BackgroundOxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS) following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O2 −), and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI.Methodology/Principal FindingsThe results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24–96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O2 − induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI.Conclusions/SignificanceAs a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

In light of the chemical exploitation of CO 2 , new reusable materials for efficiently catalyzing the cycloaddition of CO 2 and epoxides under moderate conditions are needed. Herein, a new series of isostructural metal−organic frameworks (MOFs) M 2 (EDOB) [EDOB 4− = 4,4′-(ethyne-1,2-diyl)bis(2-oxidobenzoate), M = Mg, Ni, Co, Zn, Cu, Fe], known as M-MOF-184, analogous to a well-studied MOF-74 structure, were synthesized and fully characterized. The M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks exhibit accessible mesopore channels (24 Å) and high porosity. Among them, Mg-MOF-184 demonstrated the most upper surface area (>4000 m 2 g −1 ) in any reported MOF-74-type frameworks. Furthermore, Co-MOF-184 revealed the highest CO 2 uptake (73 cm 3 g −1 , at 298 K), and Zn-MOF-184 showed the highest catalytic activity upon the cycloaddition of CO 2 (96% conversion, 86% selectivity, and 82% yield) under mild conditions (1 atm CO 2 , 80 °C, 6 h, and solvent-free). Notably, the catalytic performance of Zn-MOF-184 outperformed that of the original M-MOF-74 (M = Mg, Co, Zn) materials and various Zn-based MOFs. To evaluate the acidity and basicity of a series of M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks, the interaction of these MOFs with acetonitrile vapor was investigated by vapor adsorption and ATR-FTIR spectroscopy measurements. As such, Zn-MOF-184 showed the strongest Lewis acidity derived by Zn cations, which was correlated to the highest catalytic activity upon the cycloaddition of CO 2 . Interestingly, the 2-oxidobenzoate anions from Co-MOF-184 showed the strongest basicity among the series, which was associated with the highest saturated acetonitrile uptake (544 cm 3 g −1 at 298 K). Our findings suggest that the integration of Lewis acidic and basic sites, high surface area, and large accessible pores into the framework can facilitate the CO 2 fixation reaction.

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A study was undertaken to compare the regeneration of rat peroneal nerves across a 0.5-cm gap repaired with either a permanent, porous or a resorbable, non-porous artificial nerve graft. The resorbable, impermeable artificial nerve graft was a synthetic passive conduit made from polyglycolic acid (PGA). The permanent, porous artificial nerve graft conduit was manufactured from a hydrophilic elastomeric biopolymer (HEB), and four variations were tested. Qualitative histology on short-term animals revealed similar inflammatory reactions to HEB and PGA. Axonal regeneration was evaluated in longer-term animals after three, four, and six months by qualitative and quantitative histology. Qualitative histology on longer-term animals demonstrated both artificial nerve grafts to be anti-immunogenic. All PGA-artificial nerve graft repairs among three-, four-, and six-month rats contained myelinated axons, as did all HEB-1 repairs. However, three other HEB-graft varieties accounted for a 25 percent failed regeneration rate. Quantitative histologic comparison of repair-site cross-sections in viable PGA and HEB matched pairs demonstrated statistically equivalent myelinated axon counts but larger average myelinated fiber diameters in HEB repairs, with p = .001.

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A study was conducted to compare the regeneration across 1.4-cm peroneal nerve gaps in rats, repaired with sutured autografts or with artificial nerve grafts. The artificial models were composed of a biodegradable passive conduit made of glycolide trimethylene carbonate, filled with either phosphate-buffered saline or a collagen extracellular matrix. Functional recovery was evaluated by walking track analysis throughout the experiment. After 9 months, the nerves were analyzed by electrophysiology and by qualitative and quantitative histology. Walking track analysis demonstrated the three repair methods to provide statistically equivalent recovery, except at day 195 post-engraftment, when the collagen-filled conduit was superior to the saline-filled conduit. Electrophysiologically, the autograft was superior to the collagen-filled conduit, while the collagen- and saline-filled conduits were equivalent. Quantitative histology demonstrated that normal intact nerve had larger mean myelinated axonal diameters but an equal number of axons to the three repair methods, and that the repair methods were statistically equivalent. While the repair methods had similar histologic and functional outcomes, combined standardized scoring demonstrated that the autograft was superior to the statistically-equivalent entubulation repairs. A collagen gel may serve as an ideal matrix in which to suspend neurotrop(h)ic factors or cells.

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A study was designed to determine whether a completely sutureless technique of nerve repair using avitene and polyglycolic acid (PGA) tube could provide a better repair than the standard suture repair technique. Randomized peroneal nerves of 18 male Sprague-Dawley rats were used. The study was divided into two parts. The first part was designed to test the adhesive and tensile strength of avitene at the second postoperative day in seven animals. The tensile strength of the suture repair at 498 mN +/- 130 was found to be statistically equivalent (p = 0.77) to the repair using avitene and PGA tube at 474 mN +/- 192. The second part of the study evaluated axonal regeneration in 11 animals. Evaluation by electrophysiology revealed a significant difference (p = 0.05) between the mean percentage of Integrated Mean Compound Action Potential for the suture repaired nerve (53.1 +/- 17.6 percent) and that of the avitene and PGA tube repaired nerve (72.0 +/- 17.9). The mean axonal count and mean fiber diameter for the suture repair technique (1,879 +/- 225 and 4.3 +/- 0.4 microns, respectively) were not significantly different (p = 0.61 and 0.67, respectively) from those of the avitene-PGA tube repair technique (1,938 +/- 398 and 4.2 +/- 0.4 microns, respectively).