Out of the Laboratory and Into the Field: Validation of Portable Cell Culture Protocols.

OBJECTIVE: Field-based research on inflammation and health is typically limited to baseline measures of circulating cytokines or acute-phase proteins, whereas laboratory-based studies can pursue a more dynamic approach with ex vivo cell culture methods. The laboratory infrastructure required for culturing leukocytes limits application in community-based settings, which in turn limits scientific understandings of how psychosocial, behavioral, and contextual factors influence the regulation of inflammation. We aim to address this gap by validating two "field-friendly" cell culture protocols, one using a small volume of venous whole blood and another using finger-stick capillary whole blood. METHODS: We evaluated the performance of both protocols against a standard laboratory-based protocol using matched venous and capillary blood samples collected from young adults (n = 24). Samples were incubated with lipopolysaccharide and hydrocortisone, and the production of proinflammatory cytokines interleukin 1ß, interleukin 6, and tumor necrosis factor α was measured in response. RESULTS: Comparisons indicate a high level of agreement in responses across the protocols and culture conditions. The overall correlation in results was 0.88 between the standard and small-volume protocols and 0.86 between the standard and capillary blood protocols. Repeatability for the small-volume and capillary blood protocols was high, with mean coefficients of variation across five replicates of 6.2% and 5.4%, respectively. CONCLUSIONS: These results demonstrate the feasibility of culturing cells and quantifying the inflammatory response to challenge outside the laboratory, with a wide range of potential applications in biobehavioral research in community-based and remote field settings.

Effects of social support in an academic context on low-grade inflammation in high school students.

Bolstering academic motivation is a high priority in school settings, but some evidence suggests this could take a toll on students' physical health. To address this, this study compared the effects of an experimental manipulation of academic motivation alone (AM) to academic motivation enhanced with social support (SS + AM) on markers of inflammation in a sample of 80 high school 9th graders. Outcomes included low-grade inflammation: C-reactive protein (CRP) and interleukin-6 (IL-6); a motivation measure; and grade point average (GPA), taken at baseline and follow-up (beginning and end of school year, respectively). Students in the SS + AM condition had lower levels of inflammation at follow-up (covarying baseline levels) compared to those in the AM condition. The two groups were equivalent on motivation and GPA at follow-up. This preliminary study suggests that incorporating social support into academic motivation programs has the potential to benefit inflammatory markers in young people while allowing them to maintain positive academic outcomes.

Longer Sleep Duration and Endothelial Cell Health Among a Multiethnic Sample of Adolescents.

OBJECTIVE: Adverse endothelial cell health, an early pathogenic process underlying atherosclerosis and cardiovascular disease, is evident in childhood and adolescence. Sleep duration, a modifiable cardiovascular health behavior, may be an important cardiovascular disease prevention target that may affect endothelial cell health. We examined the associations of longer sleep duration with endothelial cell injury among youth. METHODS: In a multiethnic sample of 235 children (63.0% female, mean age = 13.9 years), we conducted multivariable linear regressions to test the cross-sectional association of sleep duration and circulating levels of endothelial cell-derived microparticles (EMPs), phenotypic for endothelial cell activation and apoptosis (CD62E+ EMPs, CD31+/CD42b- EMPs, and CD31+/Annexin V+ EMPs). Sleep duration and EMPs were both treated as continuous variables. Models were adjusted for age, sex, race, pubertal status, household economic resources, and waist circumference. RESULTS: Overall, 69.2% had short sleep duration (<8 hours of sleep per night). Longer sleep duration was significantly associated with lower levels of CD62E+ EMPs and CD31+/CD42b- EMPs. A 60-minute increase in sleep duration was associated with an 8.40 (95% confidence interval = -205.20 to -1.80, p = .046) decrease in CD62E+ EMPs and a 9.00 (95% confidence interval = -153.60 to -9.60, p = .027) decrease in CD31+/CD42b- EMPs. Sleep duration was not associated with CD31+/Annexin V+ EMPs. CONCLUSIONS: Our results support the hypothesis that sleeping longer has beneficial effects on endothelial cell health during childhood. Primordial prevention efforts might incorporate sleep extension to offset cardiovascular risk in youth.

The costs of high self-control in Black and Latino youth with asthma: Divergence of mental health and inflammatory profiles.

Emerging evidence in psychology suggests a paradox whereby high levels of self-control when striving for academic success among minority youth can have physical health costs. This study tested the skin-deep resilience hypothesis in asthma- whether minority youth who are striving hard to succeed academically experience good psychological outcomes but poor asthma outcomes. Youth physician-diagnosed with asthma (N = 276, M age = 12.99; 155 = White, 121 = Black/Latino) completed interviews about school stress and a self-control questionnaire. Outcomes included mental health (anxiety/depression) and ex-vivo immunologic processes relevant to asthma (lymphocyte Th-1 and Th-2 cytokine production, and sensitivity to glucocorticoid inhibition). Physician contacts were tracked over a one-year follow-up. For minority youth experiencing high levels of school stress, greater self-control was associated with fewer mental health symptoms (beta = -0.20, p < .05), but worse asthma inflammatory profiles (larger Th-1 and Th-2 cytokine responses, lower sensitivity to glucocorticoid inhibition), and more frequent physician contacts during the one-year follow-up (beta's ranging from 0.22 to 0.43, p's < .05). These patterns were not evident in White youth. In minority youth struggling with school, high levels of self-control are detrimental to asthma inflammatory profiles and clinical outcomes. This suggests the need for health monitoring to be incorporated into academic programs to ensure that 'overcoming the odds' does not lead to heightened health risks in minority youth.

Consistency matters: Consistency in the timing and quality of daily interactions between parents and adolescents predicts production of proinflammatory cytokines in youths.

The current study examined whether consistency in day-to-day interactions between children and parents related to inflammatory cytokine production in youths. One hundred twenty-three parents recorded the daily quality of interactions and timing of leisure activities with their adolescent children for 2 weeks, and the degree of variability in those ratings was calculated. One year later, the production of proinflammatory cytokines in youths' blood was measured in response to in vitro exposure to lipopolysaccharide (a bacterial product). The results indicate that greater variability in parent-child relationship quality related to greater stimulated proinflammatory cytokine production in youths, above and beyond overall relationship quality. Greater variability in the timing of parent-child leisure activities also predicted greater stimulated proinflammatory cytokine production in youths, regardless of the frequency of interactions. In sum, consistency in both the affective and temporal aspects of parent-child relationships may contribute to inflammatory processes in youth.

Maternal socioeconomic disadvantage is associated with transcriptional indications of greater immune activation and slower tissue maturation in placental biopsies and newborn cord blood.

Children from economically disadvantaged families experience worse cognitive, psychiatric, and medical outcomes compared to more affluent youth. Preclinical models suggest some of the adverse influence of disadvantage could be transmitted during gestation via maternal immune activation, but this hypothesis has not been tested in humans. It also remains unclear whether prenatal interventions can mitigate such effects. To fill these gaps, we conducted two studies. Study 1 characterized the socioeconomic conditions of 79 women during pregnancy. At delivery, placenta biopsies and umbilical blood were collected for transcriptional profiling. Maternal disadvantage was associated with a transcriptional profile indicative of higher immune activation and slower fetal maturation, particularly in pathways related to brain, heart, and immune development. Cord blood cells of disadvantaged newborns also showed indications of immaturity, as reflected in down-regulation of pathways that coordinate myeloid cell development. These associations were independent of fetal sex, and characteristics of mothers (age, race, adiposity, diabetes, pre-eclampsia) and babies (delivery method, gestational age). Study 2 performed the same transcriptional analyses in specimens from 20 women participating in CenteringPregnancy, a group-based psychosocial intervention, and 20 women in traditional prenatal care. In both placenta biopsies and cord blood, women in CenteringPregnancy showed up-regulation of transcripts found in Study 1 to be most down-regulated in conjunction with disadvantage. Collectively, these results suggest socioeconomic disparities in placental biology are evident at birth, and provide clues about the mechanistic origins of health disparities. They also suggest the possibility that psychosocial interventions could have mitigating influences.

Dimensions of Socioeconomic Status and Childhood Asthma Outcomes: Evidence for Distinct Behavioral and Biological Associations.

OBJECTIVES: The objective of this study was to investigate 2 key dimensions of socioeconomic status (SES)-prestige and resources-and their associations with immune, behavioral, and clinical outcomes in childhood asthma. METHODS: Children ages 9 to 17 years with a physician's diagnosis of asthma (N = 150), and one of their parents participated in this study. Children and parents completed interviews and questionnaires about SES (prestige = parent education; resources = family assets), environmental exposures, and clinical asthma measures. Spirometry was conducted to assess children's pulmonary function, and blood was collected to measure cytokine production in response to nonspecific stimulation, allergen-specific stimulation, and microbial stimulation. RESULTS: Higher scores on both dimensions of childhood SES were associated with better clinical outcomes in children (ß's from |.18 to .27|, p values < .05). Higher prestige, but not resources, was associated with better home environment control behaviors and less exposure to smoke (ß's from |.21 to .22|, p values < .05). Higher resources, but not prestige, was associated with more favorable immune regulation, as manifest in smaller peripheral blood mononuclear cell (PBMC) TH1 and TH2 cytokine responses (ß's from -.18 to -.19; p values < .05), and smaller proinflammatory cytokine responses (ß = -.19; p < .05) after ex vivo stimulation. Higher resources also were associated with more sensitivity to glucocorticoid inhibition of TH1 and TH2 cytokine production (ß's from -.18 to -.22; p values < .05). CONCLUSIONS: These results suggest that prestige and resources in childhood family environments have different implications for behavioral and immunological processes relevant to childhood asthma. They also suggest that childhood SES relates to multiple aspects of immunologic regulation of relevance to the pathophysiology of asthma.

Acute Heart Failure Due to Aluminum Phosphide Poisoning.

Aluminum phosphide (ALP) is a pesticide agent and infrequent culprit of accidental poisoning. We present a case of severe reversible cardiomyopathy and left ventricular apical thrombus in a patient who worked as an exterminator and had ALP poisoning.

Resting-State Functional Connectivity of the Central Executive Network Moderates the Relationship Between Neighborhood Violence and Proinflammatory Phenotype in Children.

BACKGROUND: Neighborhood violence increases children's risk for a variety of health problems. Yet, little is known about biological pathways involved or neural mechanisms that might render children more or less vulnerable. Here, we address these questions by considering whether neighborhood violence is associated with the expression of a proinflammatory phenotype and whether this relationship is moderated by resting-state functional connectivity (rsFC) of the central executive network (CEN). METHODS: The study involved 217 children (13.9 years old; 66.4% female; 36.9% Black; 30.9% Latinx), enrolled in eighth grade and reassessed 2 years later. At time 1, geocoding was used to estimate murder frequency in children's neighborhoods, and functional magnetic resonance imaging was used to characterize CEN rsFC. At both visits, children gave antecubital blood for ex vivo studies, where leukocytes were incubated with stimulators and inhibitors of inflammation, and cytokine production was measured. RESULTS: Consistent with our hypotheses, the relationship between neighborhood murder and inflammatory activity was moderated by CEN rsFC. Among children with lower rsFC, neighborhood violence covaried with a proinflammatory phenotype, reflected in larger cytokine responses to triggering stimuli and lower sensitivity to inhibitory agents. These associations were generally not apparent for children with higher rsFC, although occasionally they ran in the opposite direction. The same patterns were apparent 2 years later. CONCLUSIONS: These results advance the understanding of neighborhood violence and its relationship with processes involved in the initiation and resolution of inflammation. They also deepen understanding of variability in children's immunologic responses to stress and suggest that the CEN may be a neurobiological contributor to resilience.

Community violence and cellular and cytokine indicators of inflammation in adolescents.

Neighborhood violence is associated with a range of health consequences but little is known about the biological processes involved. Research in disease pathogenesis has identified low-grade inflammation as a process that, beginning in the first decades of life, is both induced by chronic stress and a contributor to multiple cardiometabolic diseases that present throughout the lifecourse. Previous research has examined whether neighborhood violence is associated with inflammatory biomarkers, but has been limited to cytokine indicators of inflammation. In a sample of adolescents (n = 203) residing in Chicago, we tested cross-sectional associations between neighborhood violence and cellular and cytokine indicators of inflammation. Neighborhood-level violence was measured in multiple ways (as murder rates of Census block groups and as the sum of homicides within 1 and ½ mile zones) in the areas surrounding where youth lived and attended school. At the individual level, violence exposure was measured by self-report (direct victimization, witnessing violence, and/or victimization of family or friends in the past year). Adolescents residing in high-violence neighborhoods evidenced higher numbers of pro-inflammatory classical (CD14++CD16-) monocytes relative to those in less violent neighborhoods. In contrast, neighborhood-level violence was not consistently associated with cytokine levels across different model specifications. Self-reported violence exposure was also not consistently associated with inflammatory biomarkers. Neighborhood-level violence and self-reported violence exposure interacted, such that the positive association between neighborhood-level violence and classical monocytes was observed only among adolescents who reported being exposed to violence. Associations were largely specific to the neighborhoods in which youth lived as opposed to those in which they attended school. Findings provide the first evidence that youth residing in high-violence neighborhoods show mobilization of classical monocytes, suggesting a pro-inflammatory mechanism through which contextual stressors such as neighborhood violence may compromise health.

Familism and inflammatory processes in African American, Latino, and White youth.

OBJECTIVE: African Americans and Latinos make up the two largest minority groups in the United States, and compared with Whites, these ethnic minority groups face disproportionate risk for certain physical health problems. However, factors that may protect these groups against early risk for poor health are not entirely understood. Familism, which emphasizes family interdependence and commitment, and is more prevalent among Latino and African American families, may be one such factor. The current study examined whether values and behaviors related to familism were differentially associated with inflammatory processes among White, African American, and Latino youth. METHOD: Participants were 257 youth who completed measures of familism values and behaviors and whose parents reported on their ethnicity. Participants also provided blood samples for the assessment of proinflammatory cytokine responses to bacterial challenge and of sensitivity to anti-inflammatory features of cortisol and interleukin (IL)-10. RESULTS: Significant familism values and behaviors by ethnicity interactions were observed. For Latino and African American youth but not for White youth, more familism values were associated with greater sensitivity to IL-10. Additionally, for African American youth, more familism behaviors were associated with decreased cytokine responses to bacterial challenge and greater sensitivity to cortisol and IL-10. By contrast, familism behaviors were associated with lower sensitivity to cortisol in White youth and were not associated with any inflammatory outcomes in Latino youth. CONCLUSION: This pattern of findings suggests that for African American youth and to some extent for Latino youth, familism values and behaviors may be protective against the elevated risk for poor health they face. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk Stratification in Smokers.

OBJECTIVES: This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE). BACKGROUND: The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers. CAC can be obtained from these low-dose scans. The incremental utility of CAC for ASCVD risk stratification remains unclear in this high-risk group. METHODS: Of 6,814 MESA (Multi-Ethnic Study of Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476 former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional hazards, area under the curve, and net reclassification improvement (NRI) analyses were used to assess the association between PCE and/or CAC and incident ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial infarction, or fatal or nonfatal stroke. RESULTS: Smokers had a mean age of 62.1 years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One SD increase in the PCE 10-year risk was associated with a 68% increase risk for ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to 1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models. The C-statistic of the PCE for ASCVD was higher in all smokers compared with LCSE smokers (0.693 vs. 0.545). CAC significantly improved the C-statistics of the PCE in all smokers but not in LCSE smokers. The event and nonevent net reclassification improvements for all smokers and LCSE smokers were 0.018 and -0.126 versus 0.16 and -0.196, respectively. CONCLUSIONS: In this well-characterized, multiethnic U.S. cohort, CAC was predictive of ASCVD in all smokers and in LCSE smokers but modestly improved discrimination over and beyond the PCE. However, 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had an ASCVD event during follow-up.

Decline in age-dependent, MK801-induced injury coincides with developmental switch in parvalbumin expression: somatosensory and motor cortex.

MK801-induced activation of caspase-3 is developmentally regulated, peaking at postnatal day (P) 7 and decreasing with increasing postnatal age thereafter. Further, at P7, cells displaying activation of caspase-3 lack expression of calcium binding proteins (CaBPs). To further explore this relationship, we investigated postnatal expression of calbindin (CB), calretinin (CR) and parvalbumin (PV) in two brain regions susceptible to MK801-induced injury, the somatosensory cortex (S1) and layer II/III of motor cortex (M1/M2). Expression of CB and especially PV was low to absent prior to P7 but substantially increased from P7 through to P21 and adulthood. In contrast, CR expression was more variable at early developmental ages, stabilized to lower levels after P7 and showed a marked decline by P21. The results suggest that not only does calcium buffering capacity increase developmentally but also acquisition of enhanced buffering may be one mechanism by which neurons survive agent-induced alterations in calcium homeostasis.

Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status.

AIM: There are marked socioeconomic disparities in pediatric asthma control, but the molecular origins of these disparities are not well understood. To fill this gap, we performed genome-wide expression profiling of monocytes and T-helper cells from pediatric asthma patients of lower and higher socioeconomic status (SES). METHOD: Ninety-nine children with asthma participated in a cross-sectional assessment. Out of which 87% were atopic, and most had disease of mild (54%) or moderate (29%) severity. Children were from lower-SES (n = 49; household income <$50 000) or higher-SES (n = 50; household income >$140 000) families. Peripheral blood monocytes and T-helper cells were isolated for genome-wide expression profiling of mRNA. RESULTS: Lower-SES children had worse asthma quality of life relative to higher-SES children, by both their own and their parents' reports. Although the groups had similar disease severity and potential confounds were controlled, their transcriptional profiles differed notably. The monocytes of lower-SES children showed transcriptional indications of up-regulated anti-microbial and pro-inflammatory activity. The T-helper cells of lower-SES children also had comparatively reduced expression of genes encoding γ-interferon and tumor necrosis factor-α, cytokines that orchestrate Type 1 responses. They also showed up-regulated activity of transcription factors that polarize cells towards Type 2 responses and promote Th17 cell maturation. CONCLUSION: Collectively, these patterns implicate pro-inflammatory monocytes and Type 2 cytokine activity as mechanisms contributing to worse asthma control among lower-SES children.

Close relationship qualities and maternal peripheral inflammation during pregnancy.

OBJECTIVE: Close relationships are associated with pregnancy outcomes, but little is known about the mechanisms involved. This paper examines whether quality of women's close relationships, specifically with romantic partner (RP) and closest friend or family member (CF), is associated with inflammatory biomarkers during the third trimester of pregnancy. METHODS: 90 pregnant women were assessed during the second and third trimester. At both visits they completed self-reports describing the positive and negative aspects of their RP and CF relationships. Peripheral blood was collected during these visits, and used to measure systemic levels of cytokines, including IFNγ, IL10, IL6, IL8 and IL13. An index of inflammatory regulation, as reflected by the ratio of IL6:IL10, was also computed. RESULTS: Positive (e.g. support, intimacy) and negative (e.g. conflict) aspects of the RP relationship interacted to predict third trimester cytokine values. Specifically, RP relationships relatively low in both positive and negative aspects were associated with lower third trimester anti-inflammatory (IL10, IL13) and anti-viral (IFNγ) cytokines, and a higher IL6:IL10 ratio, controlling for second trimester levels. These associations were independent of demographics, gestational age, weeks between assessment, parity, pre-pregnancy body mass index, maternal stress, distress, depressed mood and RP cohabitation. CF relationship aspects were not associated with inflammatory markers. CONCLUSIONS: RP relationships relatively low in both positive, e.g. support and intimacy, and negative, e.g. conflict, aspects were associated with a less anti- and more pro-inflammatory cytokine profile during the third trimester. These findings have implications for understanding the associations amongst close relationships, inflammation, and potentially pregnancy outcomes.

Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood.

PROBLEM: Maternal inflammation undergoes adaptations during pregnancy, and excessive inflammation has been associated with adverse outcomes. One mechanism may be maternal inflammation transmission to the fetal compartment. Links between maternal pregnancy inflammation and fetal inflammation are poorly characterized. METHOD: Principal components analysis was used to extract underlying inflammation components across cytokines (IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α) in two pregnancy cohorts (SPAH N=87, MOMS N=539) assessed during the second and third trimesters. Links between maternal inflammation over pregnancy and fetal (cord blood) inflammation were assessed. RESULTS: Substantial cytokine rank-order stability was observed in both cohorts, ß's range .47-.96, P's <.001. Two consistent inflammatory components were extracted: a pro-inflammatory (IL-10, IL-6, IL-8, TNF-α, IFN-γ) component and anti-inflammatory (IL-13) component. Higher maternal pro-inflammatory and lower anti-inflammatory indices during pregnancy were associated with higher cord blood inflammation, P's>.04. CONCLUSION: Maternal inflammation indices over pregnancy were associated with inflammation in cord blood at birth. Results have implications for understanding pregnancy inflammatory processes and how maternal inflammation may be transmitted to fetal circulation.

Effects of long-term fertilization of forest soils on potential nitrification and on the abundance and community structure of ammonia oxidizers and nitrite oxidizers.

Forest fertilization in British Columbia is increasing, to alleviate timber shortfalls resulting from the mountain pine beetle epidemic. However, fertilization effects on soil microbial communities, and consequently ecosystem processes, are poorly understood. Fertilization has contrasting effects on ammonia-oxidizing bacteria and archaea (AOB and AOA) in grassland and agricultural ecosystems, but there are no studies on AOB and AOA in forests. We assessed the effect of periodic (6-yearly application 200 kg N ha⁻¹) and annual (c. 75 kg N ha⁻¹) fertilization of lodgepole pine and spruce stands at five long-term maximum productivity sites on potential nitrification (PN), and the abundance and diversity of AOB, AOA and Nitrobacter and Nitrospira-like nitrite-oxidizing bacteria (NOB). Fertilization increased AOB and Nitrobacter-like NOB abundances at some sites, but did not influence AOA and Nitrospira-like NOB abundances. AOB and Nitrobacter-like NOB abundances were correlated with PN and soil nitrate concentration; no such correlations were observed for AOA and Nitrospira-like NOB. Autotrophic nitrification dominated (55­97%) in these forests and PN rates were enhanced for up to 2 years following periodic fertilization. More changes in community composition between control and fertilized plots were observed for AOB and Nitrobacter-like NOB than AOA. We conclude that fertilization causes rapid shifts in the structure of AOB and Nitrobacter-like NOB communities that dominate nitrification in these forests.

Decline in age-dependent, MK801-induced injury coincides with developmental switch in parvalbumin expression: cingulate and retrosplenial cortex.

Age-dependent, MK801-induced, activated caspase-3 expression in the postnatal brain is generally not observed in neurons expressing calcium-binding proteins (CaBPs), suggesting that apoptosis and calcium buffering are inversely related. In regions such as the cingulate and retrosplenial cortex, injury peaks at postnatal Day 7 (P7) and rapidly diminishes thereafter, whereas expression of calbindin (CB) and calretinin (CR) was relatively low from P0 to P7 and steadily increased from P7 to P14. At ages thereafter, CB and CR expression either remained stable then declined or rapidly declined. Parvalbumin (PV) was generally low-absent prior to P7 but expression dramatically increased from P10 onwards, peaking at P21. These studies suggest calcium entry (through N-methyl-D-aspartate receptor (NMDARs)) and buffering (by CaBPs) are integral to normal CNS maturation. Because schizophrenia is associated with glutamate hypo-function, developmental injury, and aberrant CaBP expression, our data indicate that this postnatal brain injury model may offer important insights into the nature of this disorder.