Finite element study of sagittal fracture location on thoracolumbar fracture treatment.

Background: Posterior internal fixation is the main method used for the treatment of thoracolumbar fractures. Fractures often occur in the upper 1/3 of the vertebral body. However, they can also occur in the middle or lower 1/3 of the vertebral body. At present, there is no report discussing the potential effects of sagittal location on instrument biomechanics or surgical strategy. The object of this study was to investigate the effect of the sagittal location of the fracture region of the vertebral body on the biomechanics of the internal fixation system and surgical strategy. Methods: A finite element model of the T11-L3 thoracolumbar segment was established based on a healthy person's CT scan. Different sagittal fracture location finite element models were created by resection of the upper 1/3, middle 1/3, and lower 1/3 of the L1 vertebral body. Three surgical strategies were utilized in this study, namely, proximal 1 level and distal 1 level (P1-D1), proximal 2 level and distal 1 level (P2-D1), and proximal 1 level and distal 2 levels (P1-D2). Nine fixation finite element models were created by combining fracture location and fixation strategies. Range of motion, von Mises stress, and stress distribution were analyzed to evaluate the effects on the instrument biomechanics and the selection of surgical strategy. Results: In all three different fixation strategies, the maximum von Mises stress location on the screw did not change with the sagittal location of the fracture site; nevertheless, the maximum von Mises stress differed. The maximum rod stress was located at the fracture site, with its value and location changed slightly. In the same fixation strategy, a limited effect of sagittal location on the range of motion was observed. P2D1 resulted in a shorter range of motion and lower screw stress for all sagittal locations of the fracture compared with the other strategies; however, rod stress was similar between strategies. Conclusion: The sagittal location of a fracture may affect the intensity and distribution of stress on the fixation system but does not influence the selection of surgical strategy.

[Study on Influencing Factors of Artificial Hip Joint Test Quality Based on ISO/IEC 17025 and GLP].

OBJECTIVE: Taking artificial hip joint test as the object, integrating ISO/IEC 17025 and GLP, and establishing a new set of management requirements for test influence factors. METHODS: The requirements of ISO/IEC 17025 and GLP regulations for influencing factors were compared and analyzed, the similarities and differences were found, and the two were integrated to formulate new management requirements for each influencing factor. RESULTS: From the personnel, equipment, materials, methods, reports, filing and other factors, a set of management requirements in line with ISO/IEC 17025 and GLP was formulated, so that the laboratory can provide the objective, real and accurate test data for medical equipment manufacturers and regulatory authorities. CONCLUSIONS: It can improve the test quality of the laboratory and ensure the authenticity and reliability of the test data and conclusions.

Investigation of the Friction Properties of a New Artificial Imitation Cartilage Material: PHEMA/Glycerol Gel.

The absence of artificial articular cartilage could cause the failure of artificial joints due to excessive material wear. There has been limited research on alternative materials for articular cartilage in joint prostheses, with few reducing the friction coefficient of artificial cartilage prostheses to the range of the natural cartilage friction coefficient (0.001-0.03). This work aimed to obtain and characterize mechanically and tribologically a new gel for potential application in articular replacement. Therefore, poly(hydroxyethyl methacrylate) (PHEMA)/glycerol synthetic gel was developed as a new type of artificial joint cartilage with a low friction coefficient, especially in calf serum. This glycerol material was developed via mixing HEMA and glycerin at a mass ratio of 1:1. The mechanical properties were studied, and it was found that the hardness of the synthetic gel was close to that of natural cartilage. The tribological performance of the synthetic gel was investigated using a reciprocating ball-on-plate rig. The ball samples were made of a cobalt-chromium-molybdenum (Co-Cr-Mo) alloy, and the plates were synthetic glycerol gel and two additional materials for comparison, which were ultra-high molecular polyethylene (UHMWPE) and 316L stainless steel. It was found that synthetic gel exhibited the lowest friction coefficient in both calf serum (0.018) and deionized water (0.039) compared to the other two conventional materials for knee prostheses. The surface roughness of the gel was found to be 4-5 µm through morphological analysis of wear. This newly proposed material provided a possible solution as a type of cartilage composite coating with hardness and tribological performance close to the nature of use in wear couples with artificial joints.

Effects of Occupational Exposure to Waste Anesthetic Gas on Oxidative Stress and DNA Damage.

OBJECTIVE: The aim of the study was to investigate the potential effects of waste anesthetic gas (WAG) on oxidative stress, DNA damage, and vital organs. METHODS: A total of 150 members of the staff at a hospital were assigned to an exposure group or control group. The 68 operating room (OR) staff in the exposure group were exposed to WAG, and the 82 non-OR staff in the control group were not exposed to WAG. Air samples were collected in the OR, and the sevoflurane concentrations in the samples were determined. Superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) in plasma from the participants were determined to assess oxidative stress. Western blot analysis was used to detect γH2AX in peripheral blood to assess DNA damage. Hematopoietic parameters, liver function, kidney function, and changes in electrophysiology were assessed to identify the effects on the vital organs. RESULTS: The mean (±standard deviation) sevoflurane concentration in 172 air samples from 22 operating rooms was 1.11 ± 0.65 ppm. The superoxide dismutase activity and vital organ parameters (lymphocyte, hemoglobin, and total protein concentrations and heart rate) were significantly lower (P < 0.05) in the exposed group than the control group. The malondialdehyde, total bilirubin, and creatinine concentrations and QT and QTc intervals were significantly higher (P < 0.05) in the exposed group than the control group. There were no significant differences between the glutathione peroxidase activities and γH2AX concentrations for the exposed and control groups. CONCLUSIONS: Long-term occupational exposure to waste anesthetic gas may affect the antioxidant defense system and probably affects vital organ functions to some extent. No correlation between DNA damage and chronic exposure to WAG was observed.

Novel combined shield design for eye and face protection from COVID-19.

The World Health Organization emphasized the importance of goggles and face shields for protection of medical personnel at the outbreak of the COVID-19 pandemic. Unsurprisingly, almost all countries suffered from a critical supply shortage of goggles and face shields, as well as many other types of personal protective equipment (PPE), for a long period, owing to the lack of key medical material supplies and the inefficiency of existing fabrication methods arising from the need to avoid crowds during the outbreak of COVID-19. In this paper, we propose a novel combined shield design for eye and face protection that can be rapidly fabricated using three-dimensional printing technology. The designed prototype eye-face shield is accessible to the general public, offering more possibilities for yield improvement in PPE during emergent infectious disease events such as COVID-19.

Microbial Profile During Pericoronitis and Microbiota Shift After Treatment.

The microflora of the distal pocket is considered as the major cause of pericoronitis. How the oral microflora changes during pericoronitis and whether different types of impacted third molar harbor the same microflora are still unknown. Saliva, subgingival plaque, and gingival plaque of mandibular third molars (M3Ms) were collected from twelve patients with acute pericoronitis. They were given local irrigation or local irrigation + antibiotics according to symptoms. Samples were harvested at the first visit with pericoronitis, 1 week after treatment, and 6 weeks after treatment. 16S rRNA gene polymerase chain reaction products were generated and sequenced after DNA isolation. Comparison of three sampling sites showed that, the subgingival plaque of M3Ms had most remarkable changes in symptomatic period, including a significant increase in microbial richness, and a convergent trend in microbial composition. After treatment, the subgingival microbiome was altered and largely returned to the state in asymptomatic period. In summary, the distal subgingival microbiota of M3M was most likely to be associated with the pathogenesis of pericoronitis. The post-treatment microbiota shift of M3M proved the effectiveness of treatment. The inclination type of impacted M3Ms and treatment method would also make a difference to the pericoronal microbiota.

How to improve the safety of bicortical pedicle screw insertion in the thoracolumbar vertebrae: analysis base on three-dimensional CT reconstruction of patients in the prone position.

BACKGROUND: Through the comparison of three-dimensional CT reconstruction between the supine position and the prone position, the relative position of thoracolumbar great vessels and vertebral body was studied, and the shortest safe distance between them was measured to improve the safety of bicortical pedicle screw insertion and reduce the risk of vascular injury. METHODS: Forty adults were selected to participate the research. Three-dimensional reconstruction of thoracolumbar (T9-L3) CT was performed in the prone position and the supine position. The relative distance between the Aorta/Inferior Vena Cava (IVC) and vertebral body was obtained as AVD/VVD respectively. The relative angle of the Aorta/ IVC and the vertebral body was calculated as ∠AOY/∠VOY. Self-controlled experiments were carried out in the prone and the supine positions, and the data obtained were analyzed using SPSS 22.0 statistical software. RESULTS: The AVD of the prone position and the supine position was the shortest at T12 (3.18 ± 0.68 mm), but the difference was not statistically significant. The aorta of the T9-L3 segment was shifted from the anterolateral to the anteromedial. The ∠AOY of the other groups differed significantly between the prone and supine positions in all vertebrae except T12 and L1 (P < 0.05), and the aorta in the prone position was more anteromedial than that of supine position. With regard to VVD/∠VOY, there was no significant difference between the prone and supine positions (P ≥ 0.05), and the minimum VVD of L3 segment is greater than 5.4 mm. The IVC has no obvious mobility and is fixed in the range of 20 ° ~ 30 ° near the midline. CONCLUSION: When using bicortical anchoring of pedicle screws, it is safe to ensure that the protruding tips of the screw is less than 3 mm. Due to the mobility of the aorta in different postures and individual differences in anatomy, the prone position CT can help doctors to make better preoperative plans and decisions.

ZJ01, a Small Molecule Inhibitor of the Kelch-Like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Protein-Protein Interaction, Reduces Hyperoxic Acute Lung Injury in a Mouse Model.

BACKGROUND Hyperoxic acute lung injury (ALI) is a complication of ventilation in patients with respiratory failure. Nuclear factor erythroid-2-related factor 2 (Nrf2) has an important role in ALI. Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2. ZJ01 is a small molecule inhibitor of Keap1-Nrf2 protein-protein interaction (PPI) that can reduce Keap1-induced inhibition of Nrf2. This study aimed to investigate the effects of ZJ01 and the heme oxygenase-1 (HO-1) inhibitor, zinc protoporphyrin IX (ZnPP IX), in a mouse model of hyperoxic ALI. MATERIAL AND METHODS C57BL/6J mice included five study groups: the room air+vehicle-treated group; the room air+ZJ01 group; the hyperoxia+vehicle-treated group; the hyperoxia+ZJ01 group; and the hyperoxia+ZJ01+ZnPP IX group. ZJ01, ZnPP IX, or vehicle were given 1 h after the hyperoxia challenge. The lungs from the mice were harvested at 72 h following the hyperoxia challenge. RESULTS Hyperoxia exposure for 72 h increased the activity of myeloperoxidase, the lung water content, the levels of tumor necrosis factor-alpha (TNF-alpha), and matrix metalloprotease-9 (MMP-9) in the vehicle-treated mice. ZJ01 treatment reduced hyperoxia-induced inflammation and increased the activation of Nrf2 and HO-1 compared with the vehicle-treated mice. Histology of the lungs showed that ZJ01 treatment reduced the changes of hyperoxia-induced ALI. Pretreatment with ZnPP IX reversed the beneficial effect of ZJ01. CONCLUSIONS ZJ01, a Keap1-Nrf2 PPI inhibitor, reduced hyperoxic ALI in a mouse model through the Nrf2/HO-1 pathway.

Postoperative outcomes of adult patients with sagittal fractures of mandibular condyle: Quantitative evaluation and retrospective factor analysis.

PURPOSE: We attempted to adopt quantitative methods to precisely evaluate the surgical effect of sagittal fractures of mandibular condyle (SFMCs) and aimed to determine differences in postoperative results between different groups of patients. MATERIALS AND METHODS: Postoperative data of patients with SFMC were collected and quantitative evaluations of subjective, clinical and imaging results were performed. SPSS software was used to analyze the data, and certain factors (gender, age, unilateral or bilateral SFMCs, injury time) were analyzed by univariate analysis. RESULTS: Forty-four postoperative patients were included with an average follow-up of 15.7 months. Averages of resting pain, moving pain, and chewing pain were all <10. Averages of maximum mouth opening, protrusion, and ipsilateral excursive movement were 42.20, 4.80, and 5.98 mm, respectively. Moreover, 85.71% of condylar healing and remodeling was good, and average condylar absorption was 1.52 mm. Early-operated patients (injury time ≤2 weeks) exhibited greater ipsilateral excursive movement, higher condylar index, and lesser condylar absorption than late-operated patients (injury time >2 weeks). Patients with unilateral SFMC showed greater protrusive movement and higher condylar index than those with bilateral SFMCs. CONCLUSION: Most patients with SFMCs could obtain good subjective, clinical and imaging results by appropriate surgical treatment. Early surgery could improve postoperative outcomes.

Effects of a 3D-printed orthosis compared to a low-temperature thermoplastic plate orthosis on wrist flexor spasticity in chronic hemiparetic stroke patients: a randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effects of two kinds of wrist-hand orthosis on wrist flexor spasticity in chronic stroke patients. DESIGN: This is a randomized controlled trial. SETTING: The study was conducted in a rehabilitation center. PARTICIPANTS: A total of 40 chronic hemiparetic stroke patients with wrist flexor spasticity were involved in the study. INTERVENTIONS: Patients were randomly assigned to either an experimental group (conventional rehabilitation therapy + 3D-printed orthosis, 20 patients) or a control group (conventional rehabilitation therapy + low-temperature thermoplastic plate orthosis, 20 patients). The time of wearing orthosis was about 4-8 hours per day for six weeks. MAIN MEASURES: Primary outcome measure: Modified Ashworth Scale was assessed three times (at baseline, three weeks, and six weeks). Secondary outcome measures: passive range of motion, Fugl-Meyer Assessment score, visual analogue scale score, and the swelling score were assessed twice (at baseline and six weeks). The subjective feeling score was assessed at six weeks. RESULTS: No significant difference was found between the two groups in the change of Modified Ashworth Scale scores at three weeks (15% versus 25%, P = 0.496). At six weeks, the Modified Ashworth Scale scores (65% versus 30%, P = 0.02), passive range of wrist extension (P < 0.001), ulnar deviation (P = 0.028), Fugl-Meyer Assessment scores (P < 0.001), and swelling scores (P < 0.001) showed significant changes between the experimental group and the control group. No significant difference was found between the two groups in the change of visual analogue scale scores (P = 0.637) and the subjective feeling scores (P = 0.243). CONCLUSION: 3D-printed orthosis showed greater changes than low-temperature thermoplastic plate orthosis in reducing spasticity and swelling, improving motor function of the wrist and passive range of wrist extension for stroke patients.

Xanthones and Quinolones Derivatives Produced by the Deep-Sea-Derived Fungus Penicillium sp. SCSIO Ind16F01.

Chemical investigation of the fungus Penicillium sp. SCSIO Ind16F01 derived from deep-sea sediment sample afforded a new xanthone, 3,8-dihydroxy-2-methyl-9-oxoxanthene-4-carboxylic acid methyl ester (1) and a new chromone, coniochaetone J (2), together with three known xanthones, 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (3), 7,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (4), 1,6,8-trihydroxy-3-(hydroxymethyl)anthraquinone (5), three known chromones, coniochaetone B (6), citrinolactones B (7), epiremisporine B (8), and four reported rare class of N-methyl quinolone lactams: quinolactacins B (9), C1 (10), and C2 (11), and quinolonimide (12). The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. Those isolated compounds were evaluated for their antiviral (EV71 and H3N2) and cytotoxic activities.

Relationship of IL-17A and IL-17F genetic variations to cervical cancer risk: a meta-analysis.

AIM: We performed a meta-analysis to determine a more precise relationship of IL-17A and IL-17F polymorphisms with cervical cancer risk. MATERIALS & METHODS: PubMed, CNKI and Wan Fang databases were searched for studies on these associations using STATA version 10.0 software. RESULTS: Five studies were included. The AG and AA genotypes and A allele of IL-17A rs2275913 were correlated with an elevated risk of cervical cancer. The TT genotype and T allele of IL-17A rs3748067 and the CC genotype and C allele of IL-17F rs763780 carried a moderate risk of cervical cancer, when compared with the wild-type genotype. CONCLUSION: IL-17A and IL-17F polymorphisms therefore have the potential to act as predictive biomarkers for cervical cancer risk.

Intraosseous Venous Malformations of the Zygoma: Report of 4 Cases and Literature Review.

OBJECTIVES: As intraosseous venous malformations (IVMs) of the zygoma are very rare and clinical features are not typical, a correct preoperative diagnosis may be difficult to make. This study presents 4 cases of IVM of the zygoma and gives a review of their clinical manifestations, radiographic features, preoperative diagnosis, and differentials. METHODS: The report of 4 cases was performed with an average 6-year follow-up. Medical records including clinical, radiographic, and histopathological information were reviewed. RESULTS: All the patients were mid-aged women with a complaint of an enlarging mass over the midface. They all failed to receive a definite preoperative diagnosis, and the diagnoses of IVM in all patients were made via pathological evidence. Although they received different surgical treatments, all the follow-up results (2~12 years) were satisfactory. CONCLUSION: Intraosseous venous malformations of the zygoma are benign lesions caused by abnormal vessel morphogenesis. Patients usually present in their 40s with a tender or painless swelling of the zygoma. The key to the diagnosis is the typical sunburst pattern of radiating trabeculae with intact cortices on computed tomographic scans. Intraosseous venous malformations should be differentiated from other lesions, including intraosseous meningioma, fibrous dysplasia, osteochondroma, osteosarcoma, and ossifying fibroma.

Application of a Computer-Assisted Navigation System (CANS) in the Delayed Treatment of Zygomatic Fractures: A Randomized Controlled Trial.

PURPOSE: The delayed treatment of zygomatic complex (ZMC) fracture presents a difficult challenge to surgeons. The aim of this study was to compare the treatment effects of delayed surgery of ZMC fractures with and without a computer-assisted navigation system (CANS). MATERIALS AND METHODS: In this observer-blinded single-site randomized clinical trial, patients with unilateral ZMC fracture were included and randomized 1:1 to delayed treatment with or without CANS. The primary outcome measurement was the absolute bilateral differences of the ZMC eminence and width based on computed tomographic (CT) measurements 48 to 72 hours after surgery. RESULTS: One hundred three patients with unilateral ZMC fracture without immediate treatment were enrolled, and 78 were randomized to each group. Postoperative CT measurements showed that the bilateral difference in ZMC eminence was significantly less for the navigation group than for the control group (1.24 vs 2.22 mm; P < .001). The bilateral difference in ZMC width was not significantly different between the 2 groups (0.94 vs 1.36 mm; P = .061). The percentage of patients exhibiting a morphologically symmetrical face (bilateral differences ≤2 mm in ZMC eminence and width) was 71.8% (28 of 39) for the navigation group and 35.9% (14 of 39) for the control group (P = .001). Photogrammetry showed that the average difference between the postoperative CT data and the preoperative design was smaller in the navigation group (1.30 vs 2.40 mm; P = .012). CONCLUSIONS: Use of CANS improved ZMC symmetry in patients with unilateral ZMC fracture who had delayed treatment by allowing for more accurate implementation of the preoperative plan.

Applied anatomy of the calcaneocuboid articular surface for internal fixation of calcaneal fractures.

BACKGROUND: Many types of steel plates are used for internal fixation of calcaneal fractures through extensive lateral approach. The fixation screw at the anterior calcaneal process must be placed into the dense compression trabeculae located directly under the calcaneocuboid articular surface to achieve a stable fixation. METHODS: The transverse diameter and inner tilt angle of the calcaneocuboid articular surface were measured and the inner structures near the calcaneocuboid articular surface were observed in forty adult calcaneus bone specimens to provide an anatomical basis for internal fixation of calcaneal fractures. RESULTS: The transverse diameter was 22.67 ± 2.14 mm and the inner tilt angle was 60.4 ± 7.1°. CONCLUSION: Screws should be implanted under the calcaneocuboid articular surface and the length and direction of the screw should be selected according to the transverse diameter of the calcaneal articular surface and the inner tilt angle, respectively.

[Discussion on developing a data management plan and its key factors in clinical study based on electronic data capture system].

Data management has significant impact on the quality control of clinical studies. Every clinical study should have a data management plan to provide overall work instructions and ensure that all of these tasks are completed according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the data management plan (DMP) is an auditable document requested by regulatory inspectors and must be written in a manner that is realistic and of high quality. The significance of DMP, the minimum standards and the best practices provided by GCDMP, the main contents of DMP based on electronic data capture (EDC) and some key factors of DMP influencing the quality of clinical study were elaborated in this paper. Specifically, DMP generally consists of 15 parts, namely, the approval page, the protocol summary, role and training, timelines, database design, creation, maintenance and security, data entry, data validation, quality control and quality assurance, the management of external data, serious adverse event data reconciliation, coding, database lock, data management reports, the communication plan and the abbreviated terms. Among them, the following three parts are regarded as the key factors: designing a standardized database of the clinical study, entering data in time and cleansing data efficiently. In the last part of this article, the authors also analyzed the problems in clinical research of traditional Chinese medicine using the EDC system and put forward some suggestions for improvement.

[A multicenter prospective randomized open comparative study on the treatment of ovulatory menorrhagia with tranexamic acid and norethisterone in China].

OBJECTIVE: To compare the efficacy and safety of tranexamic acid (TA) and norethisterone (NET) for the treatment of patients with ovulatory menorrhagia in China. METHODS: One hundred and thirty one patients with proven ovulatory menorrhagia from gynecologic clinics of 5 teaching hospitals located in 4 different cities in China were enrolled during Jul 2004 to Dec 2006. Among them 128 completed the study. Patients were randomly divided into two therapeutic regimen groups: TA 1 g thrice daily during menstrual cycle days (D) 1-5, 69 cases; or NET 5 mg twice daily on D19-26, 59 cases. The drugs were administered for 2 consecutive cycles, then withdrawn and patients were followed-up for 1 more cycle. Data on menstrual blood loss [estimated by pictorial blood assessment chart (PBAC)], length of menstrual periods, quality of life (QOL) evaluated by a 6 item health-related questionnaire were collected before, during each cycle and were compared. RESULTS: Both treatments led to significant decreases of mean PBAC scores and shorter duration of menstrual periods, and improved the QOL ranking during the two treatment cycles. The mean percentages of PBAC decrements in the TA first and second cycles were significantly greater than those in the NET corresponding cycles(35% vs 17% , P = 0.004; 44% vs 34%, P = 0.04 respectively). The success rate of TA second cycle was higher than that of the NET second cycle (41% vs 24%, P = 0.04). Improvement of QOL ranking in the TA first cycle was also significantly better than those in the NET first cycle (P = 0.03). The percentage of patients with at least 1 adverse event in TA group (19%) was significantly lower than that in NET group (35%, P = 0.04). Patients' willingness to continue the treatment in the TA second and follow-up cycles (94%, 79% respectively) were significantly higher than those in the corresponding cycles of NET groups (79%, 59% respectively; P = 0.01, P = 0.02). CONCLUSION: The regimen of TA 3 g daily during menstrual days 1-5 is a more effective and tolerable treatment than luteal phase norethisterone for patients with ovulatory menorrhagia.

[The status quo of perimenopausal and postmenopausal women in Chengdu: report of a population-based cross-sectional study].

OBJECTIVE: To investigate the situation of reproductive health of perimenopausal and postmenopausal women in Chengdu and provide a basis for planning reproductive health care for these women. METHODS: We conducted a population-based cross-sectional study in women who were over 45 years old in the central city and the nearby county of Chengdu. RESULTS: The mean age of menopause was 48.1 years. There were sixty percent of women who had dysfunctional uterine bleeding before menopause. About half of the postmenopausal women had experienced perimenopausal symptoms. There were 460 women who ever used or currently use estrogen therapy. But only half of them visited doctors and sought medical therapy. And the main problems were hot flash, night sweats, dyssomnia, and urinary infection. Most of them took medicine for a short period (< 1 year). CONCLUSION: We found that middle-aged and older women have many symptoms related to menopause. It is necessary for us to provide reproductive health care for them.

Multiple caspases are activated after traumatic brain injury: evidence for involvement in functional outcome.

Caspase-3 is a cysteine protease that is strongly implicated in neuronal apoptosis. Activation of caspase-3 may be induced by at least two major initiator pathways: a caspase-8-mediated pathway activated through cell surface death receptors (extrinsic pathway), and a caspase-9-mediated pathway activated by signals from the mitochondria that lead to formation of an apoptosomal complex (intrinsic pathway). In the present studies, we compare the activation of caspases-3, -8, and -9 after lateral fluid-percussion traumatic brain injury (TBI) in rats. Immunoblot analysis identified cleaved forms of caspases-3 and -9, but not caspase-8, at 1, 12, and 48 h after injury. Immunocytochemistry specific for cleaved caspases-3 and -9 revealed their expression primarily in neurons. These caspases were also frequently localized in TUNEL-positive cells, some of which demonstrated morphological features of apoptosis. However, caspases-3 and -9 were also found in neurons that were not TUNEL-positive, and other TUNEL-positive cells did not show activated caspases. In contrast to caspases-3 or -9, caspase-8 expression was only minimally changed by injury. An increase in expression of this caspase was undetectable by immunoblotting methods, and appeared as positive immunostaining restricted to a few cells within the injured cortex. Treatment with the pan-caspase inhibitor z-VAD-fmk at 15 min after TBI improved performance on motor and spatial learning tests. These data suggest that several caspases may be involved in the pathophysiology of TBI and that pan-caspase inhibition strategies may improve neurological outcomes.