Comparative Transcriptomic Analysis of Cerebellar Astrocytes across Developmental Stages and Brain Regions.

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these developmental timepoints. Moreover, we conducted a comparative analysis of cerebellar astrocyte gene signatures with gene lists from pediatric brain tumors of cerebellar origin, including ependymoma and medulloblastoma. Notably, genes downregulated at P14, such as Kif11 and HMGB2, exhibited significant enrichment across all pediatric brain tumor groups, suggesting the importance of astrocytic gene repression during cerebellar development to these tumor subtypes. Collectively, our studies describe gene expression patterns during cerebellar astrocyte development, with potential implications for pediatric tumors originating in the cerebellum.

Integrative Korean Medicine Treatments for Traumatic Facial Palsy Following Mandibular Fracture: A Case Report and Literature Review.

Prior studies exploring the effectiveness of traditional Korean medicine (TKM) treatment for facial palsy have mainly focused on Bell's palsy, and there are few studies on the effectiveness of TKM treatments for traumatic facial palsy following mandibular fracture. The patient was a 24-year-old Korean man with left-sided facial paralysis following a left mandibular fracture. Surgery was performed for the fracture and the facial palsy was treated using conventional medicine (CM) treatments for approximately 3 months, but there was no improvement observed in the patient's condition. Subsequently, the patient underwent an integrative Korean medicine treatment regimen consisting of acupuncture, pharmacopuncture, cupping, moxibustion, and herbal medication for a duration of 2 months. After 2 months of treatments, the House-Brackmann facial grading scale changed from Ⅴ to II and Yanagihara's unweighted grading score increased from 9 to 34. This case presentation and previous studies of traumatic facial palsy using TKM treatment show that TKM treatment may be considered a complementary or alternative treatment method to CM treatment in patients with traumatic facial palsy. PROSPERO registration number: CRD42023445051.

The genomic landscape of familial glioma.

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

The current status and outcomes of in-hospital P2Y12 receptor inhibitor switching in Korean patients with acute myocardial infarction.

BACKGROUND/AIMS: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. METHODS: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. RESULTS: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. CONCLUSION: In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

A Parkinson's disease gene, DJ-1, regulates anti-inflammatory roles of astrocytes through prostaglandin D2 synthase expression.

Dysfunctional regulation of inflammation may contribute to the progression of neurodegenerative diseases. The results of this study revealed that DJ-1, a Parkinson's disease (PD) gene, regulated expression of prostaglandin D2 synthase (PTGDS) and production of prostaglandin D2 (PGD2), by which DJ-1 enhanced anti-inflammatory function of astrocytes. In injured DJ-1 knockout (KO) brain, expression of tumor necrosis factor-alpha (TNF-α) was more increased, but that of anti-inflammatory heme oxygenase-1 (HO-1) was less increased compared with that in injured wild-type (WT) brain. Similarly, astrocyte-conditioned media (ACM) prepared from DJ-1-KO astrocytes less induced HO-1 expression and less inhibited expression of inflammatory mediators in microglia. With respect to the underlying mechanism, we found that PTGDS that induced expression of HO-1 was lower in DJ-1 KO astrocytes and brains compared with their WT counterparts. In addition, PTGDS levels increased in the injured brain of WT mice, but barely in that of KO mice. We also found that DJ-1 regulated PTGDS expression through Sox9. Thus, Sox9 siRNAs reduced PTGDS expression in WT astrocytes, and Sox9 overexpression rescued PTGDS expression in DJ-1 KO astrocytes. In agreement with these results, ACM from Sox9 siRNA-treated astrocytes and that from Sox9-overexpression astrocytes exerted opposite effects on HO-1 expression and anti-inflammation. These findings suggest that DJ-1 positively regulates anti-inflammatory functions of astrocytes, and that DJ-1 dysfunction contributes to the excessive inflammatory response in PD development.

Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry-National Institute of Health.

BACKGROUND: Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients. METHODS: Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry-National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded. RESULTS: After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6months was observed between two groups (4.2% vs. 4.9%, p=0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p=0.008; 3.8% vs. 2.5%, p=0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p<0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients≥75years or with body weight<60kg (odd ratio [OR]=3.209; 95% confidence interval [CI]=1.356-7.592) and in those received trans-femoral intervention (OR=1.996; 95% CI=1.061-3.754). CONCLUSIONS: Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI.

DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in brain microglia and astrocytes: A novel anti-inflammatory function of DJ-1.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder caused by the death of dopaminergic neurons in the substantia nigra. Importantly, altered astrocyte and microglial functions could contribute to neuronal death in PD. In this study, we demonstrate a novel mechanism by which DJ-1 (PARK7), an early onset autosomal-recessive PD gene, negatively regulates inflammatory responses of astrocytes and microglia by facilitating the interaction between STAT1 and its phosphatase, SHP-1 (Src-homology 2-domain containing protein tyrosine phosphatase-1). Astrocytes and microglia cultured from DJ-1-knockout (KO) mice exhibited increased expression of inflammatory mediators and phosphorylation levels of STAT1 (p-STAT1) in response to interferon-gamma (IFN-γ) compared to cells from wild-type (WT) mice. DJ-1 deficiency also attenuated IFN-γ-induced interactions of SHP-1 with p-STAT1 and STAT1, measured 1 and 12h after IFN-γ treatment, respectively. Subsequent experiments showed that DJ-1 directly interacts with SHP-1, p-STAT1, and STAT1. Notably, DJ-1 bound to SHP-1 independently of IFN-γ, whereas the interactions of DJ-1 with p-STAT1 and STAT1 were dependent on IFN-γ. Similar results were obtained in brain slice cultures, where IFN-γ induced much stronger STAT1 phosphorylation and inflammatory responses in KO slices than in WT slices. Moreover, IFN-γ treatment induced neuronal damage in KO slices. Collectively, these findings suggest that DJ-1 may function as a scaffold protein that facilitates SHP-1 interactions with p-STAT1 and STAT1, thereby preventing extensive and prolonged STAT1 activation. Thus, the loss of DJ-1 function may increase the risk of PD by enhancing brain inflammation.

A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson's disease gene knockout astrocytes.

Hydrogen sulfide (H2S) is a multifunctional signaling molecule that exerts neuroprotective effects in oxidative stress. In this article, we report a mitochondria-localized two-photon probe, SHS-M2, that can be excited by 750 nm femtosecond pulses and employed for ratiometric detection of H2S in live astrocytes and living brain slices using two-photon microscopy (TPM). SHS-M2 shows bright two-photon-excited fluorescence and a marked change in emission color from blue to yellow in response to H2S, low cytotoxicity, easy loading, and minimum interference from other biologically relevant species including reactive sulfur, oxygen, and nitrogen species, thereby allowing quantitative analysis of H2S levels. Molecular TPM imaging with SHS-M2 in astrocytes revealed that there is a correlation between the ratiometric analysis and expression levels of cystathionine ß-synthase (CBS), the major enzyme that catalyzes H2S production. In studies involving DJ-1, a Parkinson's disease (PD) gene, attenuated H2S production in comparison with wild-type controls was observed in DJ-1-knockout astrocytes and brain slices, where CBS expression was decreased. These findings demonstrate that reduced H2S levels in astrocytes may contribute to the development of PD and that SHS-M2 may be useful as a marker to detect a risk of neurodegenerative diseases, including PD.

The absence of coronary artery calcification does not rule out the presence of significant coronary artery disease in Asian patients with acute chest pain.

The absence of coronary artery calcification (CAC) has been used to as an indication to rule out significant coronary artery disease (CAD). However, diagnostic usefulness of 'zero calcium score criteria' as a decision-making strategy to rule out significant CAD as the etiology of acute chest pain has not been studied in depth, especially in Asian ethnicity. We prospectively enrolled 136 Korean patients (58% men, 56 ± 13 years) who presented to the emergency department (ED) with acute chest pain and non-diagnostic ECG. All patients underwent 64-slice CT for calcium scoring and coronary CT angiography (cCTA). We investigated the association of CAC with the presence of ≥50% CAD on cCTA and with a final diagnosis of an acute coronary syndrome (ACS). Ninety-two patients out of 136 (68%) did not show detectable CAC, and 14 out of these 92 without CAC (15%) had ≥50% CAD on cCTA. Sensitivity, specificity, positive predictive value and negative predictive value of zero calcium score criteria for the detection of ≥50% CAD were 0.66 (95% confidence interval, 0.50-0.80), 0.83 (0.74-0.90), 0.64 (0.48-0.77), 0.85 (0.75-0.91), respectively. Patients who had ≥50% CAD without detectable CAC were younger (P = 0.001), and had a higher prevalence of smoking (P = 0.048) as compared to patients with a degree of CAC. Most of the patients with ≥50% CAD of non-calcified plaque were younger than 60 years of age (79%, 11/14), however, 3 of them were older than 60 years of age. Forty-five patients (33%) were subsequently diagnosed as having ACS, and 38% (17/45) of them had no CAC. Zero calcium score did not necessarily guarantee the absence of significant CAD, even in patients older than 60 years, in Asian ethnicity presenting to the ED with chest pain.

Comparison of 2 point-of-care platelet function tests, VerifyNow Assay and Multiple Electrode Platelet Aggregometry, for predicting early clinical outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Various platelet function tests are currently used to measure responsiveness to antiplatelet therapy. We sought to compare 2 point-of-care platelet function tests, VerifyNow Assay (Accumetrics, San Diego, CA) and Multiple Electrode Platelet Aggregometry (MEA) (Dynabyte, Munich, Germany), for predicting early clinical outcomes after percutaneous coronary intervention. METHODS: Platelet reactivity in the arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously with the VerifyNow Assay and MEA in 222 patients undergoing percutaneous coronary intervention between August and October 2009. We investigated the correlations between the 2 tests and performed receiver operating characteristic curve analysis for major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), stroke, and target vessel revascularization, at 30 days. RESULTS: Major adverse cardiovascular events occurred in 19 patients (8.6%), including 14 patients with periprocedural MI and 5 patients with stroke. Correlations were weak between the 2 tests in the arachidonic acid-induced (Spearman r = 0.189, P = .006) and ADP-induced platelet reactivity (Spearman r = 0.390, P < .001). Although the VerifyNow P2Y12 Assay (Accumetrics) was able to predict periprocedural MI (area under the aggregation curve 0.680, P = .024) and 30-day MACE (area under the aggregation curve 0.649, P = .032), VerifyNow Aspirin Assay (Accumetrics), MEA ASPI test, and MEA ADP test failed to predict such clinical events. Hyporesponsiveness to clopidogrel based on the VerifyNow Assay was associated with about a 6-fold increased risk of MACE at 30 days. CONCLUSIONS: Hyporesponsiveness to clopidogrel measured by VerifyNow Assay was able to identify patients with dual antiplatelet therapy who were at higher risk for periprocedural MI and MACE at 30 days. Further randomized studies are required to validate the effectiveness of different platelet function tests for predicting long-term clinical outcomes.

Endothelial function is not changed during short-term withdrawal of thyroxine in patients with differentiated thyroid cancer and low cardiovascular risk.

PURPOSE: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. MATERIALS AND METHODS: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) and 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. RESULTS: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. CONCLUSION: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular risk.

Variation in atherosclerotic plaque composition according to increasing coronary artery calcium scores on computed tomography angiography.

Increasing coronary artery calcium scores (CACS) are independently associated with cardiac events. Recent advents in coronary computed tomography angiography (CCTA) have allowed us to better characterize individual plaque. Currently, it is unknown if higher CACS are likely to be associated with more calcified or mixed and heterogeneous plaque burden on CCTA. The study population consisted of 1,043 South Korean asymptomatic subjects (49 ± 10 years, 62% men) who underwent CCTA (64-slice MDCT). Plaques were classified on contrast-enhanced CCTA as non-calcified, mixed, and calcified on a per-segment basis according to the modified American Heart Association classification. The majority of the study participants had no coronary calcification (n = 866, 83%), whereas CACS> 0 was observed in 177 participants (17%). Only 40 (5%) participants in absence of CACS had exclusively non-calcified plaque, whereas 10 (1.2%) had significant coronary artery disease. With increasing CACS, study participants were more likely to have exclusively mixed or combination atherosclerotic plaques (P = 0.001). Among individuals with CACS 1-10, the prevalence of at least two coronary segments with mixed plaques was 4%, increasing up to 18 and 41% with CACS of 11-100 and >100. The respective prevalence of ≥2 coronary segments (calcified plaques) with increasing CACS were 6%, 16 and 26% (P = 0.01) and of non-calcified plaques were 6%, 6 and 11% (P = 0.71). In multivariable adjusted analyses, those with CACS >100 were 7.17 times (95% CI: 1.36-37.68) more likely to have ≥2 coronary segments with calcified plaque comparing with CACS 1-10. On the other hand the respective risk was higher for presence of ≥2 segments with mixed plaques (odds ratio: 15.81, 95% CI: 3.14-79.58). Absence of CAC is associated with a negligible presence of any atherosclerotic disease as detected by CCTA in asymptomatic population. A higher CACS is more likely to be associated with heterogeneous coronary plaque (combination of calcified, non-calcified, and mixed plaques), and appears to be more strongly associated with a higher burden of mixed plaque.

Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of occult coronary artery disease (CAD) with coronary computed tomography angiography (CTA) to characterize plaque composition and to evaluate the potential of this new technology to impact risk stratification in asymptomatic middle-aged subjects. BACKGROUND: There is a paucity of information regarding the role of CTA for the detection of occult CAD in asymptomatic individuals. METHODS: We consecutively enrolled 1,000 middle-aged asymptomatic subjects (age 50 +/- 9 years, 63% men) who underwent CTA (64-slice multidetector row computed tomography) as part of a general health evaluation. RESULTS: Atherosclerotic plaques were identified in 215 (22%, 2 +/- 1 segments/subject) individuals; 40 individuals (4%) had only noncalcified plaques. Fifty-two (5%) subjects had significant (>or=50%) diameter stenosis and 21 (2%) had severe (>or=75%) stenosis. Thirteen (25%) and 30 (58%) subjects with significant stenosis were classified into National Cholesterol Education Program low-risk and mild coronary calcification (coronary artery calcium scores <100), respectively. Midterm follow-up (17 +/- 2 months) revealed 15 cardiac events only in those with CAD on CTA: 1 unstable angina requiring hospital stay and 14 revascularization procedures. Most (87%) events occurred within 90 days of index CTA. CONCLUSIONS: The prevalence of occult CAD in apparently healthy individuals was not negligible, although their midterm prognosis was good. CTA has a potential to provide a better insight about the occult CAD in this population. However, on the basis of our results and considering present radiation exposure data, we cannot recommend that CTA be used as a screening tool for this population at this point.

Stent-related cardiac events after non-cardiac surgery: drug-eluting stent vs. bare metal stent.

For evaluation of post-operative stent associated cardiac events after drug-eluting stent (DES) implantation we analyzed data of 138 patients who underwent non-cardiac surgery after DES implantation and compared the data with those of 101 patients who underwent non-cardiac surgery after bare metal stent (BMS) implantation. Three patients (2.2%) in DES group developed post-operative cardiac events and none in BMS group (p=0.2). One patient died due to suspected stent thrombosis and the other two had myocardial infarction due to angiographically proven stent thrombosis. The time interval between stent implantation and surgery in those with cardiac events was 6, 264, and 367 days, respectively. Our data shows that peri-operative stent-related thrombotic complications can occur long after DES implantation and careful peri-operative monitoring for cardiac events is needed in patients receiving non-cardiac surgery after DES implantation.

NF-kappaB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis.

NF-kappaB promotes cell survival against external stress such as radiation. We examined whether NF-kappaB decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappaB p65 in VSMCs was confirmed by immunofluorescence. NF-kappaB decoy transfection resulted in inhibition of the radiation-induced NF-kappaB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappaB. By using MTT assay, NF-kappaB decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappaB decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappaB inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappaB decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappaB decoy transfection, P < 0.05). In addition, at 48 h, NF-kappaB decoy transfection dose dependently (10 microM vs. 20 microM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 microM sulfasalazine, a specific NF-kappaB inhibitor. These results indicate that NF-kappaB inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappaB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Thalidomide as a potent inhibitor of neointimal hyperplasia after balloon injury in rat carotid artery.

OBJECTIVE: Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. METHODS AND RESULTS: In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26+/-0.29 versus 0.35+/-0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-alpha) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-alpha, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856+/-213 versus 449+/-68 pg/mL on day 3, P=0.001; 129+/-34 versus 63+/-18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF-alpha levels and the severity of neointimal growth. CONCLUSIONS: We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.