Number of intra-operative cyclic knee motion required to achieve stable graft tension in anterior cruciate ligament reconstruction; a prospective clinical study.

BACKGROUND: Applying pretension by cyclic knee motion immediately before graft fixation in anterior cruciate ligament (ACL) reconstruction surgery decreases graft elongation during the postoperative course. However, the expected change in graft tension caused by cyclic knee motion remains unclear. We measured graft tension changes caused by cyclic knee motion during double-bundle ACL reconstruction. METHODS: We included 39 patients undergoing primary anatomical double-bundle ACL reconstruction with autologous hamstrings as graft sources, at multiple centers between February 2021 and August 2022. After securing the anteromedial (AM) and posterolateral (PL) bundle grafts to the femoral cortex, they were initially tensioned to 40 N per bundle. After 10 cycles of knee extension and flexion motion, ranging from 0 to 90-110°, tension was re-measured and re-tensioned to 40 N if the graft tension had decreased. This was repeated thrice for 10 cycles on each graft. Every 10 cycles, we recorded graft tension changes (ΔGT) and compared the mean ΔGT in the AM and PL bundles. Furthermore, we assessed relationships between total ΔGT in each bundle, age, sex, and graft diameter. RESULTS: Twenty-five women and 14 men with a mean age of 27.4 ± 12.4 years were included. The mean ΔGT in AM and PL bundles after every 10 cycles were 6.6 ± 3.7 N, 3.0 ± 2.3 N, 1.4 ± 1.5 N, and 9.9 ± 3.8 N, 4.9 ± 2.6 N, and 2.5 ± 1.9 N, respectively. There were significant differences in ΔGT in both bundles after every 10 cycles (p < 0.01). ΔGT in the AM bundle was significantly lower than in the PM bundle at the same number of cycles (p < 0.01). No correlation was observed between ΔGT in either bundle and age, sex, or graft diameter. CONCLUSIONS: The initially applied graft tension decreased by intra-operative cyclic knee movement, and the changes in graft tension decreased after retention and repeated cycles. Three sets of 10 cycles knee motion may avoid initial tension loss of the hamstring autograft in the early phase after double-bundle ACL reconstruction.

Lateral meniscal injury without medial meniscal injury indicates the existence of the Segond fracture in ACL-deficient knees.

Background/Objective: The purpose of this study was to find factors indicating the occurrence of the Segond fracture, a specific type of anterolateral ligament injury. Methods: From January 2015 to December 2017, we retrospectively reviewed the medical records of patients diagnosed with acute anterior cruciate ligament (ACL) injury who underwent reconstruction within 90 days of injury. Diagnosis of the Segond fracture was determined either by magnetic resonance imaging or plain radiographs. Factors examined were: age at surgery, sex, body mass index (kg/m2), status of menisci, and activities led to ACL injury. After univariate screening, multivariate logistic regression analyses were performed. Patients were divided into four groups based on the presence of lateral meniscal (LM) and/or medial meniscal (MM) injuries and compared with respect to the occurrence of Segond fractures. Results: A total of 375 patients were included (163 males, 212 females), with mean age 25.8 years old. Among them, 22 of 375 (5.9 %) had a Segond fracture. We identified injured lateral menisci (adjusted odds ratio (aOR), 3.029; 95 % Confidence Interval (CI), 1.206-7.609; P = 0.018), intact medial menisci (aOR, 0.229; 95 % CI, 0.065-0.810; P = 0.022), and higher body mass index (aOR, 1.102; 95 % CI, 1.008-1.205; P = 0.034) as factors indicative of the occurrence of Segond fracture. LM injury without MM injury suggested the existence of a Segond fracture. Conclusion: LM injury without a MM injury indicated the occurrence of a Segond fracture. Higher body mass index also increased the risk for Segond fracture occurrence.

Exocrine Pancreatic Insufficiency Possibly Related to Atypical Chronic Graft-versus-Host Disease.

We report the case of a 66-year-old woman who presented with diarrhea and weight loss approximately 14 months after unrelated allogeneic bone marrow transplantation for acute myeloid leukemia. Her early post-transplant course was notable for mild acute skin graft-versus-host disease (GVHD) and biopsy-proven upper gastrointestinal (GI) acute GVHD, both of which resolved with treatment. She then developed weight loss and diarrhea treated with prednisolone for what was thought to be GI late acute GVHD. However, her diarrhea and weight loss persisted. Colonoscopy showed a grossly intact mucosa, and stool studies only confirmed steatorrhea. However, an atrophic pancreas was found on an abdominal computed tomography (CT) scan. Exocrine pancreatic enzymes, such as lipase and pancreatic amylase, were markedly decreased, yet pancreatic endocrine function remained intact. The patient's diarrhea and weight loss improved upon treatment with pancrelipase. Therefore, we suggest that her exocrine pancreatic insufficiency was likely partly caused by atypical chronic GVHD.

Validity of the Center-Center Method for the Syndesmotic Fixation Axis Compared to the Transsyndesmotic Axis.

BACKGROUND: Placement of clamp forceps along the transsyndesmotic (TS) axis reduces the risk of iatrogenic syndesmotic malreduction during ankle fracture surgery with tibiofibular diastasis. This study aimed to measure the difference between the TS axis and the axis determined by an intraoperative fluoroscopic technique using the center-center (CC) method. We also compared the values obtained when the CC method was performed at different heights from the tibial plafond. METHODS: We evaluated the computed tomography scans of 150 patients with normal syndesmosis. The CC method was simulated using digitally reconstructed radiographs. The TS and CC axes were projected onto an axial computed tomographic image linked to digitally reconstructed radiography. The angle between the two axes (interaxis angle) and the distance between the intersection of these axes and the medial tibial cortex (interaxis distance) were measured. The procedures were performed 0, 10, and 20 mm proximal to the tibial plafond, and the measurements were compared among the different heights using a 1-way repeated-measures analysis of variance. RESULTS: The TS axis was found to be externally rotated to the CC axis, with an interaxis angle of 8.5 degrees (SD, 6.8 degrees). The interaxis angle increased from 1.9 degrees at a height of 0 mm to a greater angle at higher heights (P < .001). The overall interaxis distance was 7.7 (SD, 6.3) mm, increasing from 2.0 mm at a height of 0 mm to a greater distance at higher heights (P < .001). CONCLUSION: The TS axis was externally rotated relative to the CC axis, and the difference between the 2 axes was greater when the CC method was performed on the higher heights from the tibial plafond. To clamp the syndesmosis along the TS axis, the CC method should be applied close to the ankle joint. LEVEL OF EVIDENCE: Level IV, case series.

The influence of COVID-19 pandemic on the incidence of knee pain and physical activity level in children and adolescents in Japan: A prospective observation study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on children's lifestyles. Some studies have reported psychological changes in children after the pandemic, but information on musculoskeletal problems is scarce. This study aimed to investigate the incidence of knee pain and changes in physical activity after the spread of COVID-19 among elementary and junior high school students in Japan. METHODS: Knee pain and amount of physical activity were recorded on a monthly basis between August 2019 and February 2021 in children aged 8-14 years using a self-administered questionnaire. The amount of physical activity was scored using the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS). The period until February 2020 was defined as "Before pandemic," and the period from March 2020 was defined as "After pandemic." The incidences of knee pain and HSS Pedi-FABS scores before and after the COVID-19 pandemic were compared. Additionally, we compared the prevalence of knee pain and HSS Pedi-FABS scores according to sex and age. RESULTS: We enrolled 886 and 881 participants before and after the pandemic, respectively. The prevalence of knee pain among the participants before and after the pandemic was 6.7% and 7.9%, respectively (p = 0.032). The mean HSS Pedi-FABS scores before and after the pandemic were 14.8 and 14.5, respectively (p = 0.005). Participants aged 14 years had a significantly lower incidence of knee pain (p = 0.013) and significantly higher HSS Pedi-FABS scores (p < 0.001) after the spread of COVID-19. CONCLUSIONS: In elementary and junior high school students, increase in the incidence of knee pain and decrease in the amount of physical activity after the spread of COVID-19 were observed.

Nuclear receptor subfamily 1 group D member 1 in the pathology of obesity-induced osteoarthritis progression.

Mechanical overload and chemical factors are both related to obesity-induced progression of knee osteoarthritis. The circadian rhythm is related to the development of metabolic syndrome and the progression of osteoarthritis, and the core clock genes nuclear receptor subfamily 1 group D member 1 (NR1D1) and brain and muscle arnt-like protein 1 (BMAL1) are dysregulated in cartilage from patients with osteoarthritis. Here, we focused on NR1D1 and investigated osteoarthritis-related changes and gene expression in a mouse model of diet-induced obesity. A high-fat diet was provided to C57BL6/J mice, and changes in body weight, blood lipids, and gene expression were investigated. Destabilization of the medial meniscus or sham surgery was performed on mice fed a high-fat diet or normal diet, and histological osteoarthritis-related changes and NR1D1 expression were investigated. The effects of the NR1D1 agonist SR9009 were also assessed. Mice fed a high-fat diet developed significant obesity and dyslipidemia. Nr1d1 and Bmal1 gene expression levels decreased in the liver and knee joints. Moreover, increased osteoarthritis progression and decreased NR1D1 protein expression were observed in high-fat diet-fed mice after surgical osteoarthritis induction. SR9009 decreased the progression of obesity, dyslipidemia, and osteoarthritis. Overall, obesity and dyslipidemia induced by the high-fat diet led to osteoarthritis progression and decreased NR1D1 expression. Thus, NR1D1 may play an important role in obesity-induced osteoarthritis.

Risk factors for the occurrence and protraction of patellar and patellar tendon pain in children and adolescents: a prospective cohort study of 3 years.

BACKGROUND: Patellar and patellar tendon pain is a common limitation to children's participation in social and physical activities. Some factors have been implicated in the occurrence and protraction of knee pain, but the causal relationship is unknown. The purpose of this study was to investigate whether participants' physical characteristics and activity level are risk factors for the occurrence and protraction of patellar and patellar tendon pain in children and adolescents. METHODS: A three-year prospective cohort study was conducted with healthy students who were aged 8-14 years old, in Japan. Height, weight, heel-buttock distance, straight leg raising angle, and dorsiflexion angle of the ankle joint were collected as individual physical factors at the beginning of each year. The presence of self-reported patellar and patellar tendon pain and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) was collected every month. Protraction was defined as either (1) pain lasting for more than three continuous months or (2) recurrent pain after more than three months of complete recovery. Participants who did not have any pain at the beginning of the observation period were included in the analysis. We analyzed the odds ratio (OR) of pain occurrence within a year of registration and protraction throughout the study period for all physical factors and HSS Pedi-FABS. RESULTS: We included 1133 participants in the analysis and 252 participants developed knee pain within a year. 34.8% of participants with pain experienced protraction during the follow-up period. A high HSS Pedi-FABS significantly predicted knee pain occurrence (OR 1.03, 95% confidence interval [CI] 1.01-1.05) and protraction (OR 1.03, 95% CI 1.00-1.05). In addition, younger children and girls were at a significantly higher risk of patellar and patellar tendon pain protraction (age, OR 0.81, 95% CI, 0.73-0.90; sex, OR 1.69, 95% CI, 1.09-2.64). Other physical factors did not significantly predict the occurrence or protraction of knee pain. CONCLUSIONS: This study showed that a greater physical activity level was a risk factor for the occurrence and protraction of patellar and patellar tendon pain in childhood. In addition, younger age and female sex predicted higher risk of protraction of pain.

Comparison of joint awareness after medial unicompartmental knee arthroplasty and high tibial osteotomy: a retrospective multicenter study.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are established treatments for medial compartment osteoarthritis (OA) or osteonecrosis (ON) of the knee joint, and the predominance of either procedure is inconclusive. We compared the awareness of the knee after UKA and HTO using the Forgotten joint score-12 (FJS). MATERIALS AND METHODS: This was a retrospective, multicenter study. Ninety-six knees of 90 patients who received UKA or HTO and were followed-up for at least 1 year were analyzed. Postoperative FJS was compared between the two groups and evaluated for the effect of patient-related factors and clinical outcomes. Multiple linear regression analysis was performed to predict FJS. RESULTS: There was no significant difference in the FJS between the UKA and HTO groups (p = 0.24). FJS did not correlate with any of the patient-related factors. There was a correlation between the FJS and each item of the Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Lysholm Knee Scoring Scale (LKS). In multiple linear regression analysis, lower BMI, the diagnosis of OA Kellgren-Lawrence (KL) grade ≥ 3, and ON were significant predictors of better FJS. In both groups, FJS was correlated with each item of the KOOS and LKS. Internal consistency in terms of Cronbach's alpha was excellent. CONCLUSIONS: There was no significant difference in FJS between patients who underwent UKA and HTO. Lower BMI, the diagnosis of OA KL grade ≥ 3, and ON were significant predictors of better FJS.

Effect of Systemic Administration of Granulocyte Colony-Stimulating Factor on a Chronic Partial-Thickness Cartilage Defect in a Rabbit Knee Joint.

OBJECTIVE: Cartilage lesions in the knee joint can lead to joint mechanics changes and cause knee pain. Bone marrow stimulation (BMS) promotes cartilage regeneration by perforating the subchondral bone just below the injury and inducing bone marrow cells. This study aimed to investigate whether systemic administration of granulocyte colony-stimulating factor (G-CSF) with BMS improves repair of chronic partial-thickness cartilage defects (PTCDs). DESIGN: Eighteen 6-month-old New Zealand white rabbits were divided into 3 groups: control (C, n = 6), BMS alone (n = 6), and BMS + G-CSF (n = 6). Partial cartilage defects with 5 mm diameter were created in the trochlear region of both knees; after 4 weeks, the BMS alone and BMS + G-CSF groups underwent BMS; G-CSF (50 µg/kg) or saline was administered subcutaneously for 5 days starting from 3 days before BMS. At 8 and 16 weeks after cartilage defect creation, the area of cartilage defects was macroscopically and histologically evaluated. RESULTS: International Cartilage Repair Society (ICRS) grades for macroscopic assessment were 0, 0.7, and 0.7 at 8 weeks and 0, 1.2, and 1.3 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. Wakitani scores for histological assessment were 9.8, 8.7, and 8.2 at 8 weeks and 9.5, 9, and 8.2 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. The BMS + G-CSF group showed significantly more repair than the C group, but there was no difference from the BMS group. CONCLUSIONS: The effect of BMS and G-CSF on chronic PTCDs in mature rabbit knees was limited.

Changes in the Syndesmotic Reduction After Syndesmotic Suture-Button Fixation for Ankle Malleolar Fractures: 1-Year Longitudinal Evaluations Using Computed Tomography.

BACKGROUND: Evaluation over time is important in assessing the reduction of the syndesmosis after suture-button fixation for ankle malleolar fractures. The purposes of this study were to evaluate time-dependent change in the syndesmotic reduction immediately after suture-button fixation for ankle malleolus fractures and 1 year after surgery using computed tomography, and to investigate the reliability of the measurement values to evaluate the reduction of syndesmosis. METHODS: We assessed 28 patients who underwent suture-button fixation for ankle fractures. Syndesmotic reduction was assessed within 2 weeks of the fracture surgery and 1 year after surgery using axial computer tomographic images. Side-to-side differences in the anterior, central, and posterior tibiofibular distances, anteroposterior fibular translation, fibular rotation, and syndesmosis area were measured. RESULTS: The mean anterior tibiofibular distance and anteroposterior fibular translation were 1.8 mm and 1.5 mm, respectively, after syndesmotic fixation. They decreased to 1.2 mm and 0.6 mm, respectively, at 1 year after surgery (P = .03 and P = .01, respectively). The other measurement values did not change over time. The minimum detectable change in the distance of measurements was 1 mm or less. CONCLUSION: The anterior tibiofibular distance and anteroposterior fibular translation had decreased 1 year after fixation in ankle malleolar fractures with syndesmotic suture button. Even if the fibula is posteriorly malreduced by the time computed tomography is performed immediately after surgery, the fibula may return to a good position 1 year after surgery. LEVEL OF EVIDENCE: Level IV, case series.

Intra- and inter-observer reliability of implant positioning evaluation on a CT-based three-dimensional postoperative matching system for total knee arthroplasty.

BACKGROUND: The evaluation of postoperative total knee arthroplasty (TKA) alignment mainly relies on measurement data obtained from plain radiographs. The aim of this retrospective observational study was to document the intra- and inter-observer reliability in assessment of TKA component positioning after surgery using a three-dimensional (3D) computed tomography (CT) image matching system. METHODS: Fourteen knees from 14 patients who received primary TKA were included, and images were analyzed by blinded readers not associated with the surgeries. The examiner digitized the reference points according to defined landmarks, and the designated size component was superimposed to the 3D reconstructed CT model for measurement. In addition to the evaluation of implant position against the coronal and sagittal lower limb mechanical axes that were defined based on bony landmarks, implant position against axes connecting implant-based reference points that are easier to indicate was evaluated. RESULTS: The overall intra- and inter-observer reliabilities determined by the intraclass correlation coefficients (ICC) of the implant alignment measurement for both femoral and tibial components were good (ICC > 0.60), except in the direction of femoral flexion and extension, for both mechanical and implant-based axes. The difference between implant alignment measurements according to the traditional mechanical axis and the implant-based axis ranged between means of 0.08o and 1.70o and were statistically significantly different. CONCLUSIONS: The postoperative evaluation of implant position in the coronal and sagittal planes using 3D-CT image matching is reliable and has good reproducibility except for the sagittal alignment assessment of the femoral component. The measured implant position according to the traditional mechanical axis and the implant-based axis were slightly but significantly different.

In vivo kinematics of cruciate-retaining total knee arthroplasty after a change of polyethylene insert configuration.

BACKGROUND: To investigate in vivo kinematics of total knee arthroplasty (TKA) with the introduction of a mildly constrained (MC) type of polyethylene (PE). We compared the knee kinematics with a reported pattern after surgery using the same component with a conventionally constrained (CC) type of PE. METHODS: Finite element analysis (FEA) was performed to examine different peak stress distribution of both types of PE. For in vivo study, patients who underwent cruciate-retaining TKA using a total knee system with MC-PE were included. Fluoroscopic surveillance was used to measure the weight-bearing deep knee bend (squatting) using a two-dimensional/three-dimensional (2-D/3-D) registration technique. RESULTS: FEA analysis revealed the edge loading of the femoral component on PE in CC but not in MC. During the study period, 42 patients underwent TKA with MC-PE. Among them, 13 agreed to participate in the present study. In vivo kinematics analysis found that starting from an average external rotation of femur being 7.1° at 0° of flexion, the rotation slightly decreased to 6.8° at 10° of flexion, then increased with increasing knee flexion until it reached 10.8° at 80° of flexion, and finally decreased to 9.8° at 100° of knee flexion. The results indicate a modest medial pivot pattern. Although the overall pattern was similar for both MC-PE and CC-PE, a slight difference was observed. MC-PE showed a slight internal rotation of 0.3° from 0 to 10° of knee flexion, whereas CC-PE showed a gradual increase of external rotation in this range. CONCLUSIONS: Change of configuration from CC to MC did not substantially affect in vivo kinematics of knees after TKA. Considering the theoretical wider range of allowance of rotation, MC-PE is easier for knee surgeons to use.

The shape of the first metatarsal head and its association with the presence of sesamoid-metatarsal joint osteoarthritis and the pronation angle.

BACKGROUND: The purpose of this study was to evaluate the associations of the shape of the first metatarsal head with (1) the presence of osteoarthritis in the sesamoid-metatarsal joint and (2) the pronation angle of the first metatarsal head on foot radiographs. METHODS: A total of 121 patients, with the mean age of 61 years, underwent weight-bearing dorsoplantar, lateral, and first metatarsal axial radiographs. The shape of the first metatarsal head's lateral edge was classified as either rounded, intermediate, or angular in shape in the dorsoplantar view. The presence of osteoarthritis in the sesamoid-metatarsal joint and the pronation angle of the first metatarsal head were assessed in the first metatarsal axial view. Other variables that could affect the first metatarsal shape, including the lateral first metatarsal inclination angle, were also assessed. Univariate and multivariate analyses were performed to determine the associations. RESULTS: The prevalence of sesamoid-metatarsal osteoarthritis was significantly higher (77%, 27%, and 29% for rounded, intermediate, and angular, respectively, P < .001), and the metatarsal pronation angle was significantly larger (14°, 8°, and 4° for rounded, intermediate, and angular, respectively, P < .001) in feet with a rounded metatarsal head. These associations were also significant in the multiple regression analysis. CONCLUSION: A rounded metatarsal head was associated with a higher prevalence of osteoarthritis within the sesamoid-metatarsal joint, as well as a larger first metatarsal head pronation angle. A negative round sign can be used as a simple indicator of an effective correction to the first metatarsal pronation angle during hallux valgus surgery. However, in feet with sesamoid-metatarsal osteoarthritis, surgeons will need to be cautious as overcorrection may occur.

Long-term survival after cord blood transplantation for acute myeloid leukemia complicated with disseminated fusariosis.

Fusariosis is a critical infectious complication that can develop in immunocompromised hosts, mainly under conditions of prolonged neutropenia, and is often disseminated and associated with a high mortality rate. Disseminated fusariosis developing during the course of hematopoietic stem cell transplantation (HSCT) is a critical condition, and there have been few reports of successful treatment of cases complicated with fusariosis before HSCT. Here, we present a case of acute myeloid leukemia (AML) with the development of fungal endophthalmitis during chemotherapy. Vitrectomy was performed and Fusarium solani infection was confirmed by vitreal culture. The infection was also disseminated to the lung, triceps, and spleen. The splenic lesions disappeared with the administration of antifungal agents, and residual lesions in the lung and triceps were surgically resected. After two courses of consolidation chemotherapy, the patient received cord blood transplantation (CBT) twice because of graft failure in the first transplantation. Antifungal agents were administered continuously during chemotherapy and transplantation. Although Fusarium sinusitis developed after neutrophil engraftment, it was well controlled by surgical resection. Thereafter, the patient has been well without recurrence of fusariosis for more than 2 years since transplantation. A combination of continuous administration of antifungal agents and vigorous surgical intervention may be important for management of disseminated fusariosis in the setting of HSCT.

Successful Treatment of Aggressive Mature B-cell Lymphoma Mimicking Immune Thrombocytopenic Purpura.

A 55-year-old woman suffered from hemorrhagic tendency. She had severe thrombocytopenia without any hematological or coagulatory abnormalities, and a bone marrow examination revealed an increased number of megakaryocytes without any abnormal cells or blasts. No lymphadenopathy or hepatosplenomegaly was observed on computed tomography. She was initially diagnosed with immune thrombocytopenic purpura (ITP). None of the treatments administered for ITP produced a response. However, abnormal cells were eventually found during the third bone marrow examination. The pathological diagnosis was mature B-cell lymphoma. Rituximab-containing chemotherapy produced a marked increase in the patient's platelet count, and her lymphoma went into complete remission.

Remote Hemorrhage in the Cerebellum and Temporal Lobe after Lumbar Spine Surgery.

Cerebellar hemorrhage remote from the site of surgery can complicate neurosurgical procedures. However, this complication after lumbar surgery is rare. Furthermore, hemorrhage in both the cerebellum and the temporal lobe after spine surgery is rarer still. Herein we present a case of remote hemorrhage in both the cerebellum and the temporal lobe after lumbar spine surgery. A 79-year-old woman with a Schwannoma at the L4 level presented with low back and bilateral leg pain refractory to conservative management. Surgery was undertaken to remove the Schwannoma and to perform posterior fusion. During the surgery, the dura mater was removed in order to excise the Schwannoma. Reconstruction of the dura mater was performed; postoperatively the patient had a cerebrospinal fluid leak. Five days after surgery, clouding of consciousness started gradually, and hemorrhage in the cerebellum and the temporal lobe was revealed by computed tomography. Emergent evacuation of the hemorrhage was performed and the patient recovered consciousness after the surgery. Leakage of cerebrospinal fluid may have induced this hemorrhage. While rare, intracranial hemorrhage after spine surgery can occur, sometimes requiring emergent intervention.

Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats.

BACKGROUND: Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD. RESULTS: In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B. CONCLUSIONS: The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.