No abstract

Background Microglia play crucial roles in the maintenance of brain homeostasis. Activated microglia show a biphasic influence, promoting beneficial repair and causing harmful damage via M2 and M1 microglia, respectively. It is well-known that microglia are initially activated to the M2 state and subsequently switch to the M1 state, called M2-to-M1 class switching in acute ischemic models. However, the activation process of microglia in chronic and sporadic hypertension remains poorly understood. We aimed to clarify the process using a chronic hypertension model, the deoxycorticosterone acetate (DOCA)-salt-treated Wistar rats. Methods After unilateral nephrectomy, the rats were randomly divided into DOCA-salt, placebo, and control groups. DOCA-salt rats received a weekly subcutaneous injection of DOCA (40 mg/kg) and were continuously provided with 1% NaCl in drinking water. Placebo rats received a weekly subcutaneous injection of vehicle and were provided with tap water. Control rats received no administration of DOCA or NaCl. To investigate the temporal expression profiles of M1- and M2-specific markers for microglia, the animals were subjected to the immunohistochemical and biochemical studies after 2, 3, or 4 weeks DOCA-salt treatment. Results Hypertension occurred after 2 weeks of DOCA and salt administration, when round-shaped microglia with slightly shortened processes were observed juxtaposed to the vessels, although the histopathological findings were normal. After 3 weeks of DOCA and salt administration, M1-state perivascular and parenchyma microglia significantly increased, when local histopathological findings began to be observed but cerebrovascular destruction did not occur. On the other hand, M2-state microglia were never observed around the vessels at this period. Interestingly, prior to M1 activation, about 55% of perivascular microglia transiently expressed Ki-67, one of the cell proliferation markers. Conclusions We concluded that the resting perivascular microglia directly switched to the pro-inflammatory M1 state via a transient proliferative state in DOCA-salt rats. Our results suggest that the activation machinery of microglia in chronic hypertension differs from acute ischemic models. Proliferative microglia are possible initial key players in the development of hypertension-induced cerebral vessel damage. Fine-tuning of microglia proliferation and activation could constitute an innovative therapeutic strategy to prevent its development. Electronic supplementary material The online version of this article (10.1186/s12974-019-1467-7) contains supplementary material, which is available to authorized users.

1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:389-397.

No abstract

Background: Growth plate injuries and disorders cause premature closure, resulting in shortened or deformed limbs. Quantitative assessment by MRI might monitor the status of the growth plate and may assist in the prediction of these deformations. Purpose: To investigate whether the status of the growth plate can be monitored by quantitative evaluation using MRI of the noninjured region of the growth plate in a physeal injury model. Study Type: Prospective, longitudinal. Animal Model: A 3.0-mm drill was used to create an injury to the central region of the right proximal tibial growth plate in 5-week-old male Japanese white rabbits (N = 18). The left tibia served as the control. Field Strength/Sequence: 7.04T, T 2 -weighted imaging, diffusion-weighted imaging. Assessment: Eight of 18 rabbits underwent MRI, proton density-weighted imaging, and T 2 -weighted and diffusion-weighted imaging. T 2 and apparent diffusion coefficient (ADC) maps were generated for each image. The growth plate height and the T 2 and ADC values of the noninjured region were measured. Two rabbits were sacrificed at 2, 4, 6, 8, and 10 weeks postinjury. Proximal tibial bones were evaluated using microcomputed tomography, histological, and immunohistological methods. Statistical Tests: Data were compared using repeated-measures analysis of variance followed by Tukey post-hoc multiple comparison. Results: Growth plate height decreased at 10 weeks postinjury (P = 0.018) on the injured side. T 2 values were greater at 2 weeks postinjury (P = 0.0478) and decreased at 8 and 10 weeks (P = 0.0226, P = 0.0470, respectively) on the injured side. ADC values increased at 6 weeks on the lateral side (P = 0.0304) and decreased at 8 weeks and 10 weeks postinjury (P < 0.01) on the medial and injured sides, respectively. Data Conclusion: Quantitative MRI can help monitor the status of the growth plate and capture its changes early. Level of Evidence: 1 Technical Efficacy: Stage 3

BackgroundArticular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent.MethodsWe induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T2-calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation.ResultsSignificant differences in the SIR and T2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA.ConclusionWe evaluated the SIR and T2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Objectives:The significance of vascularity visualized by Doppler sonography in osteochondritis dissecance (OCD) lesion of the humeral capitellum is unclear. The objectives of this study were twofold: 1) to evaluate the relationship between Doppler ultrasound (US) signals observed in OCD lesion of the humeral capitellum and X-ray stage; 2) to determine if the presence of Doppler US signals in OCD lesion of the humeral capitellum could be the predictor of healing potential.Methods:Fifty patients with OCD of the humeral capitellum treated conservatively were enrolled in this study. During the conservative treatment period, Doppler sonography was performed on affected elbow to assess the presence of vascularity in the OCD lesion (Figure 1), and radiographic examination were evaluated on the same day to determine the X-ray stage (stage I: radiolucent stage, stage II: fragmentation stage, and stage III: loose body stage) of the OCD lesion (Figure 2). Radiographic examination of the elbow was examined after 6 weeks to evaluate the healing of the lesion. If the size of the lesion decreased or new bone formations were observed around the fragments, the healing of the lesion was considered to be improve. The χ2 test was used to determine if the presence of Doppler US signals were related to X-ray stage and the improvement of the healing. P < 0.05 was considered significant for all statistical analyses.Results:The Doppler US signals in OCD lesions were positive in 23 patients and negative in 27 patients. Of these patients, 19 were X-ray stage I, 17 were stage II, and 9 were stage III. The healing of OCD lesions improved in 78.2% for the positive Doppler US signal group, but only 18.5% for the negative Doppler US signal group (Figure 3). The presence of the Doppler US signal was significantly related to the improvement of healing (P = 0.00002). The Doppler US signal were positive in 78.9% for stage I, 36.4% for stage II, and 0.0% for stage III (Figure 4). The presence of Doppler US signal was significantly related to early X-ray stage (P = 0.0002).Conclusion:From this study, the presence of vascularity in the OCD lesion of the humeral capitellum is important for the improvement of healing during the conservative treatment period. The vascularity visualized by Doppler sonography could be a useful predictor for healing potential of the OCD of the humeral capitellum when treated conservatively.

Objectives:The aim of this study was to investigate the experience rate of elbow pain and to clarify the relationship between morphological abnormality of the humeral medial epicondyle and positions among baseball players in elementary school (ES), junior high school (JHS) and high school (HS).Methods:In this study, 4353 baseball players who participated in our medical screening (2008-2015) were enrolled. There were 1545 players from ES, 1934 players from JHS, and 874 players from HS. We asked them to answer the questionnaire to investigate the experience of elbow pain, and the position they played. Ultrasonography of the humeral medial epicondyle was examined and irregularity, fragmentation, and malunion of the humeral medial epicondyle. The results were analyzed statistically. P < 0.05 was considered significant for all statistical analyses.Results:The experience rates of elbow pain among players in ES, JHS, and HS were 26.0%, 27.0%, and 68.3%. The rates of abnormality of humeral medial epicondyle among players in ES, JHS, and HS were 18.2%, 36.3%, and 39.9% (Table 1). The experience rate of elbow pain among pitchers and catchers was significantly higher than the fielders in ES (Table 2), however, there were no significant differences between positions in JHS and HS (Table 3,4). According to the rate of morphological abnormalities of humeral medial epicondyle, pitchers and catchers were significantly higher than fielders in ES, while only pitchers were significantly higher than the fielders in JHS and HS (Table 2,3,4).Conclusion:The experience rate of elbow pain among baseball players rose as the age increased, and the rate in HS was almost 70%. The rates of morphological abnormality of humeral medial epicondyle among pitchers and catchers were high and the tendency was observed from a young age. The primary prevention of elbow injuries in youth baseball players of all ages should be considered.