Hyper IgE in Childhood Eczema and Risk of Asthma in Chinese Children.

BACKGROUND: Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. METHODS: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test (SPT) for common food and aeroallergens, highest serum IgE ever and eosinophil counts were evaluated in 330 children eczema patients. Childhood-NESS (NESS performed at <10 years of age) and adolescent-NESS (NESS performed at >10 years of age) were further analyzed. RESULTS: IgE correlated with NESS (spearman coefficient 0.35, p < 0.001) and eosinophil percentage (spearman coefficient 0.56, p = 0.001). Compared with IgE ≤ 2000IU/L (n = 167), patients with hyper-IgE (n = 163) were associated with male gender (p = 0.002); paternal atopy (p = 0.026); personal history of atopic rhinitis (p = 0.016); asthma (p < 0.001); dietary avoidance (p < 0.001); use of wet wrap (p < 0.001); traditional Chinese medicine use (TCM, p < 0.001); immunomodulant use (azathioprine or cyclosporine, p < 0.001); skin prick sensitization by dust mites (p < 0.001), cats (p = 0.012), dogs (p = 0.018), food (p = 0.002); eosinophilia (p < 0.001); more severe disease during childhood (p < 0.0001) and during adolescence (p < 0.0001), but not onset age of eczema or maternal atopy. Logistic regression showed that hyper-IgE was associated with personal history of asthma (exp(B) = 5.12, p = 0.002) and eczema severity during childhood and adolescence (p < 0.001). For patients <10 years of age, dust mite sensitization (p = 0.008) was associated with hyper-IgE. For patients >10years of age, food allergen sensitization was associated with hyper-IgE (p = 0.008). CONCLUSIONS: Hyper-IgE is independently associated with asthma, more severe atopy and more severe eczema during childhood and adolescence. IgE > 2000 IU/L may be a tool to aid prognostication of this chronic relapsing dermatologic disease and its progression to asthma.

Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin.

BACKGROUND: Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. METHODS AND RESULTS: In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. CONCLUSIONS: These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Relevance of Cat and Dog Sensitization by Skin Prick Testing in Childhood Eczema and Asthma.

BACKGROUND: Household animal dander has been implicated as aeroallergen in childhood atopic diseases. Many parents seek healthcare advice if household pet keeping may be detrimental in atopic eczema (AE), allergic rhinitis and asthma. AIM: We investigated if skin sensitization by cat/dog dander was associated with disease severity and quality of life in children with AE. METHODS: Demographics, skin prick test (SPT) results, disease severity (Nottingham eczema severity score NESS), Children Dermatology Life Quality Index (CDLQI), blood IgE and eosinophil counts of a cohort of AE patients were reviewed. RESULTS: 325 AE patients followed at a pediatric dermatology clinic were evaluated. Personal history of asthma was lowest (20%) in the dog-dander-positive-group but highest (61%) in bothcat- and-dog-dander-positive group (p=0.007). Binomial logistic regression ascertained that catdander sensitization was associated with increasing age (adjusted odds ratio [aOR], 1.056; 95% Confidence Interval [CI], 1.006 to 1.109; p=0.029), dust-mite sensitization (aOR, 4.625; 95% CI, 1.444 to 14.815; p=0.010), food-allergen sensitization (aOR, 2.330; 95% CI, 1.259 to 4.310; p=0.007) and keeping-cat-ever (aOR, 7.325; 95% CI, 1.193 to 44.971; p=0.032); whereas dogdander sensitization was associated with dust-mite sensitization (aOR, 9.091; 95% CI, 1.148 to 71.980; p=0.037), food-allergen sensitization (aOR, 3.568; 95% CI, 1.341 to 9.492; p=0.011) and keeping-dog-ever (aOR, 6.809; 95% CI, 2.179 to 21.281; p=0.001). However, neither cat nor dog sensitization were associated with asthma, allergic rhinitis, parental or sibling atopic status, disease severity or quality of life. CONCLUSION: Physicians should advise parents that there is no direct correlation between AE severity, quality of life, asthma or allergic rhinitis with cutaneous sensitization to cats or dogs. Sensitized patients especially those with concomitant asthma and severe symptoms may consider non-furry alternatives if they plan to have a pet. Highly sensitized individuals, especially those with asthma co-morbidity, may have to remove their pet for a trial period to determine if symptoms improve.

Objective measurement of two clinical signs in childhood atopic eczema in research and therapeutics.

BACKGROUND: Atopic dermatitis (AD) or eczema is an inflammatory skin disease associated with significant impairment of quality of life. It is important to objectively quantify cutaneous biophysical measurements in research and therapeutics of this disease. OBJECTIVE: To evaluate if skin redness (erythema) and pigmentation (melanin) correlate with disease severity and quality of life. METHODS: Redness and pigmentation were measured under standardized condition at the antecubital flexure. Nottingham Eczema Severity Score (NESS) and Children's Dermatology Life Quality Index (CDLQI) were documented. RESULTS: Pigmentation correlated with age (r = 0.38, p = 0.02), but not with disease severity (NESS) or quality of life (CDLQI). Erythema correlated with age (r = 0.53, p = 0.001), NESS (r = 0.44, p = 0.006), pigmentation (r = 0.62, p< 0.0001), but not CDLQI (r = 0.3, trend p = 0.087). CONCLUSIONS: Skin erythema and pigmentation increase with age. Erythema correlates with disease severity but pigmentation correlates with neither severity nor quality-of-life score. The objective measurement of these two signs does not replace the clinical measurements of severity and quality of life, and may be of limited scope in eczema research and therapeutics.

Predicting eczema severity beyond childhood.

BACKGROUND: We evaluated factors associated with eczema severity in adolescence. METHODS: Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test for common food and aeroallergens, highest serum IgE level and eosinophil count were evaluated. Patients with paired NESSs (childhood-NESS is NESS performed at <10 years of age; adolescence-NESS is NESS performed at age >10 years) were further analyzed. RESULTS: Adolescence-NESS (n=383 patients) was associated with eczema onset in infancy, dust mite and food allergen sensitization, dietary avoidance, use of wet wrap, traditional Chinese medicine, immunomodulant (azathioprine or cyclosporine), high IgE level, eosinophil count, but not with family/personal history of atopy. Eighty-two patients had both childhood-NESS and adolescence-NESS (mean follow-up of 6.8 years) showing that adolescence-NESS was associated with childhood- NESS severity grades (P=0.034). Of these patients, 48% remained in the same severity grades, whereas 39% improved, and 13% deteriorated from childhood to adolescence. CONCLUSIONS: It is not possible to assure parents that their child can outgrow eczema. In eczema prognosis research, long-term follow-up is warranted.

Correlations among steroid fear, acceptability, usage frequency, quality of life and disease severity in childhood eczema.

UNLABELLED: Topical corticosteroids (CSs) are the mainstay of treatment for eczema but CS phobia and fears are prevalent and influence therapeutic efficacy. AIM: To quantify if CS acceptability and fear affect patients' quality-of-life (QoL). METHODS: Patients with eczema managed in the pediatric dermatology outpatient clinic of a university hospital were surveyed. Nottingham Eczema Severity Score (NESS) for severity, Children's Dermatology Life Quality Index (CDLQI) for QoL, CS fear, acceptability and reported frequency of CS use were measured with quantified questions. RESULTS: CS fears were prevalent among parents and caregivers of patients with eczema. Fifty-eight percent of parents reported general acceptability of CS as being very good or good, and many applied CS to their child regularly every week. However, >40% of parents reported CS fear "always" or "often", 41% reported that they "always" or "often" apply CS only when eczema got worse, 57% would discuss CS fear with their doctors, 30% would request CS-sparing medications and 14% "always" or "often" use traditional Chinese herbal medicine. Fears were predominantly interpersonal and less often iatrogenic in nature. Skin problems were the most concerned side effects of CS. CS acceptability, frequency of CS usage, CS fear and usage of alternative medications were independent domains in eczema management: CS fears correlated with CDLQI; CS usage frequency correlated with NESS and negatively with parental education; and CS acceptability correlated with parental education. Ordinal logistic regressions showed worse QoL was associated with more CS fear (odds ratio: 1.092 [95% CI: 1.023-1.165], p = 0.008). CONCLUSIONS: The extent of CS fears is independent of CS acceptability, but correlates with patients' QoL. Desensitization of parental CS fears should be integral part of eczema education and therapeutics in order to improve therapeutic efficacy and patients' QoL.

Specific IgG and IgA of common foods in Chinese children with eczema: friend or foe.

BACKGROUND: Specific immunoglobulins G and A (IgG and IgA) for common food items have been extensively measured as surrogate markers of food allergy, and dietary avoidance based on the test results advocated. AIM: We reviewed the prevalence of specific food IgG and IgA in children with eczema and evaluated outcome of dietary avoidance in these children. METHODS: Specific immunoglobulins of 96 food items were measured for 30 consecutive atopic dermatitis (AD) patients and disease severity [SCORing atopic dermatitis (SCORAD) and Nottingham eczema severity score (NESS)], Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL), topical corticosteroid and oral antihistamine usage were evaluated. Twenty seven of these patients received dietary avoidance advice based on IgG and IgA data. General acceptability of treatment (GAT) was documented at the end of 3 months. RESULTS: There were generally no correlations among levels of IgG or IgA of the 96 food items and disease severity, quality of life, SH or TEWL. Two-third patients reported very good or good and one-third reported fair or poor GAT following dietary avoidance advice. There was no difference in any clinical parameters between the two groups following dietary avoidance. Patient with lower sunflower seed IgA (p = 0.043), casein IgG (p = 0.041), milk IgG (p = 0.037) or whey IgG (p = 0.014) had improved SCORAD and objective SCORAD following dietary advice. CONCLUSION: Children with AD are sensitized to many food allergens via IgG and IgA mechanisms. Levels of food IgG or IgA do not seem to correlate with any clinical parameters in AD. Subjectively, two third of patients accepted dietary manipulations as very good or good for their AD. Objectively, dietary avoidance had few clinical effects on the clinical parameters. Sensitization should not be generalized to mean allergy to common food.

Circulating immunoglobulins, leucocytes and complements in childhood-onset atopic eczema.

OBJECTIVE: To evaluate if eczema severity is associated with blood levels of immunoglobulins, white cell differentials and complements. METHODS: White cell differentials, levels of serum immunoglobulins and complements of patients with eczema and miscellaneous non-eczema skin diseases were measured. Eczema severity and quality of life were assessed by SCORAD, Nottingham Eczema Severity Score (NESS) and Children's Dermatology Life Quality Index (CDLQI). Correlations were analyzed by Pearson's correlation test for parametric data and Spearman's rho correlation test for non-parametric data. RESULTS: Serum IgE and peripheral blood eosinophil percentage were significantly higher in patients with eczema than other non-eczema skin diseases. Levels of IgE (log-transformed), IgA and IgG correlated with objective SCORAD (r = 0.52, 0.40, 0.29, respectively). Levels of eosinophil, neutrophils, lymphocytes and complements also correlated with objective SCORAD, with the eosinohil/lymphocyte ratio showing the highest correlation (r = 0.60, p < 0.01). Ratios of IgE/IgA, IgE/IgG, eosinophils/lymphocytes, eosinophils/neutrophils correlated positively with CDLQI. IgM appeared to have no correlation with eczema. CONCLUSIONS: Blood levels of IgE, IgA, IgG,eosinophils, lymphocytes, neutrophils and complements pathophysiologically correlate with eczema severity. Eosinophil/lymphocyte ratio may represent a readily-available objective laboratory correlate of eczema severity. Eczema is a complex atopic disease involving many cellular and humoral components of the immune system.

The ideal moisturizer: a survey of parental expectations and practice in childhood-onset eczema.

AIM: We evaluated the moisturizing and bathing practices and preferences of patients with childhood-onset eczema. METHODS: The attitudes and practice of patients with eczema managed at a pediatric dermatology clinic were evaluated, using children with non-eczematous skin diseases as controls. Disease severity of eczema in the preceding 12 months was evaluated by the Nottingham Eczema Severity Score (NESS). Skin hydration (SH) and transepidermal water loss (TEWL) were assessed. RESULTS: Majority of patients took shower instead of bath and spent 12-13 min in shower. Most eczema patients applied emollients after shower/bath. Air-conditioning use was frequent, and patients with eczema maintained a lower ambient temperature than non-eczema patients (p = 0.001). Most eczema patients reported regular emollient usage (1.8 times/day for mild vs 2.8 times/day for moderate-to-severe eczema, p = 0.001), and acceptability of the current product was good to fair. Parents reported that the current emollients were most often recommended by doctors. Majority of parents/patients with mild eczema thought an ideal emollient needs only to be used twice a day whereas moderate-to-severe patients preferred more frequent usage (p = 0.001), and most of them preferred a non-fragrant, non-herbal white cream. Agreements concerning ideal emollient usage were only "moderate-to-fair" (kappa values <0.61), implying what parents/patients practiced was not the same as what they preferred. CONCLUSION: This study helps better understand the emolliation practices and preferences of eczema patients. Doctors remain the most important source of recommendation. Majority think an ideal moisturizer is a non-fragrant, non-herbal, white or transparent cream which needs only to be used two to three times per day. Compliance may be enhanced if the recommended moisturizer conforms to the parents/patients preference.

Acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors for atopic dermatitis in pediatric patients.

BACKGROUND: Atopic eczema or dermatitis (AD) is associated with atopy and is characterized by reduced skin hydration and an impaired skin barrier in the epidermis. We investigated the patient acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors (LMF) in AD. METHODS: Consecutive AD patients were recruited. Swabs and cultures were obtained from the right antecubital fossa and the worst-affected eczematous area, and disease severity [according to the SCORing Atopic Dermatitis (SCORAD) Index], skin hydration, and transepidermal water loss (TEWL) were measured prior to and after 2 weeks' use of the LMF moisturizer. The general acceptability of treatment was documented as being 'very good', 'good', 'fair', or 'poor'. RESULTS: Twenty-four AD patients [mean age 13.8 (standard deviation 5.7) years] were recruited. Two thirds of the patients reported very good or good acceptability of the LMF moisturizer, whereas one third reported fair or poor acceptability. There were no inter-group differences in the pre-use clinical parameters of age, objective SCORAD score, pruritus score, sleep disturbance score, skin hydration, TEWL, topical corticosteroid use, oral antihistamine use, or acceptability of previously used proprietary emollients. However, patients in the fair/poor acceptability group were more likely to have Staphylococcus aureus colonization and to be female (odds ratio 13, 95 % confidence interval 1.7-99.4; p = 0.021). Following use of the LMF moisturizer, the objective SCORAD score, pruritus score, and sleep disturbance score were lower in the very good/good acceptability group than in the fair/poor acceptability group. The mean objective SCORAD score improved (from 31.5 to 25.7; p = 0.039) and skin hydration improved [from 30.7 arbitrary units (a.u.) to 36.0 a.u.; p = 0.021] in the very good/good acceptability group. When the data were analyzed for the strength of the agreement of the rating of acceptability, the κ values were 0.338 (fair) for use of body wash and 0.118 (poor) for use of emollients before and after the trial. CONCLUSION: The LMF moisturizer was considered acceptable by two thirds of the patients with AD. It seems that patients who found the moisturizer acceptable were less likely to be female or to be colonized by S. aureus before switching to the product, and they had less severe eczema, less pruritus, and less sleep disturbance after its use than patients who did not find the product acceptable. Gender and S. aureus colonization may have influenced the patient acceptability and clinical efficacy of the LMF moisturizer. The lack of agreement with regard to the acceptability of the moisturizer implies that there is room for parent/patient education to improve compliance.

Thrombopoietin improved ventricular function and regulated remodeling genes in a rat model of myocardial infarction.

BACKGROUND: Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs). METHODS: Sprague-Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI+TPO. Three doses of TPO were administered weekly for 2 weeks, and outcomes were assessed at 4 or 8 weeks post-injury. RESULTS AND CONCLUSIONS: TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis.

OBJECTIVES: Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI). METHODS: Sprague-Dawley rats were randomly divided into four groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n = 9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured. RESULTS: Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P = 0.013) and improved cardiac functions in terms of fractional shortening (P = 0.004) and ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow-derived EPCs (P < 0.05) were higher in the MI + DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI + DZR animals (P = 0.043). CONCLUSIONS: Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.

Thrombopoietin protects against doxorubicin-induced cardiomyopathy, improves cardiac function, and reversely alters specific signalling networks.

AIMS: We investigated the therapeutic efficacy of thrombopoietin (TPO) in acute and chronic rat models of heart damage and explored the mechanisms in terms of genome-wide transcriptional changes, phosphorylation signals, and bone marrow endothelial progenitor cell (EPC) levels. METHODS AND RESULTS: Cardiac damage was induced in rat models of (i) acute-doxorubicin (DOX) treatment: single high-dose DOX, four doses TPO, followed up for 5 days; and (ii) chronic-DOX treatment: one low-dose DOX and three doses TPO weekly for 6 weeks, followed up for 11 weeks. Our results demonstrated that TPO treatment led to significant improvements of fractional shortening, cardiac output, and morphologic parameters in both models. In the acute-DOX model, microarray and network analyses showed that DOX damage was associated with changes in a large cohort of gene expressions, of which many were inversely regulated by TPO, including modulators of signal transduction, ion transport, anti-apoptosis, protein kinase B/ p42/p44 extracellular signal-regulated kinase (AKT/ERK) pathways, cell division, and contractile protein/matrix remodelling. Many of these regulations also occurred in chronic-DOX animals, in which TPO treatment reduced morphological damage and cardiomyopathy score, and increased AKT phosphorylation of heart tissues. Thrombopoietin also increased EPC colonies in their bone marrow. CONCLUSION: Our overall data suggest that TPO promotes cardiac protection from acute- and chronic-DOX insults, possibly mediated by multi-factorial mechanisms including AKT- and ERK-associated restoration of regulatory gene activities critical for normal heart function.

Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model.

PURPOSE: Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis. RESULTS: DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged. CONCLUSIONS: Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR.

Identification of TPO receptors on central nervous system-a preliminary report.

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.