Exogenous Intervention Research Articles

Relative Performance Evaluation, Sabotage and Collusion

Relative performance evaluation (“RPE”) is a useful tool for shielding risk averse agents from systematic uncertainty. However, RPE can also destroy firm value by encouraging executives to implement excessively aggressive product market strategies to improve their relative standing through costly sabotage. We posit that explicit collusion restricts a firm’s ability to engage in sabotage, thereby improving the net benefits of RPE. Consistent with this hypothesis, we document that: (1) cartel members are more likely to use RPE, especially in more concentrated markets; (2) conditional on using RPE, cartel members include more economically similar firms in their peer group; (3) firms are disproportionately likely to drop RPE from their executives’ pay package within one year of their cartel being dissolved by a plausibly exogenous intervention; and (4) RPE is associated with greater product market aggression, but only among non-cartel firms. Collectively, our evidence suggests that the potential for costly sabotage is an important deterrent to firms’ reliance on RPE, and that explicit collusion mitigates this effect, thereby facilitating more efficient risk-sharing.

Pharmacologic Activation of Aldehyde Metabolism to Protect Hematopoietic Stem Cells (HSC) in Murine Models of Fanconi Anemia (FA)

HSC loss in FA is due to failure to resolve DNA inter-strand crosslinks (ICL), which can be induced by reactive aldehydes, radiation, or other clastogenic agents. Aldehyde exposure may occur through environmental sources, e.g. ingestion, absorption, and inhalation, or endogenously as a byproduct of cellular metabolism. The ALDH2*2 genotype, a dominant-negative point mutation in the aldehyde dehydrogenase 2 (ALDH2) gene, causes the "Asian flushing syndrome" when ethanol (EtOH) is ingested, due to decreased metabolism of small aldehydes, particularly acetaldehyde. ALDH2*2 is a disease modifier in FA, causing more rapid bone marrow failure and earlier leukemia onset in doubly affected children. Similarly, mice experimentally doubly knocked out for FANCD2 and ALDH2 demonstrate increased HSC loss, which is accelerated by EtOH exposure. To reduce aldehyde exposure, we developed a small molecule ALDH activator, Alda-1, which increases the enzymatic activity of both wild type (WT) and mutant ALDH2. We hypothesized that DNA damage and HSC loss in FA would be prevented by reduction of the aldehyde load. To test the effects of Alda-1 mediated ALDH2 activation, we generated a novel murine FA model with FANCD2 KO and knock-in of the ALDH2*2 mutation into the murine locus. The FANCD2-/- ALDH2*1/*2 genetic model and parental controls were then tested after exogenous aldehydic challenge and/or therapeutic intervention with Alda-1. Increased aldehydic load was experimentally induced by EtOH administration 10 mg/kg/day IP, while Alda-1 10 ug/kg/day was continuously administered via osmotic pump. For each of these conditions, marrow was analyzed for HSC and progenitor cell (HSPC) number, HSC gene expression, and function. The importance of the altered aldehyde metabolism due to ALDH2*2 genotype was demonstrated by progressive loss of HSPC in ALDH2*2/*2 and FANCD2-/- ALDH2*1/*2 mice, e.g., 5-fold and 2-fold decline in long-term HSC (LT-HSC), respectively, by 36 weeks. Experimental EtOH challenge to increase the aldehyde load precipitously decreased HSC numbers of all genotypes. After 5 weeks of EtOH challenge, LT-HSC decreased 35-fold in FANCD2-/- ALDH2*1/*2, 12.5-fold in FANCD2-/-ALDH2*1/*1, and 10.5-fold in WT mice. Long-term Alda-1 treatment to decrease aldehydic load rescued FA mice from HSC loss. After 7 months of Alda-1 treatment, LT-HSC numbers in FANCD2-/-ALDH2*1/*2 and FANCD2-/-ALDH2*1/*1 were approximately 10-fold higher than untreated controls. There were no clinically observed adverse effects. Aldehyde exposure and Alda-1 treatment altered gene expression of HSC. Principal component analysis and clustering of HSC gene expression showed that the first principal component representing 40% of the variation in gene expression could be attributed to increased aldehydic load, either genetically (ALDH2*2 genotype) or environmentally (EtOH administration) induced, while Alda-1 treatment obviated these effects. HSC from Alda-1 treated mice clustered with those from control WT mice. To test whether Alda-1 improved HSC function as well as phenotypic number, engraftment potential was assessed with competitive repopulation assays of sorted HSC from congenic untreated donors vs short-term (3 weeks) Alda-1 treated donors. HSC from Alda-1 treated mice had 2-4 fold greater granulocyte repopulating capacity than those from the untreated donors. Our results demonstrate that Alda-1 treatment rescues HSC from aldehyde induced loss, whether from genetic variation (FANCD2- and/or ALDH2*2) or experimental challenge (EtOH administration). Furthermore, Alda-1 treatment prevents the abnormal HSC gene expression induced by increased aldehydic load. HSC function is improved by Alda-1 with greater repopulating capacity observed even after short-term treatment. These preclinical experiments provide compelling proof-of-concept that sustained activation of ALDH2 can prevent HSC loss in FA. Potential applications include long-term administration to prevent the development of marrow failure or leukemia, and HSC expansion to increase the number of cells available for gene therapy with autologous HSC. Our results suggest that a clinical trial of ALDH2 activation in FA patients to prevent marrow failure is warranted. Disclosures Van Wassenhove: U.S. Patent Office: Patents & Royalties: patent pending - submitted for ALDH2 activators to expand hematopoietic stem cells. Chen:Foresee Pharmaceuticals: Patents & Royalties: patents licensed to Foresee related to compounds that activate aldehyde dehydrogenase 2 (ALDH2) and correct the dysfunction in ALDH2*2; U.S. Patent Office: Patents & Royalties: patent pending - submitted for aldehyde dehydrogenase 2 (ALDH2) activators to expand hematopoietic stem cells. Mochly-Rosen:Foresee Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: patents licensed to Foresee related to compounds that activate aldehyde dehydrogenase 2 (ALDH2) and correct the dysfunction in ALDH2*2; U.S. Patent Office: Patents & Royalties: patent pending - submitted for aldehyde dehydrogenase 2 (ALDH2) activators to expand hematopoietic stem cells. Weinberg:U.S. Patent Office: Patents & Royalties: patent pending - submitted for aldehyde dehydrogenase 2 (ALDH2) activators to expand hematopoietic stem cells.

Social influences in cross-border entrepreneurial migration policy

This paper addresses the possibilities for public policy to stimulate the entrepreneurial perceptions of individuals by leveraging micro-level social influences produced by migrant entrepreneurs. As opposed to the conventional stand according to which entrepreneurial ecosystems can be stimulated by financial, regulative, cognitive and normative mechanisms of influence, the present study suggests that socio-psychological influences enacted by exogenous policy intervention can be used as a mechanism for shifting the entrepreneurial perceptions of individuals. Cross-border entrepreneurial migration is proposed as an instrument for enacting these socio-psychological influences and enabling public policy to benefit from the distinctively different entrepreneurial behaviors of migrant entrepreneurs and local individuals in the host country. The study offers substantial policy implications by extending the theoretical reasoning guiding the stimulation of entrepreneurial ecosystems through public policy intervention, providing discussion of opportunity perception in cross-border context, and offering an alternative socio-economic perspective on the role of migrant entrepreneurs in the economic life of host countries.

Enhanced “contact mechanism” for interaction of extracellular polymeric substances with low-grade copper-bearing sulfide ore in bioleaching by moderately thermophilic Acidithiobacillus caldus

In order to enhance the “contact mechanism” governing the interaction of extracellular polymeric substances (EPS) with low-grade copper-bearing sulfide ore for the bioleaching of copper, moderately thermophilic Acidithiobacillus caldus was subjected to exogenous intervention with iron and sulfur. The enhancement of the contact mechanism was systematically investigated by evaluating the attached cells/EPS dynamics, intracellular adenosine triphosphate (ATP), cell functional groups, gene transcriptional level, and ore characteristics. Confocal laser scanning microscopy (CLSM) revealed that exogenous intervention with iron and sulfur led to the production of a denser EPS layer and faster adsorption of the attached cells to the ore based on differential fluorescence staining, which indicated enhancement of the “contact mechanism”. The increased intracellular ATP content of the attached cells in the exogenous substrate system provided the required energy for the adsorption processes associated with the “contact mechanism”. Fourier-transform infrared spectroscopic (FTIR) analysis of the attached cells and the ore showed a dramatic shift of the NH and COS peaks (associated with EPS formation), whereas the FTIR peaks of SO and SO42− associated with sulfur metabolism were also significantly influenced. Moreover, reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that the expression of genes related to cellular energy metabolism (nuoB, nuoC, atpE, atpF), sulfur metabolism (sor, sqr, sdo, soxA), biofilm formation (pgaA, pgaB), and cell colonization (acfA, acfB, acfC, acfD) was up-regulated after exogenous intervention, verifying enhancement of the “contact mechanism” at the transcriptional level. In addition, scanning electron microscopy (SEM) indicated more obvious adsorption traces on the ore surface. X-ray diffraction (XRD) indicated the presence of more complex derivatives, such as Fe3(SO4)4, FeSO4, Fe2(SO4)3, and Cu2S, which is suggestive of more active iron/sulfur metabolism with addition of the exogenous iron and sulfur. Overall, a model for bioleaching of low-grade copper-bearing sulfide ore by moderately thermophilic A. caldus was constructed. The results of this investigation should provide a guide for similar industrial bioleaching processes.

Stabilizing Endogenous Instability: Proposals for An Institutionalist Reform of Financial Regulation

:A major and persistent question behind economic theories and related policies is whether the market can self-regulate without any restrictive exogenous intervention or whether regular and binding public regulation is necessary for ensuring the reproduction of the economic system in a sustainable way over time. This article considers this question with regard to the working of financial markets in a liberalized environment. Drawing upon an institutionalist stance, the article shows why the operation of a financialized capitalist economy usually leads to systemic imbalances and crises. The article then suggests an alternative framework for a consistent financial regulation that could prevent market actors from developing short-sighted strategies and gambling on macro stability.

Indecent proposals: Estimating the impact of regional state aid through EU guideline compliance

This paper estimates the causal effects of Flanders' main industrial policy programme, aiming to support economic development in lagging municipalities. The identification strategy exploits a State Aid reform which required Member States to propose a designation methodology and a selection of eligible municipalities in accordance with the new guidelines. While the proposed designation indicators allow us to account for selection on observables, further compliance with State Aid guidelines make causal inference possible. Additionally, we exploit exogenous intervention in the selection of municipalities, as the first regional aid map was not accepted by the European Commission. We find strong evidence for a 10% effect on manufacturing employment, largely explained by jobs safeguarded in declining industries.

Exogenous intervention with sodium hydrosulfite enhances the quality of Radix Scutellariae by modulating antioxidases and secondary metabolites

Introduction: The transformation of wild herbal medicine into cultivation results in decreased quality, becoming an issue of concern in China, even has a word, “traditional Chinese medical science would be destroyed by herbal medicine.” Now, there is no way to acquire superior herb medicine. Reactive oxygen species (ROS) are generated under stress and represent key plant products that induce secondary metabolism. ROS may be important intermediates that link environmental stress to secondary metabolism. Sodium hydrosulfite (Na2S2O4) is just one compound that produces O2•-. Materials and Methods: The fresh roots of Scutellaria baicalensis were treated with 0.0004, 0.04, and 4 mmol/L Na2S2O4, respectively. A stress model was established to elucidate the change of secondary metabolism, antioxidant enzyme system, and enzymes relating to flavonoids. Results: Na2S2O4regulated the activities of β-glucuronidase (GUS) and UDP-glucuronate baicalein 7-O-glucuronosyltransferase (UBGAT) and promoted the transformation of flavonoid glycosides into aglycones with greater antioxidant capacities. In fresh S. baicalensis roots, Na2S2O4decreased the activities of superoxide dismutase, catalase, and peroxidase (POD), which led to a substantial accumulation of hydrogen peroxide (H2O2). H2O2increased the expression of phenylalanine ammonia lyase, GUS, and UBGAT genes and promoted the synthesis and transformation of flavonoids. Moreover, polyphenol oxidase regulated the flavonoid content to maintain the oxidation balance. Although the content of flavonoid glycosides was slightly reduced, the total flavonoid content remained high. Notably, the content of baicalein, an antioxidant compound, increased from 0.28% to 1.96%. Conclusions: ROS facilitated the dominant role of secondary metabolites and enhanced the quality of Radix Scutellariae. Abbreviations used: APX: Ascorbate peroxidase, CAT: Catalase, GUS: β-glucuronidase, PAL: Phenylalanine ammonia lyase, POD: Peroxidase, PPO: Polyphenol oxidase, ROS: Reactive oxygen species, SOD: Superoxide dismutase, UBGAT: UDP-glucuronate baicalein 7-O-glucuronosyltransferase.

The “Beeching Axe” and electoral support in Britain

Policy implementation has important electoral effects, but there is often a problem in determining if policy changes drive electoral behaviour or if the process works in reverse. To address this issue we exploit a unique natural experiment in Britain: the closure of thousands of train stations, known as the Beeching Cuts, on the eve of General Election of 1964. We use several statistical methods to show that policy implementation was unaffected by partisan considerations and therefore it can be regarded as an exogenous intervention. An individual level model of voting intentions from the first British Election Study conducted in 1963, and an aggregate model of party vote shares in the General Election of 1964 show that the closures significantly changed voting support for the Conservative party. The 1964 election was very competitive and the closures clearly contributed to the defeat of the incumbent government after 13 years of uninterrupted rule.

Addressing complexity in population health intervention research: the context/intervention interface

BackgroundPublic health interventions are increasingly being recognised as complex and context dependent. Related to this is the need for a systemic and dynamic conception of interventions that raises the question...

Complementarity and substitution between physical and virtual travel for instrumental information sharing in remote rural regions: A social network approach

International development practitioners are highly optimistic that mobile phones can improve the lives of the inhabitants of remote rural areas in developing countries with an underdeveloped transportation infrastructure. However, the instrumental role of telecommunication is unclear in contexts where residents’ information-sharing networks are strongly geographically constrained by their limited mobility. Empirical research on the interactions between telecommunication and travel in rural areas of developing countries is lacking.This study analyses physical and virtual contact patterns within 1270 instrumental information-sharing relationships reported by the inhabitants of the Pulau Panggung and Sumber Rejo rural subdistricts of Indonesia. In 2013, we implemented an exogenous mobility intervention. In 2014, we administered a network survey in 16 randomly selected farming groups to map local residents’ egocentric and sociocentric physical and virtual travel networks.By comparing the observed networks with simulated random networks, analysing the relationship characteristics and their history, and performing a regression analysis with fixed effects, we examine the complementarity and substitution between telecommunication and travel in the creation and maintenance of social networks. By examining the effects of the exogenous intervention, we can explain the mechanisms underlying the uncovered associations.The results suggest path dependency between physical and virtual travel in remote rural areas. The implication for transportation policy is that physical mobility is a precondition for the creation of virtual information-sharing links. Instrumental communication relationships that do not socially require regular physical co-presence can be partially substituted by virtual travel only after virtual links have been created through physical mobility. Therefore, in contrast with general expectations, mobile telephony in remote rural regions is more practical if the transportation infrastructure is adequately developed. The paper concludes with a discussion of the potential contribution of the sociocentric network perspective to transportation research.

Predicting the popularity growth of online content: Model and algorithm

The evolution of the popularity of online content is analyzed, and two characteristic patterns pertaining to linear and non-linear growth periods are detected. While the former characterizes the propagation of online content through a dynamical process in a state of statistical equilibrium, the latter appears when this state is perturbed by exogenous intervention events. Such episodes increase the susceptibility of higher threshold individuals who opportunistically adopt the propagating content. To capture the dynamics of both diffusion modes, the popularity of online content is modeled by interlacing linear and non-linear growth terms, reduced to 1st-degree polynomial and logistic functions corresponding respectively to stationary and non-stationary adoption phases. The precise fit of the model to empirical popularity patterns verifies its suitability as prediction tool. The proposed model is employed to generate forecasts about the popularity of online content through extrapolation. Highly accurate prediction results surpassing existing methods in terms of precision and predictive capacity are demonstrated. The prediction method is formulated into an algorithm, applicable to real time forecasting of the popularity of online content without training, using minimal, macroscopic, publicly available information.

Narratives of Development

AbstractThe Chaguanas Borough Corporation in Trinidad and Tobago is currently the fastest-growing borough where economic development is complemented by investment in residential, commercial and infrastructural programmes. In tandem with the local government, an inter-governmental organisation (IGO) sought to understand the sociohistorical context within which economic growth has taken place to inform the IGO’s development plans for the area. This article focuses on local narratives collected in 2013 as part of a historical case study that reveals a complex relationship of citizens to the state within the context of a post-colonial, multi-ethnic society. Using an interpretivist framework of narratives as language, metaphor and knowledge, I examine how narratives reflect the lived experience of economic development as a confluence of history, ethnic identity and neoliberal ideas of entrepreneurship. Their inclusion as a source of enquiry in development planning will ensure that exogenous intervention remains holistic, equitable and informed by historical institutions of social practice.

An agent based decentralized matching macroeconomic model

In this paper we present a macroeconomic microfounded framework with heterogeneous agents—individuals, firms, banks—which interact through a decentralized matching process presenting common features across four markets—goods, labor, credit and deposit. We study the dynamics of the model by means of computer simulation. Some macroeconomic properties emerge such as endogenous business cycles, nominal GDP growth, unemployment rate fluctuations, the Phillips curve, leverage cycles and credit constraints, bank defaults and financial instability, and the importance of government as an acyclical sector which stabilize the economy. The model highlights that even extended crises can endogenously emerge. In these cases, the system may remain trapped in a large unemployment status, without the possibility to quickly recover unless an exogenous intervention takes place.

Brain's reward circuits mediate itch relief. a functional MRI study of active scratching.

Previous brain imaging studies investigating the brain processing of scratching used an exogenous intervention mimicking scratching, performed not by the subjects themselves, but delivered by an investigator. In real life, scratching is a conscious, voluntary, controlled motor response to itching, which is directed to the perceived site of distress. In this study we aimed to visualize in real-time by brain imaging the core mechanisms of the itch-scratch cycle when scratching was performed by subjects themselves. Secondly, we aimed to assess the correlations between brain patterns of activation and psychophysical ratings of itch relief or pleasurability of scratching. We also compared the patterns of brain activity evoked by self-scratching vs. passive scratching. We used a robust tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to motion artifacts: 3D gradient echo and spin echo (GRASE) - Propeller. Active scratching was accompanied by a higher pleasurability and induced a more pronounced deactivation of the anterior cingulate cortex and insula, in comparison with passive scratching. A significant involvement of the reward system including the ventral tegmentum of the midbrain, coupled with a mechanism deactivating the periaqueductal gray matter (PAG), suggests that itch modulation operates in reverse to the mechanism known to suppress pain. Our findings not only confirm a role for the central networks processing reward in the pleasurable aspects of scratching, but also suggest they play a role in mediating itch relief.

Maternal supplementation of nucleotides improves the behavioral development of prenatal ethanol-exposed mice

Maternal ethanol consumption during pregnancy can induce learning deficits in the offspring. The objective of this study was to assess whether supplementation of exogenous nucleotides during pregnancy and lactation would ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, and to explore the possible mechanisms. In the present study, pregnant C57BL/6J mice were exposed to ethanol (5 g/kg body weight) intragastrically from gestational day (GD) 6 to GD15. The dams in exogenous nucleotide intervention groups were fed with feed containing 0.01%, 0.04%, or 0.16% nucleotide powder, with control and ethanol groups receiving normal feed. The dams were allowed to deliver naturally and to breast feed their offspring. After weaning, behavioral tests were carried out in the offspring of each group. Serum oxidation indexes were analyzed, and the hippocampus of each offspring was collected and detected for acetyl cholinesterase (AChE) activity and the expression of p-CREB, CREB, and BDNF. The results showed that maternal supplementation with exogenous nucleotides during pregnancy could ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, through improving their antioxidant capacity, reversing hippocampus AChE levels, and allowing the expression of some proteins related to learning and memory. However, different sensitivities were found between the two sexes.

Insulin and the Brain

Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.

An Agent-Based Decentralized Matching Macroeconomic Model

In this paper we present a macroeconomic microfounded framework with heterogeneous agents -- households, firms, banks -- which interact through a decentralized matching process presenting common features across four markets -- goods, labor, credit and deposit. We study the dynamics of the model by means of computer simulation. Some macroeconomic properties emerge such as endogenous business cycles, nominal GDP growth, unemployment rate fluctuations, the Phillips curve, leverage cycles and credit constraints, bank defaults and financial instability, and the importance of government as an acyclical sector which stabilize the economy. The model highlights that even extended crises can endogenously emerge. In these cases, the system may remain trapped in a large unemployment status, without the possibility to quickly recover unless an exogenous intervention.

Driving Ge Island Ordering on Nanostructured Si surfaces

Semiconductor epitaxial nanostructures have been recently proposed as the key building blocks of many innovative applications in materials science and technology. To bring their tremendous potential to fruition, a fine control of nanostructure size and placement is necessary. We present a detailed investigation of the self-ordering process in the prototype case of Ge/Si heteroepitaxy. Starting from a bottom-up strategy (step-bunching instabilities), our analysis moves to lithographic techniques (scanning tunneling lithography, nanomechanical stamping, focused ion beam patterning) with the aim of developing a hybrid approach in which the exogenous intervention is specifically designed to suit and harness the natural self-organization dynamics of the system.

Robust CNS regeneration after complete spinal cord transection using aligned poly- l-lactic acid microfibers

Following spinal cord injury, axons fail to regenerate without exogenous intervention. In this study we report that aligned microfiber-based grafts foster robust regeneration of vascularized CNS tissue. Film, random, and aligned microfiber-based conduits were grafted into a 3 mm thoracic rat spinal cord gap created by complete transection. Over the course of 4 weeks, microtopography presented by aligned or random poly- l-lactic acid microfibers facilitated infiltration of host tissue, and the initial 3 mm gap was closed by endogenous cell populations. This bulk tissue response was composed of regenerating axons accompanied by morphologically aligned astrocytes. Aligned fibers promoted long distance (2055 ± 150 μm), rostrocaudal axonal regeneration, significantly greater than random fiber (1162 ± 87 μm) and film (413 ± 199 μm) controls. Retrograde tracing indicated that regenerating axons originated from propriospinal neurons of the rostral spinal cord, and supraspinal neurons of the reticular formation, red nucleus, raphe and vestibular nuclei. Our findings outline a form of regeneration within the central nervous system that holds important implications for regeneration biology.

Preclinical use of longitudinal MRI for screening the efficacy of s‐nitrosoglutathione in treating spinal cord injury

To evaluate the therapeutic efficacy of S-nitrosoglutathione (GSNO) in spinal cord injury (SCI) using in vivo MRI in combination with neuorobehavioral testing and postmortem tissue analysis. Sixteen female rats were mildly injured at the vertebral T10 level and randomized into control (n = 8) and GSNO-treatment (n = 8) groups. GSNO was delivered at 0.05 mg/kg dose in saline by means of tail vein at 1 hr postinjury and then given orally on the following days. On postinjury days 1, 3, 7, and 28, the rats were tested behaviorally, then scanned using sagittal T2-weighted MRI for the quantification of lesion, edema, and hemorrhagic regions at the injury site. Excised cords were analyzed using histology and immunohistochemistry. Treatment with GSNO was feasible in rats with SCI. On the average, the GSNO group at each scan day 1, 3, 7, and 28 exhibited better functional recovery as indicated by the behavioral performance of 52%, 33%, 19%, and 18%, and had smaller lesions of -4%, -16%, -20%, and -17% compared with the controls, respectively. Edema trend was parallel to the lesion volumes in both groups. Ex vivo data demonstrated that GSNO plays a role in neuronal tissue preservation and sparing. The data collectively provided the preliminary evidence that the injured rats responded favorably to GSNO treatment. Longitudinal MRI provides critical quantitative information regarding the changes in lesion properties, which helps evaluating the efficacy of an exogenous intervention in SCI.