Traumatic brain injury due to primary blast exposure is a major cause of ongoing neurological and psychological impairment in soldiers and civilians. Animal and human evidence suggests that low-level blast exposure is capable of inducing white matter injury and behavioural deficits. There are currently no effective therapies to treat the underlying suspected pathophysiology of low-level primary blast or concussion. Remote ischemic conditioning (RIC) has been shown to have cardiac, renal and neuro-protective effects in response to brief cycles of ischemia. Here we examined the effects of RIC in two models of blast injury. We used a model of low-level primary blast in rats to evaluate the effects of RIC neurofilament expression. We subsequently used a model of traumatic brain injury in adult zebrafish using pulsed high intensity focused ultrasound (pHIFU) to evaluate the effects of RIC on behavioural outcome and apoptosis in a post-traumatic setting. In blast exposed rats, RIC pretreatment modulated NF200 expression suggesting an innate biological buffering effect. In zebrafish, behavioural deficits and apoptosis due to pHIFU-induced brain injury were reduced following administration of serum derived from RIC rats. The results in the zebrafish model demonstrate the humoral effects of RIC independent of anesthetic effects that were observed in the rat model of injury. Our results indicate that RIC is effective in improving outcome following modeled brain trauma in pre- and post-injury paradigms. The results suggest a potential role for innate biological systems in the protection against pathophysiological processes associated with impairment following shockwave induced trauma.
Vascular endothelial growth factor (VEGF) plays a role in angiogenesis and has been shown to be neuroprotective following central nervous system trauma. In the present study we evaluated the pro-angiogenic and neuroprotective effects of an engineered zinc-finger protein transcription factor transactivator targeting the vascular endothelial growth factor A (VEGF-ZFP). We used two virus delivery systems, adeno-virus and adeno-associated virus, to examine the effects of early and delayed VEGF-A upregulation after brain trauma, respectively. Male Sprague-Dawley rats were subject to a unilateral fluid percussion injury (FPI) of moderate severity (2.2-2.5 atm) followed by intracerebral microinjection of either adenovirus vector (Adv) or an adeno-associated vector (AAV) carrying the VEGF-ZFP construct. Adv-VEGF-ZFP-treated animals had significantly fewer TUNEL positive cells in the injured penumbra of the cortex (p<0.001) and hippocampus (p=0.001) relative to untreated rats at 72 h post-injury. Adv-VEGF-ZFP treatment significantly improved fEPSP values (p=0.007) in the CA1 region relative to injury alone. Treatment with AAV2-VEGF-ZFP resulted in improved post-injury microvascular diameter and improved functional recovery on the balance beam and rotarod task at 30 days post-injury. Collectively, the results provide supportive evidence for the concept of acute and delayed treatment following TBI using VEGF-ZFP to induce angiogenesis, reduce cell death, and enhance functional recovery.
How malleable is alcohol consumption? Specifically, how much is alcohol consumption driven by the current environment versus individual characteristics? To answer this question, we analyze changes in alcohol purchases when consumers move from one state to another in the United States. We find that if a household moves to a state with a higher (lower) average alcohol purchases than the origin state, the household is likely to increase (decrease) its alcohol purchases right after the move. The current environment explains about two-thirds of the differences in alcohol purchases. The adjustment takes place both on the extensive and intensive margins.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.
This paper investigates how Confucianism affects individual decision making in Taiwan and in China.We found that Chinese subjects in our experiments became less accepting of Confucian values, such that they became significantly more risk loving, less loss averse, and more impatient after being primed with Confucianism, whereas Taiwanese subjects became significantly less present-based and were inclined to be more trustworthy after being primed by Confucianism.Combining the evidence from the incentivized laboratory experiments and subjective survey measures, we found evidence that Chinese subjects and Taiwanese subjects reacted differently to Confucianism.
Background: The current standard of care for fluid resuscitation of hemorrhagic hypotensive patients involves the use of crystalloid solutions. Traumatic brain injury (TBI) is often associated with hemorrhage and hypotension, which can contribute significantly to morbidity and mortality. Guidelines for the choice of fluid resuscitation and the use of red blood cell transfusions are not yet clear in the context of brain injury. Methods: Various fluid resuscitation strategies were evaluated in Sprague-Dawley rats using fresh blood, normal saline, hypertonic saline, and albumin fluid resuscitation protocols. Mean arterial blood pressure (MAP) and cerebral oximetry were assessed in hemorrhaged groups and the mean population spike amplitudes (PSA) from the hippocampus were examined in fluid percussion injured (FPI) animals subject to hemorrhage and fluid resuscitation. Results: MAP in control animals, hemorrhage and hemorrhage + albumin treated groups was 82.4 ± 1.5 mm Hg, 55.7 ± 1.5 mm Hg, and 97.0 ± 3.4 mm Hg, respectively. Arterial PaO2 was higher in albumin-treated animals relative to other fluid alternatives. Regional tissue oxygen tension (PbrO2) levels in hemorrhaged animals reached significantly higher levels in albumin treated group compared with in normal saline and hypertonic saline (p < 0.001, p = 0.034, respectively). After FPI+hemorrhage, PSA values in albumin- resuscitated animals were significantly higher than in normal saline-resuscitated animals (p = 0.012). Conclusions: The results of normal saline resuscitation, relative to other fluid alternatives, suggest that a re-evaluation of current treatment strategies in hemorrhagic hypotensive TBI patients is warranted. Albumin demonstrated the greatest beneficial effects on neurophysiology endpoints over crystalloid alternatives. These data suggests that albumin resuscitation may play an important role in the treatment of hemorrhagic hypotension and TBI.
We compare the characteristics and regression coefficients between the participants in a field experiment in China and the survey population from which they were recruited. The experimental participants were more educated, younger, more likely to be male, more risk-loving and work fewer hours than the more general population. The estimates of their regression coefficients in the standard analyses of wages, happiness and entrepreneurship differed significantly from non-participants, indicating that inferences drawn from experimental samples may not hold for more representative groups of the population.
How malleable is alcohol consumption? Specifically, how much is alcohol consumption driven by the current environment versus individual characteristics? To answer this question, we analyze changes in alcohol purchases when consumers move from one state to another in the United States. We find that if a household moves to a state with a higher (lower) average alcohol purchases than the origin state, the household is likely to increase (decrease) its alcohol purchases right after the move. The current environment explains about two-thirds of the differences in alcohol purchases. The adjustment takes place both on the extensive and intensive margins.
