Exposure to repetitive head impacts is associated with corpus callosum microstructure and plasma total tau in former professional American football players

BACKGROUND: Exposure to repetitive head impacts (RHI) is associated with an increased risk of later-life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. PURPOSE: To investigate whether RHI exposure is associated with later-life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. STUDY TYPE: Retrospective cohort study. POPULATION: Seventy-five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. FIELD STRENGTH/SEQUENCE: Diffusion-weighted echo-planar MRI at 3 T. ASSESSMENT: Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self-report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free-water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1-7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT-A) and Part B (TMT-B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF-A). STATISTICAL TESTS: Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. RESULTS: RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT-A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT-B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT-A (FA, r = 0.36; AD, r = 0.28), TMT-B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29). DATA CONCLUSION: These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1

Fine root dynamics across pantropical rainforest ecosystems

Fine roots constitute a significant component of the net primary productivity (NPP) of forest ecosystems but are much less studied than above-ground NPP. Comparisons across sites and regions are also hampered by inconsistent methodologies, especially in tropical areas. Here, we present a novel dataset of fine root biomass, productivity, residence time, and allocation in tropical old-growth rainforest sites worldwide, measured using consistent methods, and examine how these variables are related to consistently determined soil and climatic characteristics. Our pantropical dataset spans intensive monitoring plots in lowland (wet, semi-deciduous, deciduous) and montane tropical forests in South America, Africa, and Southeast Asia (n=47). Large spatial variation in fine root dynamics was observed across montane and lowland forest types. In lowland forests, we found a strong positive linear relationship between fine root productivity and sand content, this relationship was even stronger when we considered the fractional allocation of total NPP to fine roots, demonstrating that understanding allocation adds explanatory power to understanding fine root productivity and total NPP. Fine root residence time was a function of multiple factors: soil sand content, soil pH, and maximum water deficit, with longest residence times in acidic, sandy, and water-stressed soils. In tropical montane forests, on the other hand, a different set of relationships prevailed, highlighting the very different nature of montane and lowland forest biomes. Root productivity was a strong positive linear function of mean annual temperature, root residence time was a strong positive function of soil nitrogen content in montane forests, and lastly decreasing soil P content increased allocation of productivity to fine roots. In contrast to the lowlands, environmental conditions were a better predictor for fine root productivity than for fractional allocation of total NPP to fine roots, suggesting that root productivity is a particularly strong driver of NPP allocation in tropical mountain regions.Output Status: Forthcoming/Available Online Additional co-authors: Christopher E. Doughty, Imma Oliveras, Darcy F. Galiano Cabrera, Liliana Durand Baca, Filio Farfán Amézquita, Javier E. Silva Espejo, Antonio C.L. da Costa, Erick Oblitas Mendoza, Carlos Alberto Quesada, Fidele Evouna Ondo, Josué Edzang Ndong, Vianet Mihindou, Natacha N’ssi Bengone, Forzia Ibrahim, Shalom D. Addo-Danso, Akwasi Duah-Gyamfi, Gloria Djaney Djagbletey, Kennedy Owusu-Afriyie, Lucy Amissah, Armel T. Mbou, Toby R. Marthews, Daniel B. Metcalfe, Luiz E.O. Aragão, Ben H. Marimon-Junior, Beatriz S. Marimon, Noreen Majalap, Stephen Adu-Bredu, Miles Silman, Robert M. Ewers, Patrick Meir, Yadvinder Malh

Deterioration of metabolic coronary regulation in hemorrhagic shock. Role of hypoxia and the renin-angiotensin system.

The effect of hypoxia and the renin-angiotensin system on metabolic coronary regulation in hemorrhagic shock was studied in 22 anesthetized open-chest dogs. Left circumflex coronary blood flow was measured with an electromagnetic flowmeter. Dogs were ventilated with room air (n = 8) or 100% oxygen (n = 7). A third group of dogs was ventilated with room air and bilaterally nephrectomized 5 h prior to starting the experimental protocol (n = 7). After control data had been obtained, dogs were bled from the femoral arteries into a pressurized reservoir which maintained blood pressure at 45 +/- 1 mmHg. The angiotensin II receptor blocker, saralasin, was then infused i.v. (0.1, 1.0, 10.0 micrograms/kg per min). Coronary blood flow was reduced by hemorrhage, and no significant difference existed in coronary flow during hemorrhage among the three groups. Coronary sinus oxygen saturation was diminished in control animals during hemorrhage from 26% +/- 1% to 17% +/- 1% (P less than 0.05) but normal in 100% oxygen ventilated animals (30% +/- 3%) and in nephrectomized dogs (34% +/- 4%). Coronary oxygen extraction was reduced by saralasin in intact but not in nephrectomized dogs. In six additional experiments, in which blood pressure was not artificially held constant during saralasin infusion, saralasin still significantly improved coronary sinus oxygen saturation and thus reduced coronary oxygen extraction. The data suggest that both hypoxia and the renin-angiotensin system participate in the restriction of metabolic coronary regulation in hemorrhagic shock

Indication of ACE-inhibitors post-myocardial infarction

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril). It remains unsettled, whether or not lower doses are effective. It also remains unclear whether or not other drugs like nitrates may have similar effects. The combination of ACE-inhibitors with β-receptorblockers, thrombolytic therapy and aspirin, respectively, did not prevent the effects of the ACE-inhibitor in the SAVE-study

[Experimental and clinical possibilities of MR spectroscopy of the heart]

MR-spectroscopy of the heart is a relatively new technique for the study of various aspects of cardiac metabolism. The majority of results has so far been obtained with the isolated perfused heart. Here, 31P-MR spectroscopy can be employed to measure high-energy phosphate metabolism and intracellular pH repeatedly and non-invasively. Using a technique called saturation transfer, velocities of enzymatic reactions, such as the creatine kinase reaction, can be measured. Intra- and extracellular Na+ and K+ concentrations can be registered with 23Na- and 39K-MR in conjunction with shift reagent. 13C-MR can be used to tackle carbohydrate metabolism. In-situ-R-spectroscopy allows determination of high-energy phosphates in intact large mammals. Clinical applications of MR-spectroscopy remain to be defined; preliminary results indicate high diagnostic and prognostic potential for patients with coronary artery disease and congestive heart failure

[Indications for ACE inhibitors in the postinfarct period]

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS

Experimental and clinical possibilities of MR spectroscopy of the heart

MR-spectroscopy of the heart is a relatively new technique for the study of various aspects of cardiac metabolism. The majority of results has so far been obtained with the isolated perfused heart. Here, 31P-MR spectroscopy can be employed to measure high-energy phosphate metabolism and intracellular pH repeatedly and non-invasively. Using a technique called saturation transfer, velocities of enzymatic reactions, such as the creatine kinase reaction, can be measured. Intra- and extracellular Na+ and K+ concentrations can be registered with 23Na- and 39K-MR in conjunction with shift reagent. 13C-MR can be used to tackle carbohydrate metabolism. In-situ-R-spectroscopy allows determination of high-energy phosphates in intact large mammals. Clinical applications of MR-spectroscopy remain to be defined; preliminary results indicate high diagnostic and prognostic potential for patients with coronary artery disease and congestive heart failure

Diffusion Imaging of Sport-related Repetitive Head Impacts-A Systematic Review

Repetitive head impacts (RHI) are commonly observed in athletes participating in contact sports such as American football, ice hockey, and soccer. RHI usually do not result in acute symptoms and are therefore often referred to as subclinical or subconcussive head impacts. Epidemiological studies report an association between exposure to RHI and an increased risk for the development of neurodegenerative diseases. Diffusion magnetic resonance imaging (dMRI) has emerged as particularly promising for the detection of subtle alterations in brain microstructure following exposure to sport-related RHI. The purpose of this study was to perform a systematic review of studies investigating the effects of exposure to RHI on brain microstructure using dMRI. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to determine studies that met inclusion and exclusion criteria across three databases. Seventeen studies were identified and critically evaluated. Results from these studies suggest an association between white matter alterations and RHI exposure in youth and young adult athletes. The most consistent finding across studies was lower or decreased fractional anisotropy (FA), a measure of the directionality of the diffusion of water molecules, associated with greater exposure to sport-related RHI. Whether decreased FA is associated with functional outcome (e.g., cognition) in those exposed to RHI is yet to be determined. This review further identified areas of importance for future research to increase the diagnostic and prognostic value of dMRI in RHI and to improve our understanding of the effects of RHI on brain physiology and microstructure

[Indications for ACE inhibitors in the postinfarct period]

Prognosis of patients post-myocardial infarction depends largely on the degree of left ventricular dysfunction, which results from loss of contractile tissue and remodeling of infarcted and surviving myocardium. This remodeling process may result in chronically progressive dysfunction and ultimately in heart failure. Next to mechanical determinants humoral control of hypertrophy, dilatation and qualitative changes of surviving myocardium are discussed. A major determinant of the extent of remodeling is infarct size. Efficacy of angiotensin-converting enzyme (ACE) inhibitors on infarct size was tested in animal experiments with conflicting results. Recent clinical studies also report beneficial (GISSI-3 and ISIS-4) or no (CONSENSUS II) effects on survival post-myocardial infarction when ACE-inhibitors were used in the acute phase. Up to date it remains unsettled which patients may benefit from acute therapy with ACE-inhibitors. Three days after myocardial infarction hemodynamically stable patients with heart failure may be treated with ACE-inhibitors (AIRE study). Prognosis may be improved and manifestation of heart failure prevented or delayed also in patients without heart failure treated in this phase of myocardial infarction with ACE-inhibitors (SAVE study). Prevention of heart failure may also be observed in patients treated later (at least 4 weeks) after myocardial infarction (SOLVD prevention arm). It is essential for this indication that patients are carefully selected for treatment depending on left ventricular function. Duration of treatment in patients with severe left ventricular dysfunction probably has to be lifelong, the doses of ACE-inhibitors used have to be relatively high (e.g. 3 x 50 mg captopril or 2 x 10 mg enalapril).(ABSTRACT TRUNCATED AT 250 WORDS