substantia nigra echogenic area
• Third ventricle width
• Transcranial sonography

• Adolescents
• Brain structure
• Chronic kidney disease
• Kidney failure
• Kidney replacement therapy
• Magnetic resonance imaging

• Ataxia
• Bipolar disorder
• Neurotoxicity
• Status epilepticus
• Tacrolimus

• GvHD
• T cells
• central nervous system
• drug toxicity
• inflammation
• microglia

• Acute Disease
• Allografts/immunology
• Animals
• Anti-Infective Agents/adverse effects
• Anti-Infective Agents/therapeutic use
• Central Nervous System/drug effects
• Central Nervous System/immunology
• Central Nervous System Diseases/etiology
• Central Nervous System Diseases/immunology
• Central Nervous System Infections/drug therapy
• Central Nervous System Infections/immunology
• Cerebrovascular Disorders/etiology
• Cerebrovascular Disorders/immunology
• Disease Models, Animal
• Female
• Graft vs Host Disease/diagnosis
• Graft vs Host Disease/etiology
• Graft vs Host Disease/immunology
• Graft vs Host Disease/prevention & control
• Hematopoietic Stem Cell Transplantation/adverse effects
• Humans
• Immunosuppressive Agents/adverse effects
• Immunosuppressive Agents/therapeutic use
• Male
• Mice
• Primates
• T-Lymphocytes/immunology
• T-Lymphocytes/transplantation

• Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
• Deutsche Forschungsgemeinschaft

A 58-year-old man, incapable of maintaining oxygen saturation with mechanical ventilation, was admitted to our hospital for veno-venous extracorporeal membrane oxygenation (ECMO) treatment. He was diagnosed with acute respiratory distress syndrome (ARDS) due to influenza A pneumonia. His condition stabilized with antibiotics and steroid administration, but weaning from ECMO failed due to post-infectious pulmonary sequelae. On day 84 after admission, he underwent bilateral lung transplantation. In the postoperative phase, he did not regain consciousness even after discontinuation of sedatives for 3 days. However, spontaneous pupillary reflex and eye movements were preserved, while communication and upper and lower limb movements were affected. The nerve conduction study was diagnostic of Guillain-Barré syndrome. He was managed with intravenous immunoglobulins and plasmapheresis. Mild recovery of the facial muscles was seen, but he died 24 days post-surgery due to progressive ARDS and sepsis.

• Acute respiratory distress syndrome
• Case report
• Complication
• Extracorporeal circulation
• Guillain-Barre syndrome
• Lung transplantation

• Neuropsychiatric side effects
• Neurotoxic
• Psychosis
• Tacrolimus

• arthritis
• biomarkers
• equine
• prolonged-action preparation
• synovial fluid
• tacrolimus

• Huntington's disease
• humanization
• mouse model
• neuroinflammation
• stem cells

• Animals
• Disease Models, Animal
• Disease Progression
• Humans
• Huntington Disease/physiopathology
• Huntington Disease/therapy
• Mesenchymal Stem Cell Transplantation
• Mice
• Mice, Transgenic
• Neuroinflammatory Diseases/physiopathology
• Neuroinflammatory Diseases/therapy

• P30 CA093373 NCI NIH HHS
• S10 OD018223 NIH HHS
• S10 RR026825 NCRR NIH HHS
• UL1 TR001860 NCATS NIH HHS
• R24ODO21606 NINDS NIH HHS
• R01 NS102486 NINDS NIH HHS
• C06 RR012088 NCRR NIH HHS
• T32 GM099608 NIGMS NIH HHS
• R24 201603716 NINDS NIH HHS
• R24 OD021606 NIH HHS
• S10 RR12964 NIH NCRR
• P50 HD103526 NICHD NIH HHS
• NCI
• NINDS

• Immunology
• Organ transplantation
• Signal transduction

This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson’ disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson’s disease between 2007 and 2015. We established two control cohorts without a history of Parkinson’ disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson’s disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson’ disease. Risk of incident Parkinson’s disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson’s disease in KT recipients.

• clinical research / practice
• editorial / personal viewpoint
• immunosuppressant - fusion proteins and monoclonal antibodies
• immunosuppression / immune modulation
• immunosuppressive regimens - maintenance
• kidney transplantation / nephrology
• kidney transplantation: living donor
• off-label drug use
• rejection: acute

• hepatocellular carcinoma
• immunosuppressant
• liver transplantation
• mycophenolate mofetil
• population-based study
• recommended defined daily dose
• recurrence

Often described as a clinico-radiological entity, posterior reversible encephalopathy syndrome (PRES) is being increasingly diagnosed nowadays. However, mystery still surrounds its exact etiology. Though there are no standardized diagnostic criteria for this syndrome, there is a consistent feature associated with it: brain vasogenic edema in combination with neurotoxicity. The nonspecific nature of this condition leaves room for the diagnosis to be overlooked, leading to delays in providing appropriate treatment and unfavorable patient outcomes. PRES is associated with a variety of medical conditions including hypertension, eclampsia, autoimmune conditions, renal failure, sepsis, and an immunocompromised state, such as that secondary to the use of immunosuppressive therapy, human immunodeficiency virus (HIV), and organ transplants. Treatment by a multidisciplinary team and prompt identification and reversal of the underlying cause can lead to beneficial outcomes, as in the case we present in this report.

• critical care
• nephrology
• posterior reversible encephalopathy syndrome (pres)
• radiology

• G-ratio
• neurotoxic effects
• sciatic nerve
• tacrolimus (FK506)
• ultrastructure

Regulation of calcineurin, a Ca²⁺/calmodulin-regulated phosphatase, is important for the nervous system, and its abnormal activity is associated with various pathologies, including neurodegenerative disorders. In yeast cells lacking the VPS13 gene (vps13Δ), a model of VPS13-linked neurological diseases, we recently demonstrated that calcineurin is activated, and its downregulation reduces the negative effects associated with vps13Δ mutation. Here, we show that overexpression of the RCN2 gene, which encodes a negative regulator of calcineurin, is beneficial for vps13Δ cells. We studied the molecular mechanism underlying this effect through site-directed mutagenesis of RCN2. The interaction of the resulting Rcn2 variants with a MAPK kinase, Slt2, and subunits of calcineurin was tested. We show that Rcn2 binds preferentially to Cmp2, one of two alternative catalytic subunits of calcineurin, and partially inhibits calcineurin. Rcn2 ability to bind to and reduce the activity of calcineurin was important for the suppression. The binding of Rcn2 to Cmp2 requires two motifs in Rcn2: the previously characterized C-terminal motif and a new N-terminal motif that was discovered in this study. Altogether, our findings can help to better understand calcineurin regulation and to develop new therapeutic strategies against neurodegenerative diseases based on modulation of the activity of selected calcineurin isoforms.

• Rcn2
• Vps13
• calcineurin
• calcium signaling
• neurodegenerative diseases
• yeast model

• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Binding Sites
• Calcineurin/metabolism
• Gene Dosage
• Gene Expression Regulation
• Mutation
• Protein Binding
• Protein Interaction Domains and Motifs
• Vesicular Transport Proteins/deficiency

A large number of neurological disorders can affect renal transplant recipients, potentially leading to disabling or life-threatening complications. Prevention, early diagnosis and appropriate management of these conditions are critical to avoid irreversible lesions. A pivotal role in the pathogenesis of common post-transplant neurological disorders is played by immunosuppressive therapy. The most frequently administered regimen consists of triple immunosuppression, which comprises a calcineurin inhibitor (CNI), a purine synthesis inhibitor and glucocorticoids. Some of these immunosuppressive drugs may lead to neurological signs and symptoms through direct neurotoxic effects, and all of them may be responsible for the development of tumors or opportunistic infections. In this review, after a brief summary of neurotoxic pathogenetic mechanisms encompassing recent advances in the field, we focus on the clinical presentation of more common and severe immunosuppression-related neurological complications, classifying them by characteristics of urgency and anatomic site. Our goal is to provide a general framework that addresses such clinical issues with a multidisciplinary approach, as these conditions require.

• Immunosuppressive drugs
• Nervous system
• Neurological disorders
• Renal transplantation

• Calcineurin Inhibitors/adverse effects
• Graft Rejection/prevention & control
• Humans
• Immunosuppression Therapy/adverse effects
• Immunosuppressive Agents/adverse effects
• Kidney Transplantation/adverse effects
• Nervous System Diseases/chemically induced
• Nervous System Diseases/diagnosis

• Università degli Studi di Milano

Cytomegalovirus (CMV)‐related encephalitis is a rare but potentially life‐threatening complication of CMV infection in immunocompromised patients. The high mortality rate is associated with deficient immune system reconstitution after hematopoietic stem cell transplant (HSCT) and poor bioavailability of antiviral drugs in cerebrospinal fluid (CSF). CMV‐related central nervous system (CNS) infection may occur with aspecific symptoms, without evidence of either blood viral load or magnetic resonance imaging (MRI) signs of encephalitis.

Here, we describe a 10‐year‐old girl who underwent an allogeneic HSCT and subsequently developed CMV encephalitis. Because of the absence of CMV antigen in the blood, the diagnosis of encephalitis was proposed only after a delay, following the onset of immune reconstitution inflammatory syndrome (IRIS). Two months of combined dual antiviral therapy with ganciclovir and foscarnet proved ineffective against CMV and caused significant bone marrow and renal toxicity. To avoid further toxicity, the girl was given daily treatment with CMV‐hyperimmune globulins alone.

After three weeks, the CSF viral load dropped significantly and was undetectable within three more weeks. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery.

We suggest that this patient succeeded in achieving CMV CSF clearance with high dose of CMV‐hyperimmune globulin, given alone, because of the ability of immunoglobulins to penetrate the blood–brain barrier (BBB).

• CMV‐hyperimmune globulin
• IL‐6
• cerebrospinal fluid CMV antibodies
• cytomegalovirus (CMV)‐related encephalitis
• immune reconstitution inflammatory syndrome (IRIS)

• 11β,13-dihydrolactucin
• 11β,13-dihydrolactucopicrin
• NFAT
• calcineurin
• lactucin
• lactucopicrin

• Anti-Inflammatory Agents/pharmacology
• Cichorium intybus
• Humans
• In Vitro Techniques
• Intestines/drug effects
• Lactones/pharmacology
• Permeability
• Sesquiterpenes/pharmacology

• 760891 EU Horizon 2020 Research & Innovation Programme

• ESKD
• acute kidney injury and ICU nephrology
• calcineurin inhibitors
• chronic
• cognitive dysfunction
• comorbidity
• immunosuppression
• infections
• kidney failure
• kidney transplantation
• neurological complications
• seizures

• movement disorders
• nephropathy
• neurogenetics.

Tacrolimus has been used to induce remission in patients with steroid-refractory ulcerative colitis. It poses a problem of large individual differences in dosage necessary to attain target blood concentration and, often, this leads to drug inefficacy. We examined the difference in mRNA expression levels of ATP binding cassette transporter B1 (ABCB1) between inflamed and non-inflamed tissues, and the influence of CYP3A5 genotype on tacrolimus therapy. The mRNA expression of CYP3A4 in colonic mucosa and that of cytochrome p450 3A5 (CYP3A5) and ABCB1 in inflamed and non-inflamed areas were examined in 14 subjects. The mRNA expression levels of CYP3A5 were higher than that of CYP3A4. The mRNA expression of ABCB1 was lower in the inflamed than in the non-inflamed mucosa, despite that of CYP3A5 mRNA level being not significantly changed. Hence, the deterioration of the disease is related to the reduction of the barrier in the inflamed mucosa. The relationship between CYP3A5 genotype and blood concentration, dose, and concentration/dose (C/D) ratio of tacrolimus in 15 subjects was studied. The tacrolimus dose to maintain equivalent blood concentrations was lower in CYP3A5*3/*3 than in CYP3A5*1 carriers, and the C/D ratio was significantly higher in the latter. Thus, CYP3A5 polymorphism information played a role in determining the initial dose of tacrolimus. Furthermore, since the effect of tacrolimus appears earlier in CYP3A5*3/*3 than in CYP3A5*1/*1 and *1/*3, it seems necessary to change the evaluation time of therapeutic effect by CYP3A5 genotype. Additionally, the relationship between CYP3A5 genotype and C/D ratio of tacrolimus in colonic mucosa was investigated in 10 subjects. Tacrolimus concentration in the mucosa was two-fold higher in CYP3A5*3/*3 than in CYP3A5*1 carriers, although no significant difference in tacrolimus-blood levels was observed. Therefore, the local concentration of tacrolimus affected by CYP3A5 polymorphism might be related to its therapeutic effect.

• clinical activity index
• inflammatory bowel disease
• mucosal concentration
• multidrug resistance 1
• polymorphism

• Calcineurin inhibitors
• Cyclosporine
• Drug toxicity
• Kidney transplantation
• Tacrolimus

Nuclear factor of activated T cells (NFATs) is an important transcription factor for T cell activation and proliferation. Recent studies have highlighted the role of NFATs in regulating the differentiation of effector CD4 T helper (Th) subsets including Th1 and Th17 cells. Because controlling the effector T cell function is important for the treatment of autoimmune diseases, regulation of NFAT functions in T cells would be an important strategy to control the pathogenesis of autoimmune diseases. Here, we demonstrated that an NFAT inhibitory peptide, VIVIT conjugated to dNP2 (dNP2-VIVIT), a blood-brain barrier-permeable peptide, ameliorated experimental autoimmune encephalomyelitis (EAE) by inhibiting Th1 and Th17 cells, but not regulatory T (T_reg) cells. dNP2-VIVIT negatively regulated spinal cord-infiltrating interleukin-17A (IL-17A) and interferon (IFN)-γ-producing CD4⁺ T cells without affecting the number of Foxp3⁺ CD4⁺ T_reg cells, whereas dNP2-VEET or 11R-VIVIT could not significantly inhibit EAE. In comparison with cyclosporin A (CsA), dNP2-VIVIT selectively inhibited Th1 and Th17 differentiation, whereas CsA inhibited the differentiation of all T cell subsets including that of Th2 and T_reg cells. Collectively, this study demonstrated the role of dNP2-VIVIT as a novel agent for the treatment of autoimmune diseases such as multiple sclerosis by regulating the functions of Th1 and Th17 cells.

• Cell penetrating peptide (CPP)
• Multiple sclerosis (MS)
• T cell
• VIVIT
• dNP2

• Immunosuppressive agents
• Organ transplantation
• Posterior reversible encephalopathy syndrome
• Postoperative complications
• Stem cell transplantation

• fkbp ligands
• regenerative medicine
• nonimmunosuppressive
• bmp signaling
• smad1/5
• fkvp
• calcineurin

• T32 GM080189 NIGMS NIH HHS

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.

• alloimmune response
• calcineurin inhibitors
• corticosteroids
• immunosuppressants
• mTOR inhibitors
• neuroprotective effects
• neurotoxicity

• Brain-derived neurotrophic factor
• Diabetes
• Hippocampal dysfunction
• Interneuron
• Mossy fiber
• Tacrolimus

• Kidney transplantation
• immunosuppression
• nervous system diseases

• cirrhosis
• cognitive impairment
• hepatic encephalopathy
• liver transplantation

• AMD3100
• FK506
• FKBP
• bone morphogenic protein
• stem cells
• wound healing