Summary: Free radical-induced oxidative damage reactions, and membrane lipid peroxidation (LP), in particular, are among the best validated secondary injury mechanisms in preclinical traumatic brain injury (TBI) models. In addition to the disruption of the membrane phospholipid architecture, LP results in the formation of cytotoxic aldehyde-containing products that bind to cellular proteins and impair their normal functions. This article reviews the progress of the past three decades in regard to the preclinical discovery and attempted clinical development of antioxidant drugs designed to inhibit free radical-induced LP and its neurotoxic consequences via different mechanisms including the O 2 ⅐Ϫ scavenger superoxide dismutase and the lipid peroxidation inhibitor tirilazad. In addition, various other antioxidant agents that have been shown to have efficacy in preclinical TBI models are briefly presented, such as the LP inhibitors U83836E, resveratrol, curcumin, OPC-14177, and lipoic acid; the iron chelator deferoxamine and the nitroxidecontaining antioxidants, such as ␣-phenyl-tert-butyl nitrone and tempol. A relatively new antioxidant mechanistic strategy for acute TBI is aimed at the scavenging of aldehydic LP byproducts that are highly neurotoxic with "carbonyl scavenging" compounds. Finally, it is proposed that the most effective approach to interrupt posttraumatic oxidative brain damage after TBI might involve the combined treatment with mechanistically complementary antioxidants that simultaneously scavenge LP-initiating free radicals, inhibit LP propagation, and lastly remove neurotoxic LP byproducts.

Mitochondrial dysfunction after traumatic brain injury (TBI) is manifested by increased levels of oxidative damage, loss of respiratory functions and diminished ability to buffer cytosolic calcium. This study investigated the detrimental effects of lipid peroxyl radicals (LOO•) and lipid peroxidation (LP) in brain mitochondria after TBI by examining the protective effects of U-83836E, a potent and selective scavenger of LOO• radicals. Male CF1 mice were subjected to severe controlled cortical impact TBI (CCI-TBI) and treated with either vehicle or U-83836E initiated i.v. at 15 min post-injury. Calcium (Ca++) buffering capacity and respiratory function were measured in isolated cortical mitochondrial samples taken from the ipsilateral hemisphere at 3 and 12 h post-TBI, respectively. In vehicle-treated injured mice, the cortical mitochondrial Ca++ buffering capacity was reduced by 60% at 3 h post-injury (p < 0.001) and the respiratory control ratio was decreased by 27% at 12 h post-TBI, relative to sham, non-injured mice. U-83836E treatment significantly (p < 0.05) preserved Ca++ buffering capacity and attenuated the reduction in respiratory control ratio values. Consistent with the functional effects of U-83836E being as a result of an attenuation of mitochondrial oxidative damage, the compound significantly (p < 0.001) reduced LP-generated 4-hydroxynonenal levels in both cortical homogenates and mitochondria at both 3 and 12 h post-TBI. Unexpectedly, U-83836E also reduced peroxynitrite-generated 3-nitrotyrosine in parallel with the reduction in 4-hydroxynonenal. The results demonstrate that LOO• radicals contribute to secondary brain mitochondrial dysfunction after TBI by propagating LP and protein nitrative damage in cellular and mitochondrial membranes.

Purpose. The study is aimed at exploring the popularity, impact, and usefulness of using YouTube in learning anatomy as perceived by Jordanian medical students studying at Jordan University of Science and Technology. Methods. The present work is a cross-sectional questionnaire-based study. First-, second-, and third-year medical students were invited to complete an anonymous questionnaire. Students’ responses were numerically coded, and the results were analyzed to reveal any statistically significant differences related to gender or level of study. Results. The results showed that 96.4% of the students used YouTube in general, 91.2% used it as a source of information, and 83.9% used YouTube as a learning tool in medical school. Further, YouTube was used by 79.1% of the students as an anatomy-learning tool. Most of these students used this platform in learning gross anatomy. The study also revealed that dissection videos were the most viewed anatomy-related content. Regarding the perceived value of YouTube as an anatomy-learning tool, the majority of the students reported that YouTube offered them useful anatomical information and enhanced their understanding, memorization, and recall of anatomical information. In addition, most of them recommended using YouTube as an anatomy-learning tool. Statistical analysis of the results revealed the presence of gender-related significant differences in students’ perspectives. Such differences were also found among students of different levels of study. Conclusion. Medical students have positive attitudes toward using YouTube in augmenting their anatomy learning. For this, educators are encouraged to adopt YouTube as an educational tool in their anatomy instruction and to create new anatomy-related YouTube videos to enhance their students’ learning.

J. Neurochem. (2011) 117, 579–588. Abstract Free radical‐induced lipid peroxidation (LP) is critical in the evolution of secondary injury following traumatic brain injury (TBI). Previous studies in our laboratory demonstrated that U‐83836E, a potent LP inhibitor, can reduce post‐TBI LP along with an improved maintenance of mouse cortical mitochondrial bioenergetics and calcium (Ca2+) buffering following severe (1.0 mm; 3.5 m/s) controlled cortical impact TBI (CCI‐TBI). Based upon this preservation of a major Ca2+ homeostatic mechanism, we have now performed dose‐response and therapeutic window analyses of the ability of U‐83836E to reduce post‐traumatic calpain‐mediated cytoskeletal (α‐spectrin) proteolysis in ipsilateral cortical homogenates at its 24 h post‐TBI peak. In the dose‐response analysis, mice were treated with a single i.v. dose of vehicle or U‐83836E (0.1, 0.3, 1.3, 3.0, 10.0 or 30.0 mg/kg) at 15 min after injury. U‐83836E produced a dose‐related attenuation of α‐spectrin degradation with the maximal decrease being achieved at 3.0 mg/kg. Next, the therapeutic window was tested by delaying the single 3 mg/kg i.v. dose from 15 min post‐injury out to 1, 3, 6 or 12 h. No reduction in α‐spectrin degradation was observed when the treatment delay was 1 h or longer. However, in a third experiment, we re‐examined the window with repeated U‐83836E dosing (3.0 mg/kg i.v. followed by 10 mg/kg i.p. maintenance doses at 1 and 3 h after the initial i.v. dose) which significantly reduced 24 h α‐α‐spectrin degradation even when treatment initiation was withheld until 12 h post‐TBI. These results demonstrate the relationship between post‐TBI LP, disruptions in neuronal Ca2+ homeostasis and calpain‐mediated cytoskeletal damage.