Posterior SMA Syndrome following subcortical stroke: contralateral akinesia reversed by visual feedback.

BACKGROUND: The supplementary motor area (SMA) plays a key role in motor programming and production and is involved in internally-cued movements. In neurological populations, SMA syndrome following a lesion to the "SMA proper" is characterized by transient impairment of voluntary movements and motor sequences. This syndrome is assumed to follow on from an interruption of the motor cortico-subcortical loop, and some case reports indicate that such a syndrome could occur after a brain lesion isolating the SMA from subcortical structures. AIM: To characterize the pattern of motor impairments in a patient whose stroke disconnects the SMA from the subcortical motor loop. METHOD: A patient developed a moderate transient left hemiparesis following a subcortical stroke in the right anterior cerebral artery area, which disconnected the SMA from basal ganglia. Eight days after the stroke, when the hemiparesis had regressed, the patient presented a specific SMA motor disorder of the left hand which manifested as an akinesia and was exacerbated when his visual attention was not directed towards his hand. We assessed finger tapping with left and right hands, eyes closed and open, in the left and right hemispace. We indexed movement speed as the number of taps filmed over 5-s periods. RESULTS: Left motor weakness (grasping strength of right hand: 49 kg and left hand: 41 kg) was resolved in a week. Ideomotor and ideational gestures and motor sequences were preserved. On the tapping task, left-hand tapping was slower than right-hand tapping. Critically, visual feedback improved tapping speed for the left, but not for the right, hand. The hemispace of the task execution had no effect on tapping performance. CONCLUSION: Our results suggest that SMA-basal ganglia disconnection decreases contralateral movement initiation and maintenance and this effect is partly compensated by visual cues.

Effects of oat ß-glucan on the macrophage cytokine response to herpes simplex virus 1 infection in vitro.

Oat ß-glucan can counteract the increased risk for Herpes Simplex Virus 1 (HSV-1) infection in mice, the effects of which have, at least in part, been attributed to macrophages. However, the specific responses of macrophages to oat ß-glucan treatment in this model have yet to be elucidated. We examined the effects of varying doses of oat ß-glucan on the pro-inflammatory cytokine response in both peritoneal and lung macrophages with and without exposure to HSV-1 infection in vitro. Peritoneal and lung macrophages were obtained from mice and cultured with varying concentrations of oat ß-glucan (0 (control), 10, 100, and 1,000 µg) for 24 h and supernatants were collected. A standardized dose of HSV-1 was added for a second 24 h incubation period after which supernatants were again collected. Samples were analyzed for interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) using enzyme linked immunosorbent assay (ELISA). In most cases, oat ß-glucan resulted in a dose-dependent increase in pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) in lung and peritoneal macrophages with and without exposure to HSV-1 infection. When comparing across macrophage source, this response was greater for IL-1ß and IL-6 in peritoneal macrophages and for TNF-α in lung macrophages. This may be a mechanism for the decreased risk for HSV-1 infection following oat ß-glucan feedings in mice.

When the brain remembers, but the patient doesn't: converging fMRI and EEG evidence for covert recognition in a case of prosopagnosia.

The role of the occipito-temporal cortex in visual awareness remains an open question and with respect to faces in particular, it is unclear to what extent the fusiform face area (FFA) may be involved in conscious identification. An answer may be gleaned from prosopagnosia, a disorder in which familiar faces are no longer recognized. This impairment has sometimes been reported to be associated with implicit processing of facial identity, although the neural substrates responsible for unconscious processing remain unknown. In this study, we addressed these issues by investigating the functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) responses to familiar and unfamiliar faces in a well-known prosopagnosic patient (P.S.). Our fMRI results show that faces known prior to the onset of prosopagnosia produce an increase in activation in the lateral fusiform gyrus encompassing the FFA, as well as the right middle frontal gyrus, when compared to unknown faces. This effect is not observed with photographs of celebrities dating after the onset of prosopagnosia. Furthermore, electrophysiological responses show that previously familiar faces differ from unfamiliar ones at around 550 msec. Since covert processing of familiarity is associated with activation in FFA, this structure does not appear to be sufficient to produce awareness of identity. Furthermore, the results support the view that FFA participates in face individuation.

Anti-inflammatory activity of select sorghum (Sorghum bicolor) brans.

The bran fractions of certain varieties of sorghum (Sorghum bicolor) grain are rich sources of phytochemicals and antioxidants. In this article, the anti-inflammatory actions of extracts of select sorghum brans were evaluated in two experimental inflammatory systems: (1) the release of cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells and (2) 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice. A 1:200 dilution of a 10% (wt/vol) ethanol extract of black sorghum bran significantly inhibited the secretion of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha. Ethanolic extracts of both black and sumac varieties of sorghum bran significantly reduced edema in inflamed ears as measured by ear thickness and ear punch weight 6 hours following TPA application. The degree of inhibition was similar to that observed with indomethacin. Black sorghum bran significantly diminished the increase in myeloperoxidase activity 24 hours following the application of TPA. No anti-inflammatory activity was observed with white and Mycogen sorghum bran varieties or with oat, wheat, or rice brans in the mouse ear model. The anti-inflammatory activity observed with these brans correlated with their phenolic content and antioxidant activity. These results demonstrate that select sorghum bran varieties possess significant anti-inflammatory activity.

Acquired prosopagnosia as a face-specific disorder: ruling out the general visual similarity account.

Prosopagnosia is classically defined as a disorder of visual recognition specific to faces, following brain damage. However, according to a long-standing alternative view, these patients would rather be generally impaired in recognizing objects belonging to visually homogenous categories, including faces. We tested this alternative hypothesis stringently with a well-documented brain-damaged prosopagnosic patient (PS) in three delayed forced-choice recognition experiments in which visual similarity between a target and its distractor was manipulated parametrically: novel 3D geometric shapes, morphed pictures of common objects, and morphed photographs of a highly homogenous familiar category (cars). In all experiments, PS showed normal performance and speed, and there was no evidence of a steeper increase of error rates and RTs with increasing levels of visual similarity, compared to controls. These data rule out an account of acquired prosopagnosia in terms of a more general impairment in recognizing objects from visually homogenous categories. An additional experiment with morphed faces confirmed that PS was specifically impaired at individual face recognition. However, in stark contrast to the alternative view of prosopagnosia, PS was relatively more impaired at the easiest levels of discrimination, i.e. when individual faces differ clearly in global shape rather than when faces were highly similar and had to be discriminated based on fine-grained details. Overall, these observations as well as a review of previous evidence, lead us to conclude that this alternative view of prosopagnosia does not hold. Rather, it seems that brain damage in adulthood may lead to selective recognition impairment for faces, perhaps the only category of visual stimuli for which holistic/configural perception is not only potentially at play, but is strictly necessary to individualize members of the category efficiently.

Role of brain macrophages on IL-1beta and fatigue following eccentric exercise-induced muscle damage.

Fatigue associated with recovery from muscle damage has recently been linked to increases in brain and muscle proinflammatory cytokines. However, little is known regarding the origin of these cytokines. Since macrophage-like cells in the brain are a primary source of cytokines, we used a brain specific macrophage depletion technique involving liposome encapsulated clodronate (CLD) to examine the role of macrophages on brain IL-1beta and fatigue following eccentric exercise-induced muscle damage. Mice were assigned to six groups: Downhill saline (DWNSAL), downhill clodronate (DWNCLD), uphill saline (UPSAL), uphill clodronate (UPCLD), non-running saline (CONSAL) or non-running clodronate (CONCLD). Mice were given intracerebroventricular (ICV) (10 microL) injections of clodronate-filled liposomes (CLD) to deplete macrophages, or saline-filled liposomes (SAL) and run on a treadmill at 22m/min and -14% (DWN) or 14% (UP) grade for 150 min. A subset of uphill and downhill running mice (n=40) was then run to fatigue on a treadmill at 36m/min, 8% grade at 24h after the uphill and downhill runs. A second subset of uphill, downhill, and control mice (n=30) was sacrificed 24h after the run for analysis of brain IL-1beta concentration. Histological examination confirmed previous reports that CLD administration reduced perivascular and meningeal macrophage subsets in the brain. CLD reduced IL-1beta concentration in the cortex of DWN mice (P<0.05), which was associated with enhanced treadmill performance 24h after both uphill and downhill runs (P<0.05) although the magnitude was greater following the downhill run. These results suggest that brain macrophages can contribute to the increase in brain IL-1beta and fatigue that are associated with recovery from exercise-induced muscle damage.

Top-down activation of fusiform cortex without seeing faces in prosopagnosia.

Face processing can be modified by bottom-up and top-down influences, but it is unknown how these processes interact in patients with face-recognition impairments (prosopagnosia). We investigated a prosopagnosic with lesions in right occipital and left fusiform cortex but whose right fusiform gyrus is intact and still activated during face-processing tasks. P.S., a patient with a well-established and selective agnosia for faces, was instructed to detect the presence of either faces or houses in pictures with different amounts of noise. The right fusiform face area (FFA) showed reduced responses to face information when visual images were degraded with noise. However, her right FFA still activated to noise-only images when she was instructed to detect faces. These results reveal that fusiform activation is still selectively modulated by task demands related to the anticipation of a face, despite severe face-recognition deficits and the fact that no reliable stimulus-driven response is evoked by actual facial information. Healthy controls showed stimulus-driven responses to faces in fusiform, and in right but not left occipital cortex, suggesting that the latter area alone might provide insufficient facial information in P.S. These results provide a novel account for residual activation of the FFA and underscore the importance of controlling task demands during functional magnetic resonance imaging.

Benefits of oat beta-glucan and sucrose feedings on infection and macrophage antiviral resistance following exercise stress.

Oat beta-glucan can counteract the exercise-induced increased risk for upper respiratory tract infection (URTI) in mice, which is at least partly mediated by its effects on lung macrophages. Substantial evidence in humans indicates that carbohydrate-containing sports drinks can offset the decreased immune function associated with stressful exercise. However, no studies in animals or humans have directly examined their effects on URTI using a controlled virus-challenge model. We examined the effects of sucrose feedings alone and in combination with oat beta-glucan on susceptibility to infection and on macrophage antiviral resistance in mice following stressful exercise. These effects were also examined in rested, nonimmunocompromised control mice. Mice were assigned to one of four groups: H(2)O (water), sucrose (S), oat beta-glucan (ObetaG), and sucrose + oat beta-glucan (S+ObetaG). ObetaG and S treatments consisted of a solution of 50% ObetaG and 6% sucrose, respectively, and were administered in drinking water for 10 consecutive days. Exercise consisted of a treadmill run to fatigue performed on three consecutive days. Mice were then intranasally inoculated with a standardized dose of herpes simplex virus 1 (HSV-1) and monitored for morbidity and mortality for 21 days. Additional mice were used to determine macrophage antiviral resistance. In the exercise experiment, S, ObetaG, and S+ObetaG all reduced morbidity (P < 0.05), while only S+ObetaG reduced mortality (P < 0.05). Macrophage antiviral resistance was also increased in S, ObetaG, and S+ObetaG treatments (P < 0.05). In resting controls, S and S+ObetaG reduced morbidity and mortality (P < 0.05) and showed a trend toward increased macrophage antiviral resistance. There was no significant additive effect of S and ObetaG in either control or exercised animals. These data extend our previous work on the benefits of oat beta-glucan to show that sucrose feedings have similar effects on susceptibility to respiratory infection and macrophage antiviral resistance in both resting controls and following exercise stress.

Emotional attention in acquired prosopagnosia.

The present study investigated whether emotionally expressive faces guide attention and modulate fMRI activity in fusiform gyrus in acquired prosopagnosia. Patient PS, a pure case of acquired prosopagnosia with intact right middle fusiform gyrus, performed two behavioral experiments and a functional imaging experiment to address these questions. In a visual search task involving face stimuli, PS was faster to select the target face when it was expressing fear or happiness as compared to when it was emotionally neutral. In a change detection task, PS detected significantly more changes when the changed face was fearful as compared to when it was neutral. Finally, an fMRI experiment showed enhanced activation to emotionally expressive faces and bodies in right fusiform gyrus. In addition, PS showed normal body-selective activation in right fusiform gyrus, partially overlapping the fusiform face area. Together these behavioral and neuroimaging results show that attention was preferentially allocated to emotional faces in patient PS, as observed in healthy subjects. We conclude that systems involved in the emotional guidance of attention by facial expression can function normally in acquired prosopagnosia, and can thus be dissociated from systems involved in face identification.

Executive disorders and perceived socio-emotional changes after traumatic brain injury.

Although socio-emotional changes are very frequently encountered after traumatic brain injury (TBI), the psychological mechanisms underlying these disorders are still poorly understood. This study aimed to explore the relationships between dysexecutive syndrome (assessed with the Behavioural Assessment of the Dysexecutive Syndrome [BADS]) and socio-emotional changes assessed by the Iowa scales of personality change (ISPC) in patients with TBI. The BADS was thus administered to 25 patients with TBI and to 25 healthy controls. Simultaneously, a close relative of each patient was given the ISPC in order to assess socio-emotional changes. Results indicated that patients displayed significantly lower executive performances than controls and experimented significant socio-emotional changes. The Modified Six Elements Test was the only subtask of the BADS to be significantly related to behavioural changes, and more specifically to externalizing disorders. It is concluded that executive functions, and especially multitasking, encompass processes whereby one can consciously control one's emotional reactions and behaviours.

Effect of IL-6 deficiency on susceptibility to HSV-1 respiratory infection and intrinsic macrophage antiviral resistance.

Cytokines play important roles in the mechanisms of disease development. Interleukin-6 (IL-6) is associated with clearance of herpes simplex virus (HSV) infections and in virus-induced immunopathology. However, the importance of IL-6 in host defense against HSV-1 respiratory infection is unknown. This study tested the effect of knockout mice deficient for IL-6 on susceptibility to HSV-1 respiratory infection and on intrinsic macrophage antiviral resistance to HSV-1. Control C57BL/6 IL-6+/+ mice and IL-6 knockout mice (IL-6-/-) were intranasally inoculated with 50 microL of a standardized dose (3.2 x 10(5)) of HSV-1. Morbidity, mortality, and symptom severity were monitored for 21 days. A subset of mice was sacrificed at 48-h postinfection and lungs were analyzed for viral titers. Peritoneal macrophages were obtained from a third set of mice and assayed for antiviral resistance to HSV-1. IL-6-/- increased morbidity by 84%, mortality by 84%, and symptom severity score on days 7.5 through 11 (p < 0.05). IL-6-/- increased virus titers in the lung 4-fold (p < 0.01) and resulted in a decrease in macrophage antiviral resistance (p < 0.001). Results indicate that IL-6 plays an important role in susceptibility to respiratory infection in mice, which may be mediated at least in part by its effect on macrophage antiviral resistance.

Galectin-3 gene inactivation reduces atherosclerotic lesions and adventitial inflammation in ApoE-deficient mice.

This study has examined the role of galectin-3 (GaL3), a multicompartmented N-acetyllactosamine-binding chimeric lectin, on atherogenesis in the ApoE-deficient mouse model of atherosclerosis. Pathological changes consisting of atheromatous plaques, atherosclerotic microaneurysms extending into periaortic vascular channels, and adventitial and periaortic inflammatory infiltrates were assessed in an equal number (n = 36) of apolipoprotein (Apo)E-deficient mice and ApoE-GaL3 double-knockout mice. These mice were divided into three age groups, 21 to 23 weeks, 25 to 31 weeks, and 36 to 44 weeks of age. Results of this morphological analysis have shown an age-related increase in the incidence of aorta atheromatous plaques and periaortic vascular channels in ApoE-deficient mice. By contrast ApoE/GaL3 double-knockout mice did not show an increase in pathological changes with age. The 36- to 44-week group of ApoE(-/-)/GaL3(-/-) mice had a significantly lower number of atherosclerotic lesions (P < 0.004) and fewer atheromatous plaques (P < 0.008) when compared with ApoE(-/-)/GaL3+/+ mice of the same age. ApoE(-/-)/GaL3(-/-) mice had a lower number of perivascular inflammatory infiltrates and mast cells than those found in ApoE(-/-)/GaL3+/+ mice. The reduced number of perivascular mast cells may have resulted in a low level of interleukin-4 that contributed to the reduction in the morphological parameters of atherogenesis correlated with the lack of GaL3 expression. The effect of GaL3 deficiency on atherogenesis decrease could be related to its function as a multifunctional protein implicated in macrophage chemotaxis, angiogenesis, lipid loading, and inflammation.

Quercetin reduces illness but not immune perturbations after intensive exercise.

PURPOSE: To investigate the effects of quercetin supplementation on incidence of upper respiratory tract infections (URTI) and exercise-induced changes in immune function. METHODS: Trained male cyclists (N=40) were randomized to quercetin (N=20) or placebo (N=20) groups and, under double-blind procedures, received 3 wk quercetin (1000 mg.d(-1)) or placebo before, during, and for 2 wk after a 3-d period in which subjects cycled for 3 h.d(-1) at approximately 57% Wmax. Blood and saliva samples were collected before and after each of the three exercise sessions and assayed for natural killer cell activity (NKCA), PHA-stimulated lymphocyte proliferation (PHA-LP), polymorphonuclear oxidative-burst activity (POBA), and salivary IgA output (sIgA). RESULTS: Pre- to postexercise changes in NKCA, PHA-LP, POBA, and sIgA did not differ significantly between quercetin and placebo groups. URTI incidence during the 2-wk postexercise period differed significantly between groups (quercetin=1/20 vs placebo=9/20, Kaplan-Meier analysis statistic=8.31, P=0.004). CONCLUSION: Quercetin versus placebo ingestion did not alter exercise-induced changes in several measures of immune function, but it significantly reduced URTI incidence in cyclists during the 2-wk period after intensified exercise.

Quercetin's influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA.

Trained male cyclists (n = 40) ingested quercetin (Q; n = 20) (1,000 mg/day) or placebo (P; n = 20) supplements under randomized, double-blinded methods for 3 wk before and during a 3-day period in which subjects cycled for 3 h/day at approximately 57% maximal work rate. Blood samples were collected before and after each exercise session and assayed for plasma IL-6, IL-10, IL-1ra, IL-8, TNF-alpha, and monocyte chemoattractant protein 1, and leukocyte IL-10, IL-8, and IL-1ra mRNA. Muscle biopsies were obtained before and after the first and third exercise sessions and assayed for NF-kappaB and cyclooxygenase-2 (COX-2), IL-6, IL-8, IL-1beta, and TNF-alpha mRNA. Postexercise increases in plasma cytokines did not differ between groups, but the pattern of change over the 3-day exercise period tended to be lower in Q vs. P for IL-8 and TNF-alpha (P = 0.094 for both). mRNA increased significantly postexercise for each cytokine measured in blood leukocyte and muscle samples. Leukocyte IL-8 and IL-10 mRNA were significantly reduced in Q vs. P (interaction effects, P = 0.019 and 0.012, respectively) with no other leukocyte or muscle mRNA group differences. Muscle NF-kappaB did not increase postexercise and did not differ between Q and P. Muscle COX-2 mRNA increased significantly postexercise but did not differ between Q and P. In summary, 1 g/day quercetin supplementation by trained cyclists over a 24-day period diminished postexercise expression of leukocyte IL-8 and IL-10 mRNA, indicating that elevated plasma quercetin levels exerted some effects within the blood compartment. Quercetin did not, however, influence any of the muscle measures, including NF-kappaB content, cytokine mRNA, or COX-2 mRNA expression across a 3-day intensified exercise period.

Oat beta-glucan effects on neutrophil respiratory burst activity following exercise.

UNLABELLED: Fatiguing exercise has been associated with a decrease in certain functions of neutrophils, whereas moderate exercise has generally been associated with an increase. Consumption of oat beta-glucan (ObetaG), a soluble fiber and mild immune system enhancer, may offset the immunosuppression associated with intense training and perhaps further enhance the benefits of moderate exercise. PURPOSE: To test the effects of ObetaG consumption on neutrophil function and number after both moderate and fatiguing exercise. METHODS: Male mice were assigned to one of six treatment groups. Fatiguing exercise mice (Ftg-ObetaG and Ftg-H2O) ran to volitional fatigue on a treadmill for three consecutive days, and moderate exercise mice (Mod-ObetaG and Mod-H2O) ran for six consecutive days for 1 h. Control mice (Con-ObetaG and Con-H2O) were exposed to the treadmill environment but did not run. ObetaG was consumed in the drinking water (approximately 0.6 mL x d(-1)) for 10 consecutive days. After rest or exercise on the last day of training, mice were given a 1-mL i.p. injection of thioglycollate. Mice were sacrificed 3 h later; neutrophils were harvested from the peritoneal cavity and counted, and their respiratory burst activity was measured using flow cytometry. RESULTS: Both moderate exercise and ObetaG increased neutrophil burst activity, whereas fatiguing exercise had no effect. Neutrophil number was increased by fatiguing exercise and ObetaG, but not moderate exercise. There were no additive effects of exercise and ObetaG on either of these variables. CONCLUSION: These data suggest that although not additive in their effects, both ObetaG and exercise can alter overall neutrophil respiratory burst activity (number and/or function), but only ObetaG increased both number and function, which may have important ramifications for defense against infection.

Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage.

Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness, and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investigated for its anti-inflammatory activity and may offset some of the damage and functional deficits associated with downhill running. This study examined the effects of curcumin on inflammation and recovery of running performance following downhill running in mice. Male mice were assigned to downhill placebo (Down-Plac), downhill curcumin (Down-Cur), uphill placebo (Up-Plac), or uphill curcumin (Up-Cur) groups and run on a treadmill at 22 m/min at -14% or +14% grade, for 150 min. At 48 h or 72 h after the up/downhill run, mice (experiment 1) underwent a treadmill performance run to fatigue. Another subset of mice was placed in voluntary activity wheel cages following the up/downhill run (experiment 2) and their voluntary activity (distance, time and peak speed) was recorded. Additional mice (experiment 3) were killed at 24 h and 48 h following the up/downhill run, and the soleus muscle was harvested for analysis of inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and plasma was collected for creatine kinase analysis. Downhill running decreased both treadmill run time to fatigue (48 h and 72 h) and voluntary activity (24 h) (P < 0.05), and curcumin feedings offset these effects on running performance. Downhill running was also associated with an increase in inflammatory cytokines (24 h and 48 h) and creatine kinase (24 h) (P < 0.05) that were blunted by curcumin feedings. These results support the hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage.

Clinical assessment of motor function: a processes oriented instrument based on a speed-accuracy trade-off paradigm.

In this study, we developed a digitizing tablet-based instrument for the clinical assessment of human voluntary movements targeting motor processes of planning, programming and execution. The tool was used to investigate an adaptation of Fitts' reciprocal tapping task [10], comprising four conditions, each of them modulated by three indices of difficulty related to the amplitude of movement required. Temporal, spatial and sequential constraints underlying the various conditions allowed the intricate motor processes to be dissociated. Data obtained from a group of elderly healthy subjects (N=50) were in agreement with the literature on motor control, in the temporal and spatial domains. Speed constraints generated gains in the temporal domain and costs in the spatial one, while spatial constraints generated gain in the spatial domain and costs in the temporal one; finally, sequential constraints revealed the integrative nature of the cognitive operations involved in motor production. This versatile instrument proved capable of providing quantitative, accurate and sensitive measures of the various processes sustaining voluntary movement in healthy subjects. Altogether, analyses performed in this study generated a theoretical framework and reference data which could be used in the future for the clinical assessment of patients with various movement disorders, in particular Parkinson's disease.

Quercetin ingestion does not alter cytokine changes in athletes competing in the Western States Endurance Run.

The purpose of this study was to measure the influence of quercetin on plasma cytokines, leukocyte cytokine mRNA, and related variables in ultramarathoners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin and placebo groups and under double-blinded methods ingested 1000 mg/day quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood samples the morning before the race and 15-30 min postrace. Significant prerace to postrace WSER increases were measured for nine proinflammatory and anti-inflammatory plasma cytokines, cortisol (quercetin = 94%, placebo = 96%), serum C-reactive protein (CRP) (mean +/- SE absolute increase, quercetin = 31.8 +/- 4.2, placebo = 38.2 +/- 5.0 mg/L), and creatine kinase (CK) (quercetin = 21,575 +/- 3,977, placebo = 19,455 +/- 3,969 U/L), with no significant group differences. Interleukin-6 (IL-6) mRNA did not change post-WSER, with a significant decrease measured for leukocyte IL-8 mRNA (0.21 +/- 0.03-fold and 0.25 +/- 0.04-fold change from rest, quercetin and placebo, respectively) and significant increases for IL-1Ra mRNA (1.43 +/- 0.18-fold and 1.40 +/- 0.16-fold change, quercetin and placebo, respectively) and IL-10 mRNA (12.9 +/- 3.9-fold and 17.2 +/- 6.1-fold change, quercetin and placebo, respectively), with no significant differences between groups. In conclusion, quercetin ingestion (1 g/day) by ultramarathon athletes for 3 weeks before a competitive 160-km race significantly increased plasma quercetin levels but failed to attenuate muscle damage, inflammation, increases in plasma cytokine and hormone levels, and alterations in leukocyte cytokine mRNA expression.

Influence of carbohydrate on immune function following 2 h cycling.

The influence of carbohydrate compared with placebo ingestion on changes in immune cell counts and functions following 2 h intensive cycling was studied in 12 trained cyclists who functioned as their own controls. The subjects performed two tests 2 weeks apart where they cycled for 2 h at approximately 64% Watts(max) while receiving 4 mL x kg(-1) x 15 min(-1) carbohydrate (6%) (Cho) or placebo (Pla) beverages. Blood samples were collected 30 min preexercise, and immediately and 1 h postexercise. The samples were assayed for plasma cortisol and epinephrine, blood leukocyte subset counts, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Compared with Pla ingestion, Cho attenuated exercise-induced changes in plasma cortisol, blood neutrophil, and monocyte counts, but not in total blood lymphocyte, T cell, and NK cell counts, PHA-induced lymphocyte proliferation, and NKCA. Thus despite a strong attenuating influence of carbohydrate ingestion on exercise-induced changes in plasma cortisol and blood neutrophil and monocyte counts, other immune measures related to lymphocyte subset counts, and function were unaffected.

Role of brain IL-1beta on fatigue after exercise-induced muscle damage.

Brain cytokines, induced by various inflammatory challenges, have been linked to sickness behaviors, including fatigue. However, the relationship between brain cytokines and fatigue after exercise is not well understood. Delayed recovery of running performance after muscle-damaging downhill running is associated with increased brain IL-1beta concentration compared with uphill running. However, there has been no systematic evaluation of the direct effect of brain IL-1beta on running performance after exercise-induced muscle damage. This study examined the specific role of brain IL-1beta on running performance (either treadmill or wheel running) after uphill and downhill running by manipulating brain IL-1beta activity via intracerebroventricular injection of either IL-1 receptor antagonist (ra; downhill runners) or IL-1beta (uphill runners). Male C57BL/6 mice were assigned to the following groups: uphill-saline, uphill-IL-1beta, downhill-saline, or downhill-IL-1ra. Mice initially ran on a motor-driven treadmill at 22 m/min and -14% or +14% grade for 150 min. After the run, at 8 h (wheel cage) or 22 h (treadmill), uphill mice received intracerebroventricular injections of IL-1beta (900 pg in 2 microl saline) or saline (2 microl), whereas downhill runners received IL-1ra (1.8 microg in 2 microl saline) or saline (2 microl). Later (2 h), running performance was measured (wheel running activity and treadmill run to fatigue). Injection of IL-1beta significantly decreased wheel running activity in uphill runners (P<0.01), whereas IL-1ra improved wheel running in downhill runners (P<0.05). Similarly, IL-1beta decreased and Il-1ra increased run time to fatigue in the uphill and downhill runners, respectively (P<0.01). These results support the hypothesis that increased brain IL-1beta plays an important role in fatigue after muscle-damaging exercise.