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Prized for their ability to generate chemical complexity rapidly, catalytic carbon-hydrogen (C-H) activation and functionalization reactions have enabled a paradigm shift in the standard logic of synthetic chemistry. Directing group strategies have been used extensively in C-H activation reactions to control regio- and enantioselectivity with transition metal catalysts. However, current methods rely heavily on coordination with nitrogen and/or oxygen atoms in molecules and have therefore been found to exhibit limited generality in asymmetric syntheses. Here, we report enantioselective C-H activation with unsaturated hydrocarbons directed by phosphorus centres to rapidly construct libraries of axially chiral phosphines through dynamic kinetic resolution. High reactivity and enantioselectivity are derived from modular assembly of an iridium catalyst with an endogenous phosphorus atom and an exogenous chiral phosphorus ligand, as confirmed by detailed experimental and computational studies. This reaction mode significantly expands the pool of enantiomerically enriched functional phosphines, some of which have shown excellent efficiency for asymmetric catalysis.
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Subarachnoid hemorrhage (SAH) is a neurological emergency characterized by dysfunctional inflammatory response. However, no effective therapeutic options have been reported so far. Microglia polarization has been proposed to exert an essential role in modulating inflammatory response after SAH. Sestrin2 is a stress response protein. Growing evidence has reported that sestrin2 could inhibit M1 microglia and promote M2 microglia polarization. The current study investigated the effects of sestrin2 on microglia phenotype switching and the subsequent brain injury and sought to elucidate the underlying mechanism. We conducted an endovascular perforation SAH model in mice. It was found that sestrin2 was significantly increased after SAH and was mainly distributed in neurons and microglia. Exogenous recombinant human sestrin2 (rh-sestrin2) evidently alleviated inflammatory insults and oxidative stress, and improved neurofunction after SAH. Moreover, rh-sestrin2 increased M2-like microglia polarization and suppressed the number of M1-like microglia after SAH. The protection by rh-sestrin2 was correlated with the activation of Nrf2 signaling. Nrf2 inhibition by ML385 abated the cerebroprotective effects of rh-sestrin2 against SAH and further manifested M1 microglia polarization. In conclusion, promoting microglia polarization from the M1 to M2 phenotype and inducing Nrf2 signaling might be the major mechanism by which sestrin2 protects against SAH insults. Sestrin2 might be a new molecular target for treating SAH.
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Factor 2 Relacionado con NF-E2 , Sestrinas , Hemorragia Subaracnoidea , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , Microglía/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Hemorragia Subaracnoidea/metabolismo , Sestrinas/metabolismoRESUMEN
PURPOSE: Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial for treatments. This study attempted to explore the relationships and tumor origin. METHODS: CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of ß-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. RESULTS: A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. ß-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CONCLUSIONS: CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.
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Craneofaringioma , Neoplasias Hipofisarias , Humanos , Hipotálamo , Hipófisis , beta CateninaRESUMEN
Objective: Postoperative hypopituitarism associated with increased risks of premature mobility and mortality is often encountered in craniopharyngioma patients. The aim of our study is to construct nomograms related to injury types of the hypothalamus-pituitary axis (HPA) to predict hypopituitarism 1 year after surgery. Methods: Craniopharyngioma patients undergoing initial endoscopic endonasal surgery between December 2012 and March 2021 in our center were retrospectively reviewed, and injury types of the HPA were categorized according to intraoperative endoscopic observation. Included patients were randomly divided into a training group and a validation group. Nomograms were established based on the results of multivariate logistic analysis. The predictive performance of the nomograms was evaluated in the training and validation groups. Results: A total of 183 patients with craniopharyngioma were enrolled, and seven injury types of the HPA were summarized. Relative to intact HPA, exclusive hypothalamus injury significantly increased the risk of anterior (OR, 194.174; 95% CI, 21.311-1769.253; p < 0.001) and posterior pituitary dysfunction (OR, 31.393; 95% CI, 6.319-155.964; p < 0.001) 1 year after surgery, while exclusively sacrificing stalk infiltrated by tumors did not significantly increase the risk of anterior (OR, 5.633; 95% CI, 0.753-42.133; p = 0.092) and posterior pituitary dysfunction (OR, 1.580; 95% CI, 0.257-9.707; p = 0.621) 1 year after surgery. In the training group, the AUCs of nomograms predicting anterior and posterior pituitary dysfunction 1 year after surgery were 0.921 and 0.885, respectively, compared with 0.921 and 0.880 in the validation group. Conclusions: Intact hypothalamus structure is critical in maintaining pituitary function. Moreover, our preliminary study suggests that the pituitary stalk infiltrated by craniopharyngioma could be sacrificed to achieve radical resection, without substantially rendering significantly worse endocrinological efficiency 1 year after surgery. The user-friendly nomograms can be used to predict hypopituitarism 1 year after surgery.
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Objective: The surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the "parasuprasellar" area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area. Methods: Surgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area. Results: The EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone (OC, optic strut and ACP) removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series. Conclusions: The EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON.
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OBJECTIVE: When comparing endoscopic endonasal surgery (EES) and transcranial microsurgery (TCM) for adult and mixed-age population craniopharyngiomas, EES has become an alternative to TCM. To date, studies comparing EES and TCM for pediatric craniopharyngiomas are sparse. In this study, the authors aimed to compare postoperative complications and surgical outcomes between EES and TCM for pediatric craniopharyngiomas. METHODS: The data of pediatric patients with craniopharyngiomas who underwent surgery between February 2009 and June 2021 at a single center were retrospectively reviewed. All included cases were divided into EES and TCM groups according to the treatment modality received. The baseline characteristics of patients were compared between the groups, as well as surgical results, perioperative complications, and long-term outcomes. To control for confounding factors, propensity-adjusted analysis was performed. RESULTS: Overall, 51 pediatric craniopharyngioma surgeries were identified in 49 patients, among which 35 were treated with EES and 16 were treated with TCM. The proportion of gross-total resection (GTR) was similar between the groups (94.3% for EES vs 75% for TCM, p = 0.130). TCM was associated with a lower rate of hypogonadism (33.3% vs 64.7%, p = 0.042) and a higher rate of growth hormone deficiency (73.3% vs 26.5%, p = 0.002), permanent diabetes insipidus (DI) (60.0% vs 29.4%, p = 0.043), and panhypopituitarism (80.0% vs 47.1%, p = 0.032) at the last follow-up. CSF leakage only occurred in the EES group, with no significant difference observed between the groups (p > 0.99). TCM significantly increased the risk of worsened visual outcomes (25.0% vs 0.0%, p = 0.012). However, TCM was associated with a significantly longer median duration of follow-up (66.0 vs 40.5 months, p = 0.007) and a significantly lower rate of preoperative hypogonadism (18.8% vs 60.0%, p = 0.006). The propensity-adjusted analysis revealed no difference in the rate of recurrence, hypogonadism, or permanent DI. Additionally, EES was associated with a lower median gain in BMI (1.5 kg/m2 vs 7.5 kg/m2, p = 0.046) and better hypothalamic function (58.3% vs 8.3%, p = 0.027) at the last follow-up. CONCLUSIONS: Compared with TCM, EES was associated with a superior visual outcome, better endocrinological and hypothalamic function, and less BMI gain, but comparable rates of GTR, recurrence, and perioperative complications. These findings have indicated that EES is a safe and effective surgical modality and can be a viable alternative to TCM for pediatric midline craniopharyngiomas.
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PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.
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Craneofaringioma , Águilas , Neoplasias Hipofisarias , Animales , Craneofaringioma/diagnóstico por imagen , Craneofaringioma/patología , Craneofaringioma/cirugía , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Hipotálamo/cirugía , Imagen por Resonancia Magnética/métodos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Estudios RetrospectivosRESUMEN
The site-selective C-H bond functionalization of heteroarenes can eventually provide chemists with great techniques for editing and building complex molecular scaffolds. During the past decade, benzo-fused N-heterocycles such as indoles and quinolines have been among the most widely investigated organic templates. Early developments have led to site-selective C-H bond functionalization on the pyrrole and pyridine cores of indoles and quinolines; however, C-H functionalization on the benzenoid ring has remained a great challenge in catalysis. In this review, we elaborate on recent developments in the highly challenging functionalization of C-H bonds on the less-reactive benzenoid core of indoles and quinolines. These findings are mainly described as selective directing group assisted strategies, remote C-H functionalization techniques and their reaction mechanisms. The underlying principle in each strategy is elucidated, which aims to facilitate the design of a more advanced structure of heterocycles based on bioactive molecules, synthetic drugs, and material aspects. Moreover, the challenges and perspectives for catalytic C-H functionalization to access the arene backbone of indoles and quinolines are also proposed in the conclusion section.
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Indoles , Quinolinas , CatálisisRESUMEN
OBJECTIVE: Suprasellar pituitary adenomas (PAs) can be located in either extradural or intradural spaces, which impacts surgical strategies and outcomes. This study determined how to distinguish these two different types of PAs and analyzed their corresponding surgical strategies and outcomes. METHODS: We retrospectively analyzed 389 patients who underwent surgery for PAs with suprasellar extension between 2016 to 2020 at our center. PAs were classified into two main grades according to tumor topography and their relationships to the diaphragm sellae (DS) and DS-attached residual pituitary gland (PG). Grade 1 tumors were located extradurally and further divided into grades 1a and 1b, while grade 2 tumors were located intradurally. RESULTS: Of 389 PAs, 292 (75.1%) were surrounded by a bilayer structure formed by the DS and the residual PG and classified as grade 1a, 63 (16.2%) had lobulated or daughter tumors resulting from the thinning or absence of the residual PG and subsequently rendering the bilayer weaker were classified as Grade 1b, and the remaining 34 (8.7%) PAs that broke through the DS or traversed the diaphragmic opening and encased suprasellar neurovascular structures were classified as Grade 2. We found that the gross total removal of the suprasellar part of grade 1a, 1b, and 2 PAs decreased with grading (88.4%, 71.4%, and 61.8%, respectively). The rate of major operative complications, including cerebrospinal fluid leakage, hemorrhage, and death, increased with grading. CONCLUSIONS: It is essential to identify whether PAs with suprasellar extension are located extradurally or intradurally, which depends on whether the bilayer structure is intact. PAs with an intact bilayer structure were classified as grade 1. These were extradural and usually had good surgical outcomes and lower complications. PAs with no bilayer structure surrounding them were classified as grade 2. These were intradural, connected to the cranial cavity, and had increased surgical complications and a lower rate of gross total removal. Different surgical strategies should be adopted for extradural and intradural PAs.
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BACKGROUND: It is well known that the clivus is composed of abundant cancellous bone and is often invaded by pituitary adenoma (PA), but the range of these cancellous bone corridors is unknown. In addition, we found that PA with clivus invasion is sometimes accompanied by petrous apex invasion, so we speculated that the petrous apex tumor originated from the clivus cancellous bone corridor. The aim of this study was to test this hypothesis by investigating the bony anatomy associated with PA with clival invasion and its clinical significance. METHODS: Twenty-two cadaveric heads were used in the anatomical study to research the bony architecture of the clivus and petrous apex, including six injected specimens for microsurgical dissection and sixteen cadavers for epoxy sheet plastination. The surgical videos and outcomes of PA with clival invasion in our single center were also retrospectively reviewed. RESULTS: The hypoglossal canal and internal acoustic meatus are composed of bone canals surrounded by cortical bone. The cancellous corridor within clivus starts from the sellar or sphenoid sinus floor and extends downward, bypassing the hypoglossal canal and finally reaching the occipital condyle and the medial edge of the jugular foramen. Interestingly, we found that the cancellous bone of the clivus was connected with that of the petrous apex through petroclival fissure extending to the medial margin of the internal acoustic meatus instead of a separating cortical bone between them as it should be. It is satisfactory that the anatomical outcomes of the cancellous corridor and the path of PA with clival invasion observed intraoperatively are completely consistent. In the retrospective cohort of 49 PA patients, the clival component was completely resected in 44 (89.8%), and only five (10.2%) patients in the early-stage had partial residual cases in the inferior clivus. CONCLUSION: The petrous apex invasion of PA is caused by the tumor invading the clivus and crossing the petroclival fissure along the cancellous bone corridor. PA invade the clivus along the cancellous bone corridor and can also cross the hypoglossal canal to the occipital condyle. This clival invasion pattern presented here deepens our understanding of the invasive characteristics of PA.
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Transition metal (TM)-catalysed directed hydroboration of aliphatic internal olefins which facilitates the construction of complex alkylboronates is an essential synthetic methodology. Here, an efficient method for the borylation of cyclopropanes involving TM-catalysed directed C-C activation has been developed. Upon exposure to neutral Rh(i)-catalyst systems, N-Piv-substituted cyclopropylamines (CPAs) undergo proximal-selective hydroboration with HBpin to provide valuable γ-amino boronates in one step which are otherwise difficult to synthesize by known methods. The enantioenriched substrates can deliver chiral products without erosion of the enantioselectivities. Versatile synthetic utility of the obtained γ-amino boronates is also demonstrated. Experimental and computational mechanistic studies showed the preferred pathway and the origin of this selectivity. This study will enable the further use of CPAs as valuable building blocks for the tunable generation of C-heteroatom or C-C bonds through selective C-C bond activation.
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[This corrects the article DOI: 10.1039/D0SC06186G.].
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Radical 1,1,2-trifunctionalization of terminal alkynes by an addition-translocation-cyclization-trapping sequence using readily available alkynyl triflones as trifluoromethyl radical precursors and trapping reagents is reported. Cascades occur by addition of the trifluoromethyl radical to a terminal alkyne, 1,5-hydrogen atom transfer, 5-exo-cyclization, and subsequent alkynylation to provide (1-trifluoromethyl)propargyl cyclopentanes. Reactions proceed with commercial dibenzoyl peroxide or α,α'-azobisisobutyronitrile as the initiator at elevated temperature and provide the highly substituted cyclopentanes in good yields.
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Different site selectivities have been reported for indoles with different directing groups in copper-catalyzed site-selective C-H arylations. Computational and mass spectrometric studies have been conducted in an effort to understand the origin of site selectivity and the effects of the directing groups. A Heck-like mechanism involving a four-membered ring is found in all three of the cases studied. For N-acetyl indole with a weak directing group, a neutral Heck-like mechanism is controlled by an electronic effect resulting in C2 site selectivity. In contrast, indole with a N-P(O) tBu2 group and N-benzyl-3-pivaloyl indole prefer a cationic Heck-like reaction in which a favorable six-membered chelation between the directing group and the CuIII center determines the C6 and C5 site selectivities.
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Recent advances in transition metal-catalyzed selective C-H functionalization of indoles have garnered tremendous attention. Great efforts have been devoted to C2 and C3 arylation because of the inherent reactivity of the pyrrole ring. Until recently, elegant methods have been developed to enable selective direct arylation on the benzenoid moiety at C4, C5, C6, and C7. This review highlights the contributions made in benzenoid direct arylation of indoles and presents their potential in organic synthesis.
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An effective and practical strategy has been established for the direct and site-selective arylation of indoles at the C4 and C5 positions with the aid of a readily accessible, cheap, and removable pivaloyl directing group at the C3 position. This transformation shows good functional-group tolerance and could serve as a powerful synthetic tool for the synthesis of medicinally relevant compounds. This method and those developed in previous research together enable the regiocontrolled direct arylation of indole at each C-H bond without prefunctionalization of the reactive sites.
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The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis. Furthermore, the level of malondialdehyde and the activity of superoxide dismutase (SOD) paired with glutathione peroxidase (GPx) were restored in the NBP treatment group. NBP promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus markedly, increased the expressions of Nrf2-ARE pathway-related downstream factors, including hemeoxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and prevented the decline of antioxidant enzyme activities, including SOD and GPx. NBP enhanced the translocation of Nrf2 to the nucleus from the cytoplasm,verified by a western blot, immunofluorescence. Additionally, it upregulated the expression of the Nrf2 downstream factors such as HO-1 and NQO1 were also confirmed via a western blot and real-time quantitative polymerase chain reaction. In conclusion, NBP administration may increase the activities of antioxidant enzymes and attenuate brain injury in a TBI model, potentially via the mediation of the Nrf2-ARE pathway.
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Benzofuranos/uso terapéutico , Lesiones Traumáticas del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Factor 2 Relacionado con NF-E2/biosíntesis , Fármacos Neuroprotectores/uso terapéutico , Transducción de Señal/fisiología , Animales , Benzofuranos/farmacología , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/prevención & control , Masculino , Ratones , Ratones Endogámicos ICR , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Distribución Aleatoria , Transducción de Señal/efectos de los fármacosRESUMEN
Venous hypertension(VH) plays an important role in the pathogenesis of cerebral arteriovenous malformations (AVMs) and is closely associated with the HIF-1α/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2) significantly influences angiogenesis; however, the interplay between Nrf2 and VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs. Immunohistochemistry indicated that Nrf2 and VEGF were highly expressed in human brain AVM tissues. In vivo, we established a VH model in both wild-type (WT) and siRNA-mediated Nrf2 knockdown rats. VH significantly increased the expression of Nrf2 and VEGF. Loss of Nrf2 markedly inhibited the upregulation of VEGF, as determined by Western blot analysis and qRT-PCR. In vitro, primary brain microvascular endothelial cells (BMECs) were isolated from WT and Nrf2-/- mice, and a VEGF-Nrf2 positive feed-back loop was observed in BMECs. By trans well assay and angiogenesis assay, Nrf2 knockout significantly inhibited the migration and vascular tube formation of BMECs. These findings suggest that the interplay between Nrf2 and VEGF can contribute to VH-induced angiogenesis in brain AVMs pathogenesis.
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Hipertensión/metabolismo , Malformaciones Arteriovenosas Intracraneales/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Neovascularización Patológica/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Movimiento Celular , Células Cultivadas , Circulación Cerebrovascular , Células Endoteliales/fisiología , Hemo-Oxigenasa 1/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Malformaciones Arteriovenosas Intracraneales/etiología , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Sistema de Señalización de MAP Quinasas , Masculino , Ratones Endogámicos ICR , Microvasos/patología , Microvasos/fisiopatología , Ratas Sprague-DawleyRESUMEN
Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI.