Imaging of Perirenal and Intrarenal Lymphatic Vessels: Anatomy-based Approach.

The lymphatic system (or lymphatics) consists of lymphoid organs and lymphatic vessels. Despite the numerous previously published studies describing conditions related to perirenal and intrarenal lymphoid organs in the radiology literature, the radiologic findings of conditions related to intrarenal and perirenal lymphatic vessels have been scarcely reported. In the renal cortex, interlobular lymphatic capillaries do not have valves; therefore, lymph can travel along the primary route toward the hilum, as well as toward the capsular lymphatic plexus. These two lymphatic pathways can be opacified by contrast medium via pyelolymphatic backflow at CT urography, which reflects urinary contrast agent leakage into perirenal lymphatic vessels via forniceal rupture. Pyelolymphatic backflow toward the renal hilum should be distinguished from urinary leakage due to urinary injury. Delayed subcapsular contrast material retention via pyelolymphatic backflow, appearing as hyperattenuating subcapsular foci on CT images, mimics other subcapsular cystic diseases. In contrast to renal parapelvic cysts originating from the renal parenchyma, renal peripelvic cysts are known to be of lymphatic origin. Congenital renal lymphangiectasia is mainly seen in children and assessed and followed up at imaging. Several lymphatic conditions, including lymphatic leakage as an early complication and acquired renal lymphangiectasia as a late complication, are sometimes identified at imaging follow-up of kidney transplant. Lymphangiographic contrast material accumulation in the renal hilar lymphatic vessels is characteristic of chylo-urinary fistula. Chyluria appears as a fat-layering fluid-fluid level in the urinary bladder or upper urinary tract. Recognition of the anatomic pathway of tumor spread via lymphatic vessels at imaging is of clinical importance for accurate management at oncologic imaging. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement: Rationale and Design of the ENBALV Trial.

BACKGROUND AND PURPOSE: Anticoagulant therapy with vitamin K antagonists is recommended within 3 to 6 months after bioprosthetic valve replacement to prevent thromboembolic events. However, data regarding whether direct oral anticoagulants can be an alternative to warfarin in such patients are limited. The purpose of this study is to compare the efficacy and safety of edoxaban versus warfarin within 3 months after bioprosthetic valve replacement. METHODS: The ENBALV trial is an investigator-initiated, phase 3, randomized, open-label, multicenter study. It involves patients aged 18 to 85 years undergoing bioprosthetic valve replacement at the aortic and/or mitral position. They are randomized 1:1 to receive either edoxaban or warfarin. Administration of edoxaban or warfarin is to be continued for 12 weeks after surgery. The primary outcome is the occurrence rate of stroke or systemic embolism at 12 weeks after surgery. The net clinical outcome is a composite of stroke, systemic embolism, or major bleeding, which is included in the secondary outcomes. CONCLUSION: The ENBALV trial demonstrates the efficacy and safety of edoxaban compared with warfarin in patients early after bioprosthetic valve replacement, including patients with sinus rhythm, which will bring a significant benefit to patients in clinical practice. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) 2051210209. 30 Mar 2022 https://jrct.niph.go.jp/latest-detail/jRCT2051210209 .

LC-MS/MS analysis of elastin crosslinker desmosines and microscopic evaluation in clinical samples of patients with hypertrophy of ligamentum flavum.

Ligamentum flavum (LF) pathologies often lead to severe myelopathy or radiculopathy characterized by reduced elasticity, obvious thickening, or worsened ossification. Elastin endows critical mechanical properties to tissues and organs such as vertebrae and ligaments. Desmosine (DES) and isodesmosine (IDES) are crosslinkers of elastin monomers called tropoelastin. These crosslinkers are potential biomarkers of chronic obstructive pulmonary disease. As a biological diagnostic tool that supplements existing symptomatic, magnetic resonance imaging scanning or radiological imaging diagnostic measures for LF hypertrophy and associated pathologies, an isotope-dilution liquid chromatography-tandem mass spectrometry method with selected reaction monitoring mode for the quantitation of DESs in human plasma, urine, cerebrospinal fluid (CSF), and yellow ligamentum was investigated. Isotopically labeled IDES-13C3,15N1 was used as an internal standard (ISTD) for DES quantitation for the first time. The samples plus ISTD were hydrolyzed with 6 N hydrochloric acid. Analytes and ISTD were extracted using a solid phase extraction cellulose cartridge column. The assays were repeatable, reproducible, and accurate with % CV ≤ 7.7, ISTD area % RSD of 7.6, and % AC ≤ (101.2 ± 3.90) of the calibrations. The ligamentum samples gave the highest average DES/IDES content (2.38 µg/mg) on a dry-weight basis. A high percentage of the CSF samples showed almost no DESs. Urine and plasma samples of patients showed no significant difference from the control (p-value = 0.0519 and 0.5707, respectively). Microscopy of the yellow ligamentum samples revealed dark or blue-colored zones of elastin fibers that retained the hematoxylin dye and highly red-colored zones of collagen after counterstaining with van Gieson solution. Thus, we successfully developed a method for DES/IDES quantitation in clinical samples.

Effect of cyborg-type robot Hybrid Assistive Limb on patients with severe walking disability in acute stroke: A randomized controlled study.

OBJECTIVES: To investigate whether early gait training using Hybrid Assistive Limb (HAL) is feasible and improves walking and independency compared with conventional physical therapy (CPT) in patients with severe walking disability after stroke. METHODS: We conducted a single-center, randomized controlled study. Patients with first-ever stroke who had severe walking disability were included. All patients started gait training within 10 days post-stroke onset. Twenty-four patients were randomly assigned into HAL or CPT groups. Outcome measures were collected at three time points, at baseline, completion of 20 sessions of gait training (second assessment), and 3 months after the initiation of gait training. The primary outcomes were changes in motor sub-scores of the Functional Independence Measure or Functional Ambulation Category at the completion of the second assessment from baseline. RESULTS: Twenty-two patients (median age, 68 years; 12 patients in the HAL group and 10 patients in the CPT group) completed the study. There were no significant differences in primary outcomes. Apathy scale, one of the secondary outcomes, showed a decreasing trend in the HAL group (mean change of -3.8, 95% CI -8.14 to 0.475), and a slight increasing trend in the CPT group (mean change of 1.2, 95% CI -2.66 to 5.06) at the second assessment. Patients in the HAL group experienced no adverse events. CONCLUSIONS: Early gait training in patients with severe walking disability after stroke using HAL was feasible. Walking ability and independency were not improved at the completion of 20 sessions of gait training.

Correction: Takeuchi et al. Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation. Medicina 2022, 58, 1868.

In the original publication [...].

Niclosamide downregulates LOX-1 expression in mouse vascular smooth muscle cells and changes the composition of atherosclerotic plaques in ApoE-/- mice.

Genetic lineage tracing studies have shown that phenotypic switching of vascular smooth muscle cells (VSMCs) results in less-differentiated cells, including macrophage-like cells that lack traditional VSMC markers. This switching contributes to the formation of necrotic core in plaques and promotes atherosclerosis, which is important for plaque stability. Niclosamide, a commonly used anti-helminthic drug, has recently attracted attention as an anti-cancer drug that inhibits multiple signaling pathways. The expression of the S100A4 protein is upregulated in synthetic VSMCs and inhibited by niclosamide on metastatic progression in colon cancer. We aimed to test the effect of niclosamide on VSMC phenotype switching and plaque stability. To examine murine atherosclerosis, we induced experimental lesions by blood flow cessation in apolipoprotein E knockout mice fed a high-fat diet. Oral administration of niclosamide changed 4-week-old plaques to collagen-rich and less-necrotic core phenotypes and downregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in vivo. In vitro analysis indicated that niclosamide reduced LOX-1 expression in VSMCs in a concentration-dependent and S100A4-independent manner. The inhibitory effect of niclosamide on LOX-1 and collagen type I was associated with the inactivation of the nuclear factor-κB signaling pathway. We demonstrated that the administration of niclosamide reduced LOX-1 expression and altered the composition of murine carotid plaques. Our results highlight the potential of niclosamide as an atheroprotective agent that enhances atherosclerotic plaque stability.

Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation.

Background and Objectives: Condoliase, a chondroitin sulfate ABC endolyase, is a novel and minimally invasive chemonucleolytic drug for lumbar disc herniation. Despite the growing number of treatments for lumbar disc herniation, the predicting factors for poor outcomes following treatment remain unclear. The aim of this study was to determine the predictive factors for unsuccessful clinical outcome following condoliase therapy. Material and Methods: We performed a retrospective single-center analysis of 101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p < 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715−1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration.

Pelvic arterial embolisation with cyanoacrylate during caesarean hysterectomy for placenta accreta.

PURPOSE: To compare n-butyl cyanoacrylate (NBCA) and gelatine sponge (GS) as embolic materials for prophylactic pelvic arterial embolisation during caesarean hysterectomy for placenta accreta spectrum (PAS). MATERIAL AND METHODS: This retrospective study comprised 12 women (age range, 23-42 years; mean, 34.1 years) who underwent caesarean hysterectomy for PAS. Following caesarean delivery, bilateral uterine and non-uterine parasitic arteries were embolized with GS in the first four cases (GS group) and primarily with NBCA mixed with iodized oil in the subsequent eight cases (NBCA group). Procedure time for embolisation and hysterectomy and total blood loss were compared between the two groups using Welch's t-test. RESULTS: Although procedure time for embolisation tended to be longer in the NBCA group than in the GS group (111 ± 47 min versus 71 ± 32 min, p=.11), that for hysterectomy was significantly reduced in the NBCA group when compared to the GS group (158 ± 42 min versus 236 ± 39 min, p=.02). Total blood loss was significantly lower in the NBCA group than in the GS group (1375 ± 565 mL versus 2668 ± 587 mL, p=.01). CONCLUSION: Procedure time for hysterectomy and total blood loss during caesarean hysterectomy can be reduced by using NBCA instead of GS in prophylactic pelvic arterial embolisation for PAS.

Severe low back pain with mild leg symptoms due to lumbar spine stenosis.

BACKGROUND: Some patients with lumbar spine stenosis (LSS) have severe low back pain (LBP) with only mild leg symptoms. The effects of decompression surgery for such patients remain unknown. METHODS: Of 818 patients with LSS who underwent surgical treatment in our institution from 2011 to 2019, eight patients had a numeric rating scale (NRS) score of ≥7 for LBP and 3≤ for leg pain. The patients' age, sex, clinical characteristics, preoperative leg symptoms, and level of LSS were investigated. The detailed characteristics of LBP, such as the disease duration, location of LBP, and exacerbating factors, were obtained from each patient. The NRS and Japanese Orthopaedic Association (JOA) scores for LBP were evaluated on admission, at 1 and 3 months postoperatively, and at the final follow-up (>1 year postoperatively). RESULTS: All patients were male with a mean age of 71.5 years (range, 57-82 years). LBP was exacerbated during walking in six patients and during an extension posture in three patients. The median duration of LBP was 2.9 years (range, 0.3-7 years). The stenosis was located at L2/3 in three patients, L3/4 in five patients, and L4/5 in seven patients. The stenosis involved one level in three patients and more than two levels in five patients. Other pathologies, such as sacroiliac joint lesions, facet pain, superior/middle cluneal nerve pain, and discogenic pain, were excluded by diagnostic anesthetic block and detailed physical examination. All patients underwent posterior decompression surgery without fusion. In all eight patients, the NRS score for LBP significantly improved from 7.6 (range, 7-10) to 1.7 (range, 0-3) and the JOA score improved from 13.1 (range, 4-19) to 21.8 (range, 18-27). CONCLUSION: A low proportion of patients showed walking-evoked severe LBP with mild leg symptoms due to lumbar spine stenosis. The patients' pain was improved by decompression surgery with satisfactory results.

[What are the Indications and Points of Anterior Cervical Decompression Surgery?]

Anterior cervical foraminotomy is a motion-preserving and precise decompressing surgery with minimal bone removal. As preserving the motion segment and maximizing decompression are contradictory concepts, proficiency is needed to balance these requirements. Anatomical knowledge and good intraoperative orientation are essential to reach the nerve roots accurately in a narrow surgical field.

[False-Positive ¹²³I-Metaiodobenzylguanidine Scan in a Patient with Adrenocortical Cancer].

A 59-year-old woman presented with a left adrenal tumor 4 cm in diameter. The ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy showed apparent accumulation in the left adrenal tumor. However, the patient had no sign or symptoms suggesting pheochromocytoma. No biochemical evidence of catecholamine excess was noticed. Computed tomography (CT) revealed relatively strong enhancement in the arterial phase, which persisted until the portal phase. The computed tomography (CT) and magnetic resonance imaging showed 2 liver nodule suspected to be metastatic tumors. No ¹²³I-MIBG accumulation was seen in these nodules. CT also showed thyroid nodules with calcification, which suggested papillary thyroid cancer. Based on the findings, open left adrenalectomy, partial hepatectomy and segmentectomy were performed under the clinical diagnosis of pheochromocytoma and metastatic liver tumors. Histopathological diagnosis was adrenocortical cancer. There was only lymphocyte infiltration in the liver nodules. Postoperative recovery was uneventful, and the patient underwent partial thyroidectomy 6 months later. The pathological diagnosis was papillary thyroid cancer. She has been without recurrence or metastases for 18 months after adrenalectomy. We found only 6 cases of MIBG scintigraphy-positive adrenocortical cancer in the literature. The mechanisms for MIBG uptake in adrenocortical cancer are discussed with a review of the literature.

Urgent Proton Beam Therapy With Interinstitutional Transfer for Patients With Intracranial Rhabdomyosarcoma: Report of 3 Cases.

A number of cases have been reported in recent years regarding the use of proton beam therapy to mitigate adverse events affecting important cranial organs in cases of rhabdomyosarcoma at parameningeal sites. However, few reports have described the use of proton beam therapy as urgent radiotherapy for parameningeal rhabdomyosarcoma with intracranial extension. We treated 3 patients diagnosed with parameningeal rhabdomyosarcoma extending into the cranium who were assessed at other hospitals as suitable for urgent radiotherapy and transferred to our hospital for proton beam therapy. These patients comprised 2 boys and 1 girl 6 to 12 years of age at diagnosis, and proton beam therapy was started on days 5, 11, and 23 after diagnosis, respectively. Patients with parameningeal rhabdomyosarcoma extending into the cranium can be transferred to institutions equipped to perform proton beam therapy. To minimize the interval to starting therapy, medical information should be shared with institutions capable of providing such therapy as soon as the possibility of intracranial soft-tissue sarcoma is recognized. Proton beam therapy is 1 option for radiotherapy in cases of intracranial rhabdomyosarcoma.

Treatment margins in radiotherapy for liver tumors visualized as T2*-hypointense areas on SPIO-enhanced MRI at 9.4 T.

OBJECTIVE: To investigate whether a SPIO-labeling technique could enable MR visualization of the treatment margin after X-irradiation at a single dose of 30 Gy. MATERIALS AND METHODS: Fifteen rats bearing N1-S1 hepatoma in either the left (group 1) or right (group 2) liver lobe were examined. Four hours after systemic SPIO administration, the left lobe was selectively irradiated at 30 Gy. Liver T2* maps were acquired 7 days later using a 9.4 T scanner. The livers were excised and examined histologically. RESULTS: The irradiated area showed T2*-weighted hypointensity with significantly shorter T2* values than those in the non-irradiated area (p < 0.001). Tumors in group 1 completely disappeared, whereas tumors in group 2 had grown outside the T2*-weighted hypointensity by up to ~ 2.3 times that at baseline. Group 1 showed significantly higher probability of tumor regression than group 2 (p = 0.048). Histologically, iron deposition was heavier in irradiated areas than in non-irradiated areas. DISCUSSION: Even at a single dose of 30 Gy, which is a slightly higher dose than can be used clinically in stereotactic body radiotherapy, MR visualization of the treatment margin was achieved, because tumors showed significant growth outside the T2*-hypointense areas. In contrast, tumors disappeared inside the T2*-hypointense areas.

Extraforaminal entrapment of the fifth lumbar spinal nerve by nearthrosis in patients with lumbosacral transitional vertebrae.

PURPOSE: Lumbosacral transitional vertebrae (LSTV) often have nearthrosis between the L5 transverse processes and the sacral ala; this causes the formation of new bone and synovial-like tissue, which can entrap L5 nerve root. The present study aimed to examine the role of nearthrosis in L5 nerve root compression in patients with LSTV. METHODS: From 2008 to 2018, 65 patients were surgically treated for severe leg pain/numbness caused by L5 extraforaminal stenosis. The patients were assessed regarding the presence of LSTV, radiographic features of nearthrosis, operative/radiological findings, and clinical outcomes. CT/MRI were used to classify the patients into three groups: group A had L5 nerve root compression that was not related to nearthrosis, group B had L5 nerve root impingement due to nearthrosis with new bone formation, and group C had L5 nerve root impingement due to nearthrosis with synovial-like tissue. The relationships between the type of LSTV (based on the Castellvi's classification) and these three groups were investigated. RESULTS: Although 26 of 65 patients had LSTV (40%), four were excluded because of less than 1-year follow-up. The 22 patients with LSTV were classified as type IA (n = 2), IIA (n = 13), and IIB (n = 7). In accordance with the radiological findings, there were eight patients in group A, six in group B, and eight in group C; the LSTV morphology did not significantly differ between groups. CONCLUSIONS: L5 nerve root was compressed by nearthrosis in 64% of symptomatic patients with LSTV; this region should be carefully assessed in all symptomatic patients with LSTV.

EP4 receptor-associated protein regulates gluconeogenesis in the liver and is associated with hyperglycemia in diabetic mice.

Prostaglandin E2 receptor 4-associated protein (EPRAP) is a key molecule in suppressing inflammatory responses in macrophages. EPRAP is expressed not only in macrophages but also in hepatocytes; however, the role of EPRAP in hepatocytes has not yet been defined. To examine the physiological role of hepatic EPRAP in mice, we performed the glucose tolerance test and the hyperinsulinemic-euglycemic clamp in high-fat sucrose diet (HFSD)-fed wild-type (WT) and Eprap null mice. We evaluated the contribution of EPRAP to gluconeogenesis by pyruvate tolerance test and primary hepatocyte experiments. Furthermore, lentivirus-expressing Eprap-specific small-hairpin RNA was injected in db/ db mice. HFSD-fed Eprap null mice had significantly lower blood glucose levels than HFSD-fed WT mice. Eprap null mice also had low glucose levels after fasting or pyruvic acid injection. Moreover, primary hepatocytes from Eprap-deficient mice showed decreased glucose production and lower expression of the Phosphoenol pyruvate carboxykinase and Glucose 6-phosphatase genes. Lentivirus-mediated hepatic Eprap suppression decreased glucose levels and the expression of gluconeogenic genes in db/ db mice. We conclude that EPRAP regulates gluconeogenesis in hepatocytes and is associated with hyperglycemia in diabetic mice. Our data suggest that suppression of EPRAP could be a novel strategy for the treatment of diabetes.

Near-Infrared Imaging Using Intravenous Indocyanine Green at a Conventional Dose to Locate Pulmonary Metastases: A Pilot Study.

Intravenous indocyanine green (ICG) has been reported to localize intra-abdominal metastatic lesions in several clinical trials. Our pilot study aimed to investigate the feasibility and safety of ICG fluorescence localization in pulmonary metastasectomy using a near-infrared fluorescence thoracoscope. Each patient received intravenous 0.25 or 0.5 mg/kg of ICG. The maximum diameter of the tumor on computed tomography ranged from 0.5 to 3.5 (median: 1.15) cm. Intravenous ICG injection localized pulmonary metastases in a portion (3 patients) of the enrolled patients. Our preliminary results provided us with important information to modify the study protocol.

Change in MRI findings of medial collateral ligament injury in adolescent baseball players with no clinical symptoms over time.

OBJECTIVE: Elbow screening of adolescent baseball players began in 2014 using ultrasound, palpation, and dedicated magnetic resonance imaging (MRI). We frequently encountered subjects showing MCL injury on MRI but no clinical symptoms. We assessed variations in asymptomatic MCL injury findings at follow-up MRI, and clarified the pathogenesis of these findings. MATERIALS AND METHODS: Using a 0.2-T-dedicated MRI, 30 subjects with asymptomatic MCL injury at initial MRI who agreed to follow-up MRI were included. We classified the findings at repeat MRI as follows: (a) disappeared, (b) better, and (c) worse. RESULTS: There were 6, 16, and 8 subjects in groups a, b, and c, respectively. The average age at follow-up was 14.0, 12.1, and 12.4 years in groups a, b, and c, respectively. There were significant differences between groups a and b and between groups a and c. Average height at follow-up of groups a, b, and c was 1.64, 1.52, and 1.57 cm, respectively, with a statistically significant difference between groups a and b. The average size of the short axis of the MCL of subjects in group a was 2.0 cm on the dominant side and 1.5 cm on the contradominant side (P < 0.04). CONCLUSION: Players with asymptomatic MCL injury can continue to play baseball with no limitations, as these findings usually disappear around the age of 14.0 years, when the growth spurt occurs. This finding may be a precursor of 'adaptation', which is generally observed in high school baseball players, suggesting that the MCL adapts as growth occurs.

Imaging mass spectroscopy delineates the thinned and thickened walls of intracranial aneurysms.

OBJECT: The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA. MATERIAL AND METHODS: IAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode. RESULTS: A molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography-tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs. CONCLUSIONS: Our study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall.

Deficiency in EP4 Receptor-Associated Protein Ameliorates Abnormal Anxiety-Like Behavior and Brain Inflammation in a Mouse Model of Alzheimer Disease.

Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor-associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20+/- onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20+/-EPRAP+/+ and J20+/-EPRAP-/- mice. EPRAP deficiency reversed the reduced anxiety of J20+/- mice but did not affect hyperactivity. No differences in spatial memory were observed between J20+/-EPRAP+/+ and J20+/-EPRAP-/- mice. In comparison with J20+/-EPRAP+/+, J20+/-EPRAP-/- mice exhibited less microglial accumulation and reductions in the Cd68 and tumor necrosis factor-α mRNAs in the prefrontal cortex and hippocampus. No significant differences were found between the two types of mice in the amount of amyloid-ß 40 or 42 in the cortex and hippocampus. J20+/-EPRAP-/- mice reversed the reduced anxiety-like behavior and had reduced microglial activation compared with J20+/-EPRAP+/+ mice. Further research is required to identify the role of EPRAP in AD, but our results indicate that EPRAP may be related to behavioral and psychological symptoms of dementia and inflammation in patients with AD.