Blast-induced traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and in training sites with long-term neurological and psychological pathologies. Previous studies from our laboratory demonstrated activation of oxidative stress pathways after blast injury, but their distribution among different brain regions and their impact on the pathogenesis of bTBI have not been explored. The present study examined the protein expression of two isoforms: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 (NOX1, NOX2), corresponding superoxide production, a downstream event of NOX activation, and the extent of lipid peroxidation adducts of 4-hydroxynonenal (4HNE) to a range of proteins. Brain injury was evaluated 4 h after the shock-wave exposure, and immunofluorescence signal quantification was performed in different brain regions. Expression of NOX isoforms displayed a differential increase in various brain regions: in hippocampus and thalamus, there was the highest increase of NOX1, whereas in the frontal cortex, there was the highest increase of NOX2 expression. Cell-specific analysis of changes in NOX expression with respect to corresponding controls revealed that blast resulted in a higher increase of NOX1 and NOX 2 levels in neurons compared with astrocytes and microglia. Blast exposure also resulted in increased superoxide levels in different brain regions, and such changes were reflected in 4HNE protein adduct formation. Collectively, this study demonstrates that primary blast TBI induces upregulation of NADPH oxidase isoforms in different regions of the brain parenchyma and that neurons appear to be at higher risk for oxidative damage compared with other neural cells.

Objective. Cerebral autoregulation is critically important to maintain proper brain perfusion and supply the brain with oxygenated blood. Non-invasive measures of blood pressure (BP) are critical in assessing cerebral autoregulation. Wave propagation velocity may be a useful technique to estimate BP but the effect of the location of the sensors on the readings has not been thoroughly examined. In this paper, we were interested in studying whether the propagation velocity of a pressure wave in the direction from the heart to the brain may differ compared with propagation from the heart to the periphery, as well as across different physiological tasks and/or health conditions. Using non-invasive sensors simultaneously placed at different locations of the human body allows for the study of how the propagation velocity of the pressure wave, based on pulse transit time (PTT), varies across different directions. Approach. We present a multi-sensor BP wave propagation measurement setup intended for cerebral autoregulation studies. The presented sensor setup consists of three sensors, one placed on each of the neck, chest and finger, allowing simultaneous measurement of changes in BP propagation velocity towards the brain and to the periphery. We show how commonly tested physiological tasks affect the relative changes of PTT and correlations with BP. Main results. We observed that during maximal blow, valsalva and breath hold breathing tasks, the relative changes of PTT were higher when PTT was measured in the direction from the heart to the brain than from the heart to the peripherals. In contrast, during a deep breathing task, the relative change in PTT from the heart to the brain was lower. In addition, we present a short literature review of the PTT methods used in brain research. Significance. These preliminary data suggest that the physiological task and direction of PTT measurement may affect relative PTT changes. The presented three-sensor setup provides an easy and neuroimaging compatible method for cerebral autoregulation studies by allowing measurement of BP wave propagation velocity towards the brain versus towards the periphery.

Cerebral autoregulation is an important mechanism to protect the brain by maintaining the brain perfusion over varying blood pressures. The cerebral blood flow velocity response to Sit‐To‐ Stand maneuver has been widely used to assess dynamic cerebral autoregulation. Previous work has demonstrated sex differences in autoregulation; however, little is known about the impact of race. Potential racial differences in cerebral autoregulation may contribute to different incidences of cerebrovascular events between different races. Therefore, the purpose of this study was to compare the Autoregulatory index between four different racial groups. We enrolled 55 young healthy subjects (aged 18~35 years) with four racial groups, i.e. White/Caucasian (Age 27±5; n=11; 5 Males), Black/African American (Age 28±6; n=8; 4 Males), Latino (Age 28±6; n=6; 2 Males), and Asian (Age 27±3; n=30; 15 Males). The transcranial Doppler was used to continuously record the cerebral blood flow velocity at middle cerebral artery during 3 repeated sit‐to‐stand maneuvers, with simultaneous measurements of blood pressure, heart rate, and end‐tidal CO2 (ETCO2). There was no difference in demographic variables across groups except for BMI (24±4, 26±4, 27±5, and 23±3; kg/m2, P=0.043). Similarly, there were no differences in baseline cerebral blood flow velocity, blood pressure or heart rate with the exception of ETCO2 (35±3, 40±4, 35±3, and 38±3 mmHg, P=0.003). We found no differences between groups in the physiological response during sit‐to‐stand. Similarly, autoregulatory index was similar across all racial groups (3.6±2.4, 3.9±1.2, 3.3±2.6, and 3.6±1.5, P=0.948). These data suggest that cerebral autoregulation is similar in young healthy individuals across different races. However, these findings must be interpreted with caution due to the small number of participants in the various racial groups. Future studies are warranted to include larger sample size, older subjects and also to consider sex differences within each race. Support or Funding Information Supported by the Funding from Rutgers University and U.S. Department of Defense.

Sports related concussion is estimated to affect more than 3.8 million Americans a year. Despite the large number of concussions, our understanding of the mechanisms underlying concussion are limited. We also lack an accurate diagnostic tool to provide an indication of concussion severity. Currently, most concussion assessments use cognitive testing to assess severity. Our lab has been examining use of Doppler ultrasound in the field as a possible novel objective measures of concussion severity. We recruited players from recreational rugby tournaments. Players who were seen at the medical tent and determined not to need further treatment were offered the opportunity to participate. A control group of players who had played a rugby match but did not receive a head hit were also recruited. During the tournaments, we used a portable tent based lab to obtain measures of internal carotid cerebral blood flow by imaging the artery to obtain diameter and velocity. Additionally, we measured both beat‐by‐beat blood pressure (Finometer) as well as end tidal CO2 using a nasal cannula during rest, both in the seated and supine position. In a subgroup of 47 players (28 controls, 19 concussed, Mean age= 30, range= 19–66 yrs) out of our large study (125 players, 49 concussed), we had players perform a Simple Reaction Time Test (SRTT), Trails A & B, Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) with 3 sec and 2 sec delay and a Digit Span Memory Test. Concussed players had significantly higher SCAT total number of symptoms (15 ± 11 vs 5 ± 7, P=0.029) as well as Symptom Severity Score (33 ± 18 vs 7 ± 9, P=0.002). Concussed players only performed significantly worse on the SRTT (353 ± 128 ms vs 278 ± 44 ms, P=0.046) while trending on DSST (54 ± 15 ms vs 63± 4 ms, P=0.085). Concussed players demonstrated significantly greater cerebral blood flow when seated (646 ± 180 mL/min vs 415 ± 85 mL/min, P=0.001). Cerebral blood flow was also significantly correlated to performance on SRTT (r=0.84, P=0.035), Trails B Time (r=0.94, P=0.006), DSST (r=−0.88, P=0.021) and Digit Span (r=−0.89, P=0.019). Surprisingly increased seated cerebral blood flow was found in the concussed players and associated with worse cognitive performance. This initial study suggests that cerebral blood flow immediately post‐concussion may be an objective indicator of severity. Future work is needed to examine how immediate measures of cerebral blood flow are predictive of cognitive recovery and post‐concussive symptoms.Support or Funding InformationThis work was supported by Dept. of Pharmacology, Physiology, and Neuroscience, Rutgers and the War Related Illness and Injury Study Center.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background Higher cerebral blood flow (CBF) pulsatility was found to be associated with severer brain white matter lesions in the elderly [1]. It was hypothesized that the central/elastic arterial stiffness/compliance may directly affect CBF pulsatility. However, it is still unclear which carotid stiffness parameters may better reflect this impact, and whether race and sex differences are present. Methods To study the correlations among those parameters with comparisons between different races and sexes, we enrolled 35 young healthy subjects (19 females), aged 29 ± 5 (18~40) years, with three races of comparable age and sex ratio, i.e. White (n = 16), Black (n = 7), and Asian (n = 12). All subjects were in resting seated position, with continuous transcranial Doppler recording of CBF velocity at middle cerebral artery (MCA), simultaneous 1-min ultrasound echo-tracking on bilateral common carotid arteries, and multiple measurements of brachial blood pressure (BP). Results All derived parameters [2], including MCA pulsatility index (PI), showed no significant racial differences but with significantly (p < 0.05) higher carotid stiffness index (β), Peterson’s pressure modulus (Ep), BP pulsatility index (mostly driven by higher systolic BP but similar diastolic BP), and lower arterial compliance (AC, p = 0.07) in males than in females. Only AC (but not β and Ep) showed a significant correlation with PI (r = 0.49, p = 0.004) even after controlling for BP pulsatility index, which negatively correlated with AC (β = −0.35, p = 0.038). Conclusions Higher carotid AC (i.e. decreased stiffness) seems to enhance CBF pulsatility in young healthy populations, which might differ from the elderly.