Burden and frequency of viral testing of kidney and non-kidney transplant recipients.

Transplant patients are at risk of infections due to long-term immunosuppression contributing to morbidity and mortality in this population. Post-transplant testing guidelines were established to monitor and guide therapeutic interventions in transplant recipients. We hypothesize that there are gaps in adherence to the recommended frequency of laboratory testing in post-transplant patients. We analyzed national reference laboratory data to compare viral post-transplant infection (PTI) testing frequency with their respective published guidelines to understand patient uptake and compliance. We evaluated the ordering patterns, positivity rates, and frequency of molecular infectious disease tests (MIDTs). We included 345 patients with International Classification of Diseases (ICD)-10 codes for transplant (Z940-Z942, Z944, Z9481, Z9483, Z9484) with at least two tests (within 7 days) in January 2019 and at least one test in December 2020 to find patients in the post-transplant period. We analyzed two cohorts: kidney transplant recipients (KTRs; 40%) and non-KTR (60%) then followed them longitudinally for the study period. In KTR cohort, high-to-low proportion of ordered MIDT was blood BK virus (bBKV) followed by cytomegalovirus (CMV); in non-KTR cohort, CMV was followed by Epstein-Barr virus (EBV). KTR cohort positivity was highest for urine BK virus (uBKV; 58%) followed by EBV (46%), bBKV (40%), and CMV (31%). Non-KTR cohort positivity was highest for uBKV (64%), EBV (51%), CMV (30%), bBKV (8%), and adenovirus (7%). All patients were tested at progressively longer intervals from the date of the first post-transplant ICD-10-coded test. More than 40% of the KTR cohort were tested less frequently for EBV and bBKV, and more than 20% of the non-KTR cohort were tested for EBV less frequently than published guidelines 4 months after transplant. Despite regular testing, the results of MIDT testing for KTR and non-KTR patients in the post-transplant period are not aligned with published guidelines.IMPORTANCEGuidance for post-transplant infectious disease testing is established, however, for certain infections it allows for clinician discretion. This leads to transplant center policies developing their own testing/surveillance strategies based on their specific transplant patient population (kidney, stem cell, etc.). The Organ Procurement and Transplant Network (OPTN) has developed a strategic plan to improve and standardize the transplant process in the US to improve outcomes of living donors and recipients. Publishing national reference lab data on the testing frequency and its alignment with the recommended guidelines for post-transplant infectious diseases can inform patient uptake and compliance for these strategic OPTN efforts.

Risk Estimation of Severe COVID-19 Based on Initial Biomarker Assessment Across Racial and Ethnic Groups.

CONTEXT.­: Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis. OBJECTIVE.­: To develop predictive models of COVID-19 severity based on demographic, clinical, and laboratory data collected at initial patient contact after diagnosis of COVID-19. DESIGN.­: We studied demographic data and clinical laboratory biomarkers at time of diagnosis, using backward logistic regression modeling to determine severe and mild outcomes. We used deidentified data from 14 147 patients who were diagnosed with COVID-19 by polymerase chain reaction SARS-CoV-2 testing at Montefiore Health System, from March 2020 to September 2021. We generated models predicting severe disease (death or more than 90 hospital days) versus mild disease (alive and fewer than 2 hospital days), starting with 58 variables, by backward stepwise logistic regression. RESULTS.­: Of the 14 147 patients, including Whites, Blacks, and Hispanics, 2546 (18%) patients had severe outcomes and 3395 (24%) had mild outcomes. The final number of patients per model varied from 445 to 755 because not all patients had all available variables. Four models (inclusive, receiver operating characteristic, specific, and sensitive) were identified as proficient in predicting patient outcomes. The parameters that remained in all models were age, albumin, diastolic blood pressure, ferritin, lactic dehydrogenase, socioeconomic status, procalcitonin, B-type natriuretic peptide, and platelet count. CONCLUSIONS.­: These findings suggest that the biomarkers found within the specific and sensitive models would be most useful to health care providers on their initial severity evaluation of COVID-19.

Association between liver and chronic kidney disease on hemoglobin A1c concentrations.

INTRODUCTION: HbA1c is the gold standard for measuring long-range glycemic control in patients with type-2 diabetes mellitus. Conditions such as CKD or LD can lead to spurious HbA1c test results. There is conflicting literature about the relationship between HbA1c, LD, and CKD. METHODS: Results for HbA1c concentrations were retrieved from 2015- to 2019. We evaluated over 2,500 test results with LD and 20,000 results with CKD compared to over 21,000 test results without LD, iron deficiency anemia, or CKD. Patients were classified as having LD if they had high ALT and AST concentrations and classified as CKD, if they have abnormal serum creatinine and BUN or low eGFR based on age-based reference ranges. Kruskal-Wallis statistical analyses method was used to test whether the two populations followed the same distribution and significance. RESULTS: The median HbA1c concentration was 5.8% (40 mmol/l) among LD classified patients in both males and females vs. 5.4% (36 mmol/l) (P < 0.001) for females and 5.6% (38 mmol/l) (P < 0.001) for males without LD. A significant difference in median HbA1c concentrations were also observed between CKD samples (female: 5.7% (39 mmol/l), male: 6.0% (42 mmol/l)) and non-CKD samples (female: 5.4% (36 mmol/l), male: 5.6% (38 mmol/l)) (P < 0.001). Depending on the population's CKD stage, median concentrations of % HbA1c are increased from stage-1 through stage-4 and fell in Stage-5. CONCLUSION: Patients with high AST and ALT concentrations or CKD can have increased HbA1c concentrations compared to normal patients. When using HbA1c concentrations to monitor diabetes, healthcare professionals should consider LD or CKD status before making any therapeutic decisions.

Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations.

INTRODUCTION: HbA1c is a reliable biomarker for diagnosing and prognosis of diabetes, but many clinical scenarios and interfering factors can affect the test results. Any conditions that affect red cell turnover, such as iron-deficiency anemia (IDA), can lead to spurious HbA1c results. Reports on how IDA affects HbA1c concentrations are contradictory, and to understand better the association between HbA1c concentrations and IDA, we conducted a large-scale retrospective study. METHODS: Test results for HbA1c concentrations were retrieved from the years 2015-2019. We evaluated over 12,000 patients with IDA and 21,000 patients without IDA. Patients were classified as having IDA if samples with below the age-based ranges for serum iron, ferritin, or transferrin iron saturation and above age-based ranges for transferrin iron-binding capacity or transferrin concentrations. Kruskal-Wallis statistical analyses method was used to test whether the two samples follow the same distribution and significance. RESULTS: The median HbA1c concentration was 5.7% among IDA classified patients and 5.4% among normal samples (P < 0.001) for females. For males, the median HbA1c concentration was 6.0% among IDA classified patients and 5.6% among normal samples (P < 0.001). CONCLUSION: Patients classified as IDA can have increased HbA1c concentrations than patients without IDA. Clinicians should consider IDA status before making therapeutic decisions based on HbA1c concentrations.

Contributions of Glucose and Hemoglobin A1c Measurements in Diabetes Screening.

OBJECTIVES: Given the long-term consequences of untreated diabetes, patients benefit from timely diagnoses. Payer policies often recognize glucose but not hemoglobin A1c (HbA1c) for diabetes screening. This study evaluates the different information that glucose and HbA1c provide for diabetes screening. METHODS: We conducted a retrospective review of national clinical laboratory testing during 2020 when glucose and HbA1c were ordered for routine diabetes screening, excluding patients with known diabetes, out-of-range glucose, or metabolic syndrome. RESULTS: Of 15.47 million glucose and HbA1c tests ordered simultaneously, 672,467 (4.35%) met screening inclusion criteria; 116,585 (17.3%) were excluded because of diabetes-related conditions or the specimen was nonfasting, leaving 555,882 result pairs. More than 1 in 4 patients 60 years of age or older with glucose within range had an elevated HbA1c level. HbA1c claims were denied more often for Medicare beneficiaries (38,918/65,273 [59.6%]) than for other health plans combined (23,234/291,764 [8.0%]). CONCLUSIONS: Although many health plans do not cover HbA1c testing for diabetes screening, more than 1 in 4 glucose screening patients 60 years of age or older with an in-range glucose result had a concurrent elevated HbA1c result. Guideline developers and health plans should explicitly recognize that glucose and HbA1c provide complementary information and together offer improved clinical utility for diabetes screening.

Retrospective Performance Analyses of over Two Million U.S. QuantiFERON Blood Sample Results.

Both the QuantiFERON-TB Gold Plus (QFT-Plus) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) tests are interferon gamma (IFN-γ) release assays (IGRAs) intended to detect in vitro cell-mediated immune responses to Mycobacterium tuberculosis antigens. In this study, we retrospectively analyzed performance data for both the QFT-GIT and QFT-Plus test systems from over 2 million samples. QFT-Plus and QFT-GIT testing was performed as specified in the respective package inserts at 23 Quest Diagnostics sites. Blood specimens were collected from individuals in all 50 states from November 2018 through December 2019. Retrospective analyses compared the proportion of positive, indeterminate, and conversion/reversion results. The overall proportion of QFT-positive results was 7% for both the QFT-Plus and QFT-GIT. The proportion of positive results was highest for QFT-GIT (7.5%) followed by the heparin 1-tube QFT-Plus (7.2%); a lower proportion of positives was observed with the 4-tube (all four QFT tubes were used in blood collection) QFT-Plus (6.0%). The proportions of indeterminate results for the 1-tube (heparin-only tube collection) and 4-tube QFT-Plus methods were less than 1% and 4%, respectively. This study indicates a higher proportion of positive results for M. tuberculosis than data from other studies. Additionally, the proportion of indeterminate QFT results were markedly lower when the sample was transported in one lithium-heparin tube instead of direct inoculation into 4 QFT-Plus tubes at the site of blood collection. IMPORTANCE In this study, we retrospectively analyzed results from both the QFT-GIT and QFT-Plus test systems from over 2 million blood specimens. The variables analyzed were (i) QFT positivity rates among various U.S. populations, (ii) indeterminate rates among various types of blood draws and how often an indeterminate result was resolved within 30 days after the initial draw, and (iii) the association of TB1 and TB2 antigen tubes with IGRA reversion and conversion events from serial QFT testing. This is, to our knowledge, the largest QFT study representing patients from an extensive geographic coverage across the United States and U.S. territories.

SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ≥55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.

Measurement of Cortisol and Testosterone in Athletes: Accuracy of Liquid Chromatography-Tandem Mass Spectrometry Assays for Cortisol and Testosterone Measurement in Whole-Blood Microspecimens.

Fragala, MS, Goldman, SM, Goldman, MM, Bi, C, Colletti, JD, Arent, SM, Walker, AJ, and Clarke, NJ. Measurement of cortisol and testosterone in athletes: Accuracy of LC-MS/MS assays for cortisol and testosterone measurement in whole-blood microspecimens. J Strength Cond Res 32(9): 2425-2434, 2018-Biomarker monitoring provides insight into athletes' training tolerance but is limited by the need for office-based specimen collection. To facilitate self-collection during training, we developed liquid chromatography-tandem mass spectrometry-based tests that measure circulating total cortisol and testosterone using a finger stick volumetric absorptive microsampler. Here, we describe the analytical validation of these tests. Forty-six Division I athletes (18-22 years, 30 women, 16 men) provided a 20-µL finger stick microspecimen and a 5-ml venous blood specimen from the forearm; the venous blood sample was analyzed using both normal volume serum analysis and analysis of dried whole blood (from the microsampler). Liquid chromatography-tandem mass spectrometry on standard serum specimens obtained by venipuncture yielded total cortisol levels of 26.2 ± 11.6 µg·dl (women and men), and total testosterone levels of 37 ± 17 ng·dl in women and 564 ± 171 ng·dl in men. Analytical measurement ranges of the microspecimen assay were 0.3-440 µg·dl (CV <9%) for cortisol and 15 to 20,000 ng·dl (CV <9%) for testosterone. Deming regression and Pearson correlation indicated good test accuracy for the microspecimen tests compared with venipuncture tests for cortisol (y = 0.98x + 1.34, 95% CI of slope = 0.83-1.14; r = 0.92, p < 0.0001) and testosterone (y = 1.06x - 0.01, 95% CI of slope = 0.99-1.14; r = 0.99, p < 0.0001). Similarly, high agreement was observed between finger stick and venous microspecimens for cortisol (y = 1.00x + 0.65, 95% CI of slope = 0.9-1.11; r = 0.96, p < 0.001) and testosterone (y = 0.97x + 2.75, 95% CI of slope = 0.9-1.03; r = 0.99, p < 0.001). These findings suggest the viability of finger stick collection whole-blood microspecimens for assessment of total cortisol and testosterone in athletes.

Associations of aerobic and strength exercise with clinical laboratory test values.

OBJECTIVES: Physical exercise may affect levels of blood-based biomarkers. However, exercise status is seldom considered in the interpretation of laboratory results. This study reports the associations between habitual exercise participation and clinical laboratory test results. METHODS: The effects of days per week of aerobic and strength exercise participation on laboratory test results for 26 biomarkers in young adults aged 18 to 34 years (n = 80,111) were evaluated using percentile distribution analyses and multivariate regression. RESULTS: In both men and women, more days per week of either aerobic or strength exercise were significantly associated with lower levels of glucose, hemoglobin A1c, LDL cholesterol, total cholesterol, triglycerides, estimated glomerular filtration rate, globulin, and C-reactive protein, and significantly higher levels of HDL cholesterol, creatinine, iron, and percent saturation (all p < .05). Type of exercise or gender influenced the observed relationships with exercise frequency for total cholesterol, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, uric acid, bilirubin, and iron binding capacity. CONCLUSIONS: Physical exercise shifted the distribution of results into the direction suggestive of better health. Reported relationships may help clinicians and patients to better understand and interpret laboratory results in athletic populations and possibly re-evaluate interpretation of reference intervals for physically active populations.

Assessing the Impact of Analytical Error on Perceived Disease Severity.

CONTEXT: The perception of the severity of disease from laboratory results assumes that the results are free of analytical error; however, analytical error creates a spread of results into a band and thus a range of perceived disease severity. OBJECTIVE: To assess the impact of analytical errors by calculating the change in perceived disease severity, represented by the hazard ratio, using non-high-density lipoprotein (nonHDL) cholesterol as an example. DESIGN: We transformed nonHDL values into ranges using the assumed total allowable errors for total cholesterol (9%) and high-density lipoprotein cholesterol (13%). Using a previously determined relationship between the hazard ratio and nonHDL, we calculated a range of hazard ratios for specified nonHDL concentrations affected by analytical error. RESULTS: Analytical error, within allowable limits, created a band of values of nonHDL, with a width spanning 30 to 70 mg/dL (0.78-1.81 mmol/L), depending on the cholesterol and high-density lipoprotein cholesterol concentrations. Hazard ratios ranged from 1.0 to 2.9, a 16% to 50% error. Increased bias widens this range and decreased bias narrows it. CONCLUSIONS: Error-transformed results produce a spread of values that straddle the various cutoffs for nonHDL. The range of the hazard ratio obscures the meaning of results, because the spread of ratios at different cutoffs overlap. The magnitude of the perceived hazard ratio error exceeds that for the allowable analytical error, and significantly impacts the perceived cardiovascular disease risk. Evaluating the error in the perceived severity (eg, hazard ratio) provides a new way to assess the impact of analytical error.

Temporal relationship between vitamin D status and parathyroid hormone in the United States.

BACKGROUND: Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season. OBJECTIVE: Characterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels. METHOD: We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32-40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL). FINDINGS: Seasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2. INTERPRETATION: 25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care.

EphA activation overrides the presynaptic actions of BDNF.

The adult pattern of neural connectivity is shaped by repulsive and attractive factors, many of which are modulated by activity. Although much is known about the actions of these factors when studied in isolation, little is known about how they interact. To address this question, we examined the effects of sequential or coapplication of brain-derived neurotrophic factor (BDNF) and Fc-conjugated ephrin-A5 or EphA5 in cultured embryonic hippocampal neurons. BDNF promotes neurite outgrowth and synapse formation, and when applied acutely, it elicits an increase in ongoing synaptic activity. Members of the ephrin family of ligands and receptors can be repulsive and prevent formation of synaptic contacts. Acute exposure to either ephrin-A5-Fc or EphA5-Fc transiently enhanced synaptic activity when applied alone, but when applied prior to BDNF, they dramatically reduced the electrophysiological effects of the neurotrophin. Conversely, BDNF had no effect on subsequently applied ephrin-A5-Fc or EphA5-Fc. Consistent with this, ephrin-A5-Fc also prevented BDNF-induced activation of p42/44 MAPK. The effect of ephrin-A5-Fc appears to be presynaptic, as it prevented the BDNF-induced increase in spontaneous miniature postsynaptic current frequency, whereas EphA5-Fc did not. These results suggest that these factors can be categorized differently, with the contact-mediated activation of EphA receptors by ephrin-A5 overriding the diffusion-mediated effect of BDNF.

BDNF modulation of NMDA receptors is activity dependent.

Brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic transmission, is known to influence associative synaptic plasticity and refinement of neural connectivity. We now show that BDNF modulation of glutamate currents in hippocampal neurons exhibits the additional property of use dependence, a postsynaptic mechanism resulting in selective modulation of active channels. We demonstrate selectivity by varying the repetition rate of iontophoretically applied glutamate pulses during BDNF exposure. During relatively high-frequency glutamate pulses (0.1 Hz), BDNF application elicited a doubling of the glutamate current. During low-frequency pulses (0.0033 Hz), however, BDNF evoked a dramatically diminished response. This effect was apparently mediated by calcium because manipulations that prevented elevation of intracellular calcium largely eliminated the action of BDNF on glutamate currents. To confirm N-methyl-D-aspartate (NMDA) receptor involvement and assess spatial requirements, we made cell-attached single-channel recordings from somatic NMDA receptors. Inclusion of calcium in the pipette was sufficient to produce enhancement of channel activity by BDNF. Substitution of EGTA for calcium prevented BDNF effects. We conclude that BDNF modulation of postsynaptic NMDA receptors requires concurrent neuronal activity potentially conferring synaptic specificity on the neurotrophin's actions.

Functional differentiation of a clone resembling embryonic cortical interneuron progenitors.

We have generated clones (L2.3 and RG3.6) of neural progenitors with radial glial properties from rat E14.5 cortex that differentiate into astrocytes, neurons, and oligodendrocytes. Here, we describe a different clone (L2.2) that gives rise exclusively to neurons, but not to glia. Neuronal differentiation of L2.2 cells was inhibited by bone morphogenic protein 2 (BMP2) and enhanced by Sonic Hedgehog (SHH) similar to cortical interneuron progenitors. Compared with L2.3, differentiating L2.2 cells expressed significantly higher levels of mRNAs for glutamate decarboxylases (GADs), DLX transcription factors, calretinin, calbindin, neuropeptide Y (NPY), and somatostatin. Increased levels of DLX-2, GADs, and calretinin proteins were confirmed upon differentiation. L2.2 cells differentiated into neurons that fired action potentials in vitro, and their electrophysiological differentiation was accelerated and more complete when cocultured with developing astroglial cells but not with conditioned medium from these cells. The combined results suggest that clone L2.2 resembles GABAergic interneuron progenitors in the developing forebrain.

Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a key regulator of hippocampal synaptic plasticity in the developing and adult nervous system. It can be released from pyramidal neuron dendrites in an activity-dependent manner and has therefore been suggested to serve as a signal that provides the retrograde intercellular communication necessary for Hebbian plasticity and hippocampal-dependent learning. Although much has been learned about BDNF function by field stimulation of hippocampal neurons, it is not known whether moderate action potential-independent depolarization of single cells is capable of releasing sufficient BDNF to influence transmission at individual synapses. In this study, we show directly at the single-cell level that such modulation can occur. By using K-252a, anti-BDNF antibody, and interruption of regulated release, we confirm a model in which postsynaptic depolarization elicits calcium-dependent release of BDNF that diffuses retrogradely and enhances presynaptic transmitter release.

The effect of early auditory deprivation on the age-dependent expression pattern of NR2B mRNA in rat auditory cortex.

NMDA receptors have been well shown to be involved in neuronal plasticity. In order to understand the role of NR2B subtype NMDA receptors in auditory function development, the present study investigated the effect of early auditory deprivation on the expression of NR2B mRNA in rat auditory cortex (AC) during postnatal development. For normal rats, the NR2B mRNA expression was highest at birth (postnatal day 1 [P1]) and declined rapidly to low level during adulthood. However, during the critical period of rat auditory development (two to three weeks after birth), there was a transient NR2B expression peak on postnatal day 21 (P21). For the auditory-deprived rats, the general declining trend of NR2B mRNA expression from birth to adult was similar to that observed in the normal group, whereas the expression level from P15 to P27 was significantly lower than normal and the transient peak on P21 disappeared. In both groups, the distribution pattern of NR2B mRNA-positive neurons was also examined in various layers and dorsal, medial and ventral subdistricts of AC. There is no significant effect on the spatial expression of the NR2B mRNA in the AC between normal and deprived group. Our results indicated that the early auditory deprivation decreased the expression levels of NR2B mRNA in AC during the critical period of rat auditory development, suggesting that NR2B plays an important role in the developmental plasticity of auditory function in rats.