The prominent role of perceptual salience in object discrimination: overt discrimination of graspable side does not activate grasping affordances.

Responses to object stimuli are often faster when jutting handles are aligned with responding hands, than when they are not: handle-to-hand correspondence effects. According to a location coding account, locations of visually salient jutting parts determine the spatial coding of objects. This asymmetry then facilitates same-sided responses compared to responses on the opposite side. Alternatively, this effect has been attributed to grasping actions of the left or the right hand afforded by the handle orientation and independent of its salience (affordance activation account). Our experiments were designed to disentangle the effects of pure salience from those of affordance activations. We selected pictures of tools with one salient and non-graspable side, and one graspable and non-salient side (non-jutting handle). Two experiments were run. Each experiment had two groups of participants: one group discriminated the location of the salient side of the object stimuli; the other group discriminated the location of the graspable side of them. In Experiment 1, responses were left and right button presses; in Experiment 2, they were left and right button presses plus reach-and-grasp actions. When visual salience was removed from graspable sides, no correspondence effect was observed between their orientation and the responding hands in both the experiments. Conversely, when salience depended on non-graspable portions, a correspondence effect was produced between their orientation and the responding hand. Overt attention to graspable sides did not potentiate any grasping affordance even when participants executed grasping responses in addition to button presses. Results support the location coding account: performance was influenced by the spatial coding of visually salient properties of objects.

Towards a unified model of event-related potentials as phases of stimulus-to-response processing.

This study demonstrates the utility of combining principles of connectionist theory with a sophisticated statistical approach, structural equation modeling (SEM), to better understand brain-behavior relationships in studies using event-related potentials (ERPs). The models show how sequential phases of neural processing measured by averaged ERP waveform components can successfully predict task behavior (response time; RT) while accounting for individual differences in maturation and sex. The models assume that all ERP measures are affected by individual differences in physical and mental state that inflate measurement error. ERP data were collected from 154 neurotypical children (7-13 years, M = 10.22, SD = 1.48; 74 males) performing a cued Go/No-Go task during two separate sessions. Using SEM, we show a latent variable path model with good fit (e.g., χ2(51) = 56.20, p = .25; RMSEA = .03; CFI = .99; SRMR = .06) yielding moderate-to-large predictive coefficients from N1 through the E-wave latent variables (N1 ß = -.29 → P2 ß = -.44 → N2 ß = .28 → P3 ß =.64→ E-wave), which in turn significantly predicted RT (ß =.34, p = .02). Age significantly related to N1 and P3 latent variables as well as RT (ß =.31, -.58, & -.40 respectively), and Sex significantly related to the E-wave latent variable and RT (ß =.36 & 0.21 respectively). Additionally, the final model suggested that individual differences in emotional and physical state accounted for a significant proportion of variance in ERP measurements, and that individual states systematically varied across sessions (i.e., the variance was not just random noise). These findings suggest that modeling ERPs as a system of inter-related processes may be a more informative approach to examining brain-behavior relationships in neurotypical and clinical groups than traditional analysis techniques.

Learning to be in control involves response-specific mechanisms.

Conflict adaptation refers to our ability to modulate our attention in line with changing situational demands, so we can engage in goal-directed behavior. While there is ample evidence demonstrating that such adaptation in conflict tasks can be captured using different response modalities, it remains unknown whether these effects rely on domain-general mechanisms applied to different response modalities, or are the result of more inherently response-specific processes. Here, we used an individual-differences approach to evaluate whether conflict adaptation in two highly similar tasks using different response modalities are related. Specifically, participants performed two versions of a Stroop task, one in which they responded via key presses and one in which they responded via mouse movements. In both tasks, we manipulated the item-specific proportion of (in)congruent trials (80% vs. 20% congruent). This allowed us to evaluate the item-specific proportion congruency (ISPC) effect, a hallmark indicator of conflict adaptation. ISPC effects were observed in both response modalities. However, we found no indications that individual differences in the ISPC effects of the two response modalities were related. This raises the question whether findings from studies on conflict adaptation measured by different modalities can reliably be compared. Furthermore, these results suggest that response modality plays a more integrative role in these adaptive processes, rather than being the mere output of a domain-general control mechanism. This is consistent with contingency learning accounts of the ISPC effect and associative learning models of cognitive control.

Comparación de la respuesta inicial luego de la ablación con 30 mCi de 131I versus no ablación en pacientes con cáncer diferenciado de tiroides de bajo riesgo de recurrencia. Estudio prospectivo multicéntrico / Comparison of initial response to treatment after remnant ablation (RA) with 30 mCi of 131 I versus no RA in patients with differentiated thyroid cancer with low risk of recurrence. Multicentric prospective study

RESUMEN Material y métodos Estudio prospectivo multicéntrico. Se incluyeron 174 pacientes con CDT tratados consecutivamente desde junio 2014 hasta mayo 2015. Se los dividió en 2 grupos (ablacionados y no ablacionados) con 87 pacientes incluidos en cada uno. La respuesta inicial al tratamiento se determinó con la medición de tiroglobulina, anticuerpos anti-tiroglobulina y ecografía de cuello. Resultados Se compararon las características basales de ambos grupos y no se evidenciaron diferencias estadísticamente significativas: sexo femenino 84% y 88% (p = 0,5); edad promedio de 46,8 y 47,5 años (p = 0,7); carcinoma papilar variedad clásico 68% y 75,9% (p = 0,15), respectivamente. El resto de las características basales como tamaño tumoral, bilateralidad, multifocalidad, tiroiditis de Hashimoto y estadio tumoral tampoco mostraron diferencias significativas. La evaluación de la respuesta inicial al tratamiento se realizó en 64 pacientes del grupo ablacionado y en 76 del grupo no ablacionado. Se observó una respuesta excelente en 81% de pacientes ablacionados vs. 87% del grupo no ablacionado, con una frecuencia de respuesta estructural incompleta de 1,6% y 1,4%, respectivamente, (p = 0,9). Un 17% de los ablacionados y 12% de los no ablacionados presentaron una respuesta indeterminada. Conclusión: Los pacientes de bajo riesgo, ablacionados o no, presentan similares frecuencias de respuesta inicial excelente y estructural incompleta. El seguimiento a largo plazo podrá definir si estas respuestas iniciales se mantienen en el tiempo, lo que permitirá reducir la indicación de ablación con radioyodo en este grupo de pacientes con CDT.

ABSTRACT Patients and methods We included 174 patients; 87 patients in each group (ablated and nonablated). Assessment of the initial response to treatment was performed by measurement of thyroglobulin and anti-thyroglobulin antibodies and by neck ultrasonography. Results Baseline characteristics of both groups were compared, and no statistically significant differences were found: female sex 84% and 88,5%, respectively, (p = 0.5); mean age of 46.8 and 47.5 years, respectively (p = 0.7); papillary carcinoma classic variant 68% and 75.9%, respectively (p = 0.15). The remaining of the baseline characteristics such as tumor size, presence of bilaterality, multifocality, Hashimoto's thyroiditis and tumor stage were not statistically significant, either. The evaluation of the response to treatment was finally performed in 64 patients from the ablated group and in 76 from the non-ablated group. An excellent response to treatment was observed in 81% of ablated patients vs. 87% of the non-ablated group, with a frequency of structural incomplete response of 1.6% and 1.4%, respectively (p = 0.9). On the other hand, 17% and 12% of patients in each group had an indeterminate response. Conclusion Low-risk ablated and non-ablated patients have a similar frequency of excellent initial and structural incomplete response to treatment. Long-term follow-up is needed to establish whether these initial responses are maintained over time, and thus further refine the indications of RA in this group of patients with DTC.

Distinct phase-amplitude couplings distinguish cognitive processes in human attention.

Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process.

Participation of TLR2 and TLR4 in Cytokines Production by Patients with Symptomatic and Asymptomatic Chronic Chagas Disease.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30-40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury. This control was found to be responsible for no clinical manifestations in asymptomatic individuals. Toll-like receptors (TLRs) are extremely important in defining the cytokine profile released in response to a micro-organism. We found that patients with the cardiac form predominantly released the pro-inflammatory cytokines: IFN-γ, TNF-α and IL-17 with the involvement of both, TLR2 and TLR4. In contrast, patients with asymptomatic disease release predominantly the anti-inflammatory cytokines IL-10 and TGF-ß, but also with TLR2 and TLR4 participation. The mechanisms by which stimulation of the same TLRs results in release of different pattern of cytokines, depending on the patients group that is being evaluated, are discussed.

HLA-DR3-DQ2 mice do not develop ataxia in the presence of high titre anti-gliadin antibodies.

Recently, it has been suggested that anti-gliadin antibodies (αGAb) may produce "gluten ataxia", even in the absence of celiac disease enteropathy. αGAb are reportedly present in 12-50 % of patients with sporadic ataxia, but also in 12 % of the general population, such that the importance of αGAb as a cause of sporadic ataxia is not conclusively settled. We aimed to determine whether mice transgenic for HLA-DR3-DQ2 and immunised with gliadin to achieve high titres of αGAb would develop ataxia and/or cerebellar damage. From 6 weeks of age, HLA-DR3-DQ2 transgenic mice were immunised fortnightly with gliadin (n = 10) or a saline control (n = 6) in adjuvant. Serum titres were measured by αGAb enzyme-linked immunosorbent assay. At 24 weeks of age, mice were tested for locomotor function using the accelerating rotarod, ledged beam, ink-paw gait, and several neurological severity score subtests. Brains were then collected and processed for immunohistochemistry. Sections were analysed for lymphocytic infiltration, changes in morphology and Purkinje cell (PC) dendritic volume and the number of PCs counted via unbiased stereology. Gliadin-immunised mice developed high αGAb titres while controls did not. There was no statistically significant difference between the gliadin and sham-immunised HLA-DR3-DQ2 mice on any of the tests of motor coordination, in lymphocytic infiltration, PC number or in dendritic volume. High levels of αGAb are not sufficient to produce ataxia or cerebellar damage in HLA-DR3-DQ2 transgenic mice.

Chronic stress-induced changes in pro-inflammatory cytokines and spinal glia markers in the rat: a time course study.

BACKGROUND/AIMS: Spinal glia activation has been proposed as one mechanism underlying visceral hyperalgesia in a rodent model of chronic stress. In order to assess the possible role of changes in circulating cytokines and in blood-spinal cord barrier (BSCB) permeability in spinal glia activation, we studied the time course of peripheral and spinal pro-inflammatory cytokines and of spinal and satellite glia markers in response to repeated water avoidance (WA) stress. METHODS: Spinal cords and dorsal root ganglion cells (DRGs) were collected from control rats, rats exposed to 1-hour WA, or 1-hour WA daily for 5 days or 1-hour WA daily for 10 days. RESULTS: We demonstrated a time-dependent change in circulating IL-1ß and spinal IL-1ß, IL-6 and TNF-α in stressed animals compared with controls. We found altered expression of the astrocyte markers GFAP and Connexin 43 in spinal and DRG samples at different time points. Finally, WA was associated with increased BSCB permeability. CONCLUSIONS: These findings confirm the concept that both peripheral and spinal immune markers are altered after chronic WA and suggest a possible link between stress-induced increase of peripheral pro-inflammatory cytokines, changes in satellite glial cells, increase in BSCB permeability and increase in spinal pro-inflammatory mediators suggesting glia activation.

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 ß and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Prolonged increase in rat hippocampal chemokine signalling after status epilepticus.

Temporal lobe epilepsy (TLE) is one of the most common focal epilepsy syndromes. In a genome-wide expression study of the human TLE hippocampus we previously showed up-regulation of genes involved in chemokine signalling. Here we investigate in the rat pilocarpine model for TLE, whether changes in chemokine signalling occur during epileptogenesis and are persistent. Therefore we analysed hippocampal protein expression and cellular localisation of CCL2, CCL4, CCR1 and CCR5 after status epilepticus. We found increased CCL4 (but not CCL2) expression in specific populations of hilar astrocytes at 2 and 19 weeks after SE concomitant with a persistent up-regulation of its receptor CCR5. Our results show an early and persistent up-regulation of CCL4/CCR5 signalling during epileptogenesis and suggest that CCL4 signalling, rather than CCL2 signalling, could have a role in the epileptogenic process.

Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells.

The functional roles of memory B and T lymphocytes underlie the phenomenal success of prophylactic vaccinations, which have decreased morbidities and mortalities from infectious diseases globally over the last 50 years. However, it is becoming increasingly appreciated that memory cells are also capable of mediating the pathology associated with autoimmune disorders and transplant rejection, and may pose a significant barrier to future clinical advancement in immunoregulation. Therefore, understanding the unique properties of memory lymphocytes (as compared to their naive precursors) is a major area of investigation. Here, we focus on one of those singular properties of memory T cells (T(M))-rapid recall. As will be discussed in more detail, rapid recall refers to the ability of quiescent T(M) cells to efficiently and robustly express 'effector functions' following stimulation. Studies that have advanced our understanding of T(M) cells' rapid recall using CD4(+) T cells have been expertly reviewed elsewhere, so we will focus primarily on studies of CD8(+) T cells. We will first review the different ways that CD8(+) T(M) cells can be generated, followed by discussing how this influences their functional properties in the settings of immune protection and pathology. Then, rapid recall ability will be discussed, with emphasis placed on what is currently known about the mechanisms that underlie this unique property of T(M) cells.

Stiff person syndrome: presentation of a case with repetitive complex discharges in electromiograms.

INTRODUCTION: Stiff person syndrome is characterized by rigidity of axial and proximal limb muscles, associated with muscle spasms, triggered by unexpected acoustic or somesthetic stimuli. It usually has an autoimmune basis, in which the blood contains antiglutamate decarboxylase antibodies, and is associated with different types of autoimmune diseases. The electromyogram provides evidences of continuous muscular activity. CASE REPORT: A 41-year-old woman with a history of diabetes mellitus type I, Hashimoto thyroiditis, vitiligo, and pernicious anemia developed symptoms compatible with stiff person syndrome. In the electromyogram, in addition to continuous muscular activity, there was evidence of complex repetitive activity in the form of doublets and triplets. CONCLUSIONS: Given the absence of clinical or electrophysiological neuropathic affectation, the presence of doublets and triplets in our patient could be due to a subclinical functional alteration of alpha motoneurons. They could produce the complex repetitive discharges when released from the inhibition mediated by GABAergic neurons.

Hepatic nuclear factor kappa B regulates neutrophil recruitment to the injured brain.

Acute brain injury is associated with induction of hepatic chemokine expression, which is an essential element in the subsequent recruitment of leukocytes to the damaged brain. To further understand the significance of the hepatic inflammatory response, we focused on nuclear factor (NF)-kappa B, a pivotal regulator of inflammation. Nondestructive real-time whole-body imaging was undertaken in the 3XNF-kappa B-luciferase mouse to monitor NF-kappa B activation. Acute brain injury induced by intracerebral injection of interleukin-1 provoked rapid activation of hepatic and CNS NF-kappa B, with only minimal changes in other organs. Elevated NF-kappa B in the brain was limited to the site of the lesion, whereas hepatic NF-kappa B was widespread. The function of NF-kappa B in this model was determined by monitoring leukocyte recruitment to the liver and brain of nf kappa b1 mice, which lack the anti-inflammatory p50:p50 NF-kappa B homodimer. Brain injury in the nf kappa b1 mice was associated with increased neutrophil recruitment to the liver and brain compared with wild-type mice, thereby confirming a regulatory role for the NF-kappa B system. To determine the role of hepatic NF-kappa B, it was selectively inhibited by intravenous adenoviral-mediated delivery of an I kappa B alpha super-repressor. This treatment significantly reduced the numbers of neutrophils recruited to the brain. In conclusion, acute brain injury is associated with rapid and robust activation of hepatic NF-kappa B, which is required for efficient mobilization of circulating leukocytes to the brain.

IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats.

Although it has been shown that pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) facilitate perception of noxious inputs at the spinal level, the mechanisms have not been understood. This study determined the cell type that produces IL-1beta, the co-localization of IL-1 receptor type I (IL-1RI) and Fos and NR1 in the spinal cord, and the effects of IL-1 receptor antagonist (IL-1ra) on NR1 phosphorylation and hyperalgesia in a rat model of inflammatory pain. Phosphorylation of NR1, an essential subunit of the NMDA receptor (NMDAR), is known to modulate NMDAR activity and facilitate pain. Hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08ml, 40microg Mycobacterium tuberculosis) into one hind paw of each rat. Paw withdrawal latency (PWL) was tested before CFA (-48h) for baseline and 2 and 24h after CFA to assess hyperalgesia. IL-1ra was given (i.t.) 24h before CFA to block the action of basal IL-1beta and 2h prior to each of two PWL tests to block CFA-induced IL-1beta. Spinal cords were removed for double immunostaining of IL-1beta/neuronal marker and IL-1beta/glial cell markers, IL-1RI/Fos and IL-1RI/NR1, and for Western blot to measure NR1 phosphorylation. The data showed that: (1) astrocytes produce IL-1beta, (2) IL-1RI is localized in Fos- and NR1-immunoreactive neurons within the spinal dorsal horn, and (3) IL-1ra at 0.01mg/rat significantly increased PWL (P<0.05) and inhibited NR1 phosphorylation compared to saline control. The results suggest that spinal IL-1beta is produced by astrocytes and enhances NR1 phosphorylation to facilitate inflammatory pain.

Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring.

Growing evidence suggests that maternal health during the prenatal period is a critical determinant of adult immuno-competence. This study aimed to characterise the innate immune response to bacterial exposure in rat offspring following maternal exposure to a pro-inflammatory stimulus. The offspring's innate immune responses were investigated at four developmental timepoints in the rat by determination of immune cell subtypes and TNF-alpha and IL-1beta response to in-vivo LPS exposure. The pre-weaned offspring of exposed dams demonstrated no immune response to the LPS challenge, whereas control offspring responded with a typical elevation in cytokine levels. In pubescence no differences were observed between the responses of the control and exposed offspring. In adulthood and senescence, offspring of endotoxin treated dams had significantly less monocytes in circulation than control offspring and differential sex effects were only evident in these older animals. The developmental profile of immune functioning following prenatal immune activation has not previously been demonstrated. This study highlights the prenatal period as one of importance in determining later immune function.

Lipopolysaccharide induces a spinal learning deficit that is blocked by IL-1 receptor antagonism.

Previous studies have shown that spinal neurons are capable of supporting a form of instrumental conditioning. Subjects receiving a spinal transection will learn to maintain a flexion response after exposure to shock contingent on leg position. In contrast, subjects receiving shock irrespective of leg position will not show increased flexion duration. Activation of the immune system has deleterious effects on learning in intact animals, but the impact of immune system activation on learning spinal animals is not known. We found that a large dose of i.p. LPS (1.0mg/kg) significantly disrupted the acquisition of the instrumental flexion response. The LPS-induced learning deficit was not prevented by preexposure to contingent shock (i.e. immunization) (Experiment 2). Co-administration of the iNOS inhibitor L-NIL (0.1, 1.0 and 10.0 microg/microL) failed to block the deficit (Experiment 3). Co-administration of an IL-1 receptor antagonist (r-metHuIL-1ra [10.0, 30.0 and 100.0 microg/microL) prevented the LPS-induced learning deficit when given in a dose of 100.0 microg/microL(i.t.) only (Experiment 4). Findings indicate a role for spinal IL-1 in the decreased plasticity following LPS administration.

HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain.

BACKGROUND: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo. RESULTS: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1beta, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain. CONCLUSION: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.

Maternal aggression persists following lipopolysaccharide-induced activation of the immune system.

Lactating females direct aggressive behaviors towards intruders presumably to reduce the likelihood of infanticide of their pups. Infected animals display a constellation of responses that include lethargy, anorexia, and decreased social interactions. This suite of responses is referred to as sickness behavior, and is putatively part of an adaptive strategy to aid the organism in recovery from infection. Previous work has suggested that animals can suppress the behavioral symptoms of sickness in order to engage in adaptive behaviors. To test whether adaptive nest defense is affected by illness, dams received a peripheral injection of either saline or lipopolysaccharide (LPS [50, 400, or 1000 microg/kg]), a non-replicating component of bacterial cell walls that activates the immune system. Simulated infection with LPS reduced body mass and food intake in dams and interfered with litter growth in a dose-dependent manner. Generally, nest defense was unaffected by LPS; the proportion of dams displaying maternal aggression against a male intruder, as well as the latency and duration of aggressive encounters were only suppressed at the highest LPS dose tested. Further, LPS treatment also altered non-agonistic behavior during the aggression test as indicated by reduced social investigation of the intruder and an increased time spent immobile during the session. LPS administration also significantly increased serum corticosterone concentrations in lactating females. These findings suggest that maternal aggression is not suppressed by LPS-evoked immune activation at doses that attenuate other aspects of maternal and social behavior.

Comparison of early and late responses to antigen of sensitized guinea pig parenchymal lung strips.

The peripheral lung parenchyma has been studied as a component of the asthmatic inflammatory response. During induced constriction, tissue resistance increases in different asthma models. Approximately 60% of the asthmatic patients show early and late responses. The late response is characterized by more severe airway obstruction. In the present study, we evaluated lung parenchymal strips mechanics in ovalbumin-sensitized guinea pigs, trying to reproduce both early and late inflammatory responses. Oscillatory mechanics of lung strips were performed in a control group (C), in an early response group (ER), and in two late response groups: 17 h (L1) and 72 h (L2) after the last ovalbumin challenge. Measurements of resistance and elastance were obtained before and after ovalbumin challenge in C and ER groups and before and after acetylcholine challenge in all groups. Using morphometry, we assessed the density of eosinophils and smooth muscle cells, as well as collagen and elastin content in lung strips. The baseline and postagonist values of resistance and elastance were increased in ER, L1, and L2 groups compared with C (P < or = 0.001). The morphometric analysis showed an increase in alveolar eosinophil density in ER and L2 groups compared with C (P < 0.05). There was a significant correlation between eosinophil density in parenchymal strips of C, L1, and L2 groups and values of resistance and elastance postacetylcholine (r = 0.71, P = 0.001 and r = 0.74, P < 0.001, respectively). The results show that the lung parenchyma is involved in the late response, and the constriction response in this phase is related to the eosinophilic inflammation.

Peripheral injection of lipopolysaccharide prevents brain recruitment of leukocytes induced by central injection of interleukin-1.

I.c.v. injection of interleukin-1beta induces infiltration of leukocytes into the brain. I.p. injection of bacterial endotoxin lipopolysaccharide induces the expression of interleukin-1 in the CNS without causing the entry of leukocytes into the brain. This suggests that during systemic inflammation trafficking of potentially damaging leukocytes into the CNS is inhibited. In this study, we investigated the effects of peripheral injection of lipopolysaccharide on brain leukocyte recruitment induced by i.c.v.-interleukin-1 in mice. I.c.v.-interleukin-1 induced widespread infiltration of leukocytes into the brain 16 h after the injection. Pretreatment with i.p.-lipopolysaccharide 2 h before the i.c.v. interleukin-1 injection completely blocked interleukin-1-induced leukocyte infiltration, whereas i.p.-LPS only attenuated the effect of interleukin-1 if it was given 12 h before i.c.v. interleukin-1 injection. I.p.-lipopolysaccharide given 24 h before i.c.v. interleukin-1 injection did not alter interleukin-1 induced leukocyte infiltration. I.c.v.-interleukin-1 induced expression of p- and e-selectins in brain vasculatures prior to the appearance of leukocytes in the brain parenchyma. Induction of p- and e-selectin was inhibited by the pretreatment of i.p.-lipopolysaccharide 2 h, but not 24 h, before i.c.v.-interleukin-1 injection. I.c.v.-interleukin-1-induced leukocyte infiltration was diminished in both e- and p- selectin knockout animals. These results suggest that systemic inflammation actively inhibits recruitment of leukocytes by CNS. Inhibition of the expression of p- and e-selectins is a mechanism by which peripheral inflammation regulate CNS leukocyte recruitment.