Malignant Transformation of Unknown Duration of an Ovarian Mature Cystic Teratoma Presenting as a Trocar Recurrence in a Young Patient: A Case Report and Literature Review.

Although laparoscopic cystectomy is a safe and effective management strategy for ovarian mature cystic teratoma (MCT) in pediatric and adolescent patients, it has been challenged because of its association with a higher risk of intraoperative spillage leading to chemical peritonitis, adhesion formation, and iatrogenic implantation of malignant cells. Here, we report a rare case of a 23-year-old female patient with MCT tissue during laparoscopic ovarian cystectomy that remained in the peritoneum, possibly becoming malignant thereafter. Intraoperatively, the cyst's contents leaked into the abdominal cavity. The abdominal cavity was thoroughly cleaned before the operation was completed. Pathological examination revealed an MCT without malignant findings. The patient's postoperative course was uneventful. Although the excised tissue was benign, the patient presented with a mass at the trocar wound (upper suprapubic area) 2 years after initial surgery. Biopsy results indicated squamous cell carcinoma. Moreover, peritoneal and bladder invasions were diagnosed. She subsequently experienced symptoms of cancerous peritonitis. Achieving a complete cure through surgery alone was deemed difficult; however, successful neoadjuvant chemotherapy and tumor reduction surgery kept her alive up until the publication of this case report, 3 years since diagnosis with squamous cell carcinoma. This case indicates that malignant transformation of MCTs can occur at any age.

Characterization of human Ccser2 as a protein tracking the plus-ends of microtubules.

OBJECTIVE: Microtubules, which are closely related to cell proliferation, have been the promising therapeutic target of cancer. Therefore, it is necessary to understand the intracellular control mechanisms of microtubules, the whole picture of which is still unclear though. Intracellular dynamics of microtubules are regulated by various microtubule-associated proteins, one group of which is microtubule plus-end-tracking proteins (+ TIPs), localizing to the extending tips of microtubules. Here, we report the identification and analysis of Ccser2 as a new + TIP in human breast cancer MCF-7 cells. RESULTS: Ccser2 was found to be a member of + TIPs by microscopic observations including time-lapse imaging. The C-terminal region of Ccser2, including two SxIP motifs, was likely to be important for the tracking function. In MCF-7 cells, endogenous Ccser2 was mainly detected in the peripheral regions of microtubule fibers, suggesting that Ccser2 functions in cell projections.

Endovascular therapy for intracranial infectious aneurysms associated with a left ventricular assist device: illustrative case.

BACKGROUND: Cerebrovascular events and infection are among the most common complications of left ventricular assist device (LVAD) therapy. The authors reported on a patient with an infectious intracranial aneurysm (IIA) associated with LVAD infection that was successfully occluded by endovascular therapy. OBSERVATIONS: A 37-year-old man with severe heart failure received an implantable LVAD. He was diagnosed with candidemia due to driveline infection 44 months after LVAD implantation, and empirical antibiotic therapy was started. After 4 days of antibiotic treatment, the patient experienced sudden dizziness. Computed tomography (CT) revealed subarachnoid hemorrhage in the right frontal lobe, and CT angiography revealed multiple aneurysms in the peripheral lesion of the anterior cerebral artery (ACA) and middle cerebral artery. Two weeks and 4 days after the first bleeding, aneurysms on the ACA reruptured. Each aneurysm was treated with endovascular embolization using n-butyl cyanoacrylate. Subsequently, the patient had no rebleeding of IIAs. The LVAD was replaced, and bloodstream infection was controlled. He received a heart transplant and was independent 2 years after the heart transplant. LESSONS: LVAD-associated IIAs have high mortality and an increased risk of surgical complications. However, endovascular obliteration may be safe and thus improve prognosis.

Noninvasive prenatal testing suggesting an abnormality in chromosome 15 confirmed to be a case of Prader-Willi syndrome caused by trisomy rescue in the neonatal period.

We report a case of a neonatal diagnosis of Prader-Willi syndrome caused by uniparental disomy. A 34-year-old pregnant woman underwent noninvasive prenatal testing (NIPT) in a hospital that was not certified by the Japanese Association of Medical Sciences. The results of trisomy 13, 18, and 21 were negative; however, a possible abnormality in chromosome 15 was indicated by the Z-score. Genetic counseling was not performed; thus, the woman did not understand the implication of this result. Therefore, she continued with the pregnancy and delivered a boy weighing 1892 g with hypogonadism at 38 weeks and 5 days. The infant was diagnosed with Prader-Willi syndrome caused by uniparental disomy derived from trisomy rescue. The NIPT results may have reflected placental mosaicism, emphasizing the importance of understanding the limitations of NIPT due to the presence of congenital chromosomal abnormalities that cannot be detected by NIPT platforms.

Lessons Learned from Mechanical Thrombectomy of an Acute Occlusion of a Duplicated Middle Cerebral Artery: A Case Report.

Objective: Detection of acute arterial occlusion in an anomalous middle cerebral artery (MCA) is challenging in an emergency setting because of its rarity. Case Presentation: We report an 81-year-old woman who presented with acute occlusion of a duplicated middle cerebral artery (DMCA). Although the absence of the superior trunk of the left MCA was identified on preoperative imaging, initial angiography showed no typical sign of the occluded vessel. Repeated angiography eventually revealed retrograde arterial flow parallel to the other visible MCA trunk, which raised the possibility of a DMCA. The occlusion occurred at the origin of the DMCA originating from the internal carotid artery terminus, which obscured its presence. Mechanical thrombectomy was performed and achieved complete recanalization. The DMCA had two trunks of approximately equal size. The patient completely recovered within 90 days. Conclusion: Comprehensive knowledge of cerebrovascular anomalies is essential to identify the occluded branch faster and accurately and to avoid thrombectomy-related complications in endovascular recanalization therapy. Relevant DMCA anatomy and tips for identifying an occluded DMCA are discussed.

Efficacy of combined use of a stent retriever and aspiration catheter in mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: The efficacy of combined stent retriever (SR) and aspiration catheter (AC; combined technique: CBT) use for acute ischemic stroke (AIS) is unclear. We investigated the safety and efficacy of single-unit CBT (SCBT)-retrieving the thrombus as a single unit with SR and AC into the guide catheter-compared with single use of either SR or contact aspiration (CA). METHODS: We analysed 763 consecutive patients who underwent mechanical thrombectomy for AIS between January 2013 and January 2020, at six comprehensive stroke centers. Patients were divided into SCBT and single device (SR/CA) groups. The successful recanalization with first pass (SRFP) and other procedural outcomes were compared between groups. RESULTS: Overall, 240 SCBT and 301 SR/CA (SR 128, CA 173) patients were analyzed. SRFP (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2c, 43.3% vs 27.9%, p<0.001; mTICI 3, 35.8% vs 25.5%, p=0.009) and final mTICI ≥2b recanalization (89.1% vs 82.0%, p=0.020) rates were significantly higher, puncture-to-reperfusion time was shorter (median (IQR) 43 (31.5-69) vs 55 (38-82.2) min, p<0.001), and the number of passes were fewer (mean±SD 1.72±0.92 vs 1.99±1.01, p<0.001) in the SCBT group. Procedural complications were similar between the groups. In subgroup analysis, SCBT was more effective in women, cardioembolic stroke patients, and internal carotid artery and M2 occlusions. CONCLUSIONS: SCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.

Protein Nanoparticles Modified with PDGF-B as a Novel Therapy After Acute Cerebral Infarction.

Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs (HSPNPs) to examine its therapeutic effect in cerebral infarction. PDGF-B modified HSPNPs (PDGF-B HSPNPs) were injected 1 d after transient middle cerebral artery occlusion (t-MCAO) in CB-17 model mice. We analyzed the infarct volume and motor functional recovery at 3 and 7 d. PDGF-B HSPNPs were specifically distributed in the infarct area, and compared with HSPNPs alone, they significantly reduced infarct volumes and improved neurologic function 3 and 7 d after administration. PDGF-B HSPNP administration was associated with strong phosphorylation of Akt in infarct areas and significantly increased neurotrophin (NT)-3 production as well as reduced cell apoptosis compared with HSPNPs alone. Moreover, astrogliosis in peri-infarct area was significantly upregulated with PDGF-B HSPNPs compared with HSPNPs alone. Treatment with PDGF-B HSPNPs might be a novel approach for treating cerebral infarction.

Safety and Efficacy of Edonerpic Maleate for Patients With Mild to Moderate Alzheimer Disease: A Phase 2 Randomized Clinical Trial.

IMPORTANCE: Edonerpic maleate (T-817MA) protects against Aß40-induced neurotoxic effects and memory deficits, promotes neurite outgrowth, and preserves hippocampal synapses and spatial memory in tau transgenic mice. These effects may be mediated via sigma-1 receptor activation, delivery of synaptic AMPA receptors, or modulation of microglial function and may benefit patients with Alzheimer disease. OBJECTIVE: To assess the efficacy, safety, and tolerability of edonerpic for patients with mild to moderate Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial conducted over 52 weeks from June 2, 2014, to December 14, 2016, at 52 US clinical and academic centers. Of 822 outpatients screened, 484 met the following criteria and were randomly assigned to treatment: 55 to 85 years of age, probable Alzheimer disease, Mini-Mental State Examination scores from 12 to 22, and taking stable doses of donepezil or rivastigmine with or without memantine. INTERVENTIONS: Random assignment (1:1:1 allocation) to placebo or 224 mg or 448 mg of edonerpic maleate, once per day. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were scores on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinical Impression of Change (ADCS-CGIC) at week 52. Biomarkers were brain, lateral ventricular, and hippocampal volumes, as determined on magnetic resonance imaging, and cerebrospinal fluid Aß40, Aß42, total tau, and phospho-tau181. The primary efficacy analysis was performed on the coprimary end points for the modified intention-to-treat population. RESULTS: Of 482 participants in the safety population, 140 of 158 participants (88.6%) assigned to placebo, 117 of 166 participants (70.5%) to 224 mg of edonerpic maleate, and 120 of 158 participants (76.0%) to 448 mg of edonerpic maleate completed the trial. The mean ADAS-cog score change at week 52 was 7.91 for the placebo group, 7.45 for the 224-mg group, and 7.08 for the 448-mg group. Mean differences from placebo were -0.47 (95% CI, -2.36 to 1.43; P = .63) for the 224-mg group and -0.84 (95% CI, -2.75 to 1.08; P = .39) for the 448-mg group. Mean ADCS-CGIC scores were 5.22 for the placebo group, 5.24 for the 224-mg group, and 5.25 for the 448-mg group, with mean differences from placebo of 0.03 (95% CI, -0.20 to 0.25; P = .81) for the 224-mg group and 0.04 (95% CI, -0.19 to 0.26; P = .76) for the 448-mg group. In the safety population, a total of 7 of 158 participants (4.4%) in the placebo group, 23 of 166 participants (13.9%) in the 224-mg group, and 23 of 158 participants (14.6%) in the 448-mg group discontinued because of adverse events. The most frequent adverse events were diarrhea and vomiting. CONCLUSIONS AND RELEVANCE: Edonerpic maleate appeared to be safe and tolerable, with expected gastrointestinal symptoms occurring early but without evidence for a clinical effect among patients with mild to moderate Alzheimer disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02079909.

PulseRider-Assisted Coil Embolization for Treatment of Intracranial Bifurcation Aneurysms: A Single-Center Case Series with 24-Month Follow-up.

BACKGROUND: Although endovascular coiling of unruptured aneurysms is widely accepted, the endovascular treatment of wide-neck bifurcation aneurysms remains one of the most challenging morphologies. Our purpose was to describe our experience with 24-month follow-up for the treatment of unruptured intracranial bifurcation aneurysms using the PulseRider (Cerenovus, New Brunswick, NJ). METHODS: This study is a single-center, single-arm registry performed under institutional review board control to evaluate efficacy and safety of the PulseRider. Patients with bifurcation aneurysms were identified and enrolled prospectively. Angiography immediately after treatment and at 6 months, and magnetic resonance imaging and magnetic resonance angiography at 12- and 24-month follow-up were retrospectively analyzed. A modified Rankin score was obtained prior to procedure, at discharge, and at 6-, 12- and 24-month follow-up visits. RESULTS: Eight patients with a mean age of 66 years were treated with the PulseRider. All patients had bifurcation aneurysms (2 anterior communicating, 2 carotid terminus, and 4 basilar apex). The aneurysm diameters ranged from 4.6 to 13.6 mm (mean 7.4 mm) with dome/neck ratio ranging from 1.4 to 2.2 (mean 1.6). In all cases, the PulseRider was successfully deployed. Complete occlusion was demonstrated at 6-month follow-up on 6 of 8 (75%), near complete occlusion in 1 of 8 (12.5%), and residual aneurysm in 1 of 8 (12.5%) patients. There was no change or recurrence on magnetic resonance angiography, nor clinical complication after the procedure through 24-month follow-up. CONCLUSIONS: Our experience with 24-month follow-up demonstrated favorable efficacy in the treatment of intracranial wide-neck bifurcation aneurysms using the PulseRider.

CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage.

Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.

Pediatric ganglioglioma with an H3 K27M mutation arising from the cervical spinal cord.

The 2016 edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced "diffuse midline glioma H3 K27M mutant" as a new diagnostic entity. These tumors predominately affect pediatric patients and arise from midline structures such as the brainstem, thalamus and spinal cord. Here, we report a rare patient with spinal ganglioglioma carrying an H3 K27M mutation. A 10-year-old boy presented with an intramedullary tumor in the cervical spinal cord. The lesion was partially removed and histologically diagnosed as ganglioglioma. After the remnant tumor grew within 3 months after surgery, the patient underwent radiotherapy. Genetic analyses revealed an H3F3A K27M mutation but no other genetic alterations such as IDH and BRAF mutations. This case may point to pathological heterogeneity in gliomas with H3 K27M mutations.

[Two Cases of Ruptured Blood Blister-like Aneurysm Treated with X-ray Angiography Perfusion(XAP)Analysis].

Two cases of ruptured blood blister-like internal carotid artery aneurysms for which low flow bypass was sufficient to attain successful treatment of trapping are reported. In the acute stage of rupture, it is troublesome to perform accurate examinations of tolerance to ischemia like balloon occlusion test(BOT)for estimating the required amount of bypass flow. In our cases, X-ray angiography perfusion(XAP)analysis was introduced, which could be performed in a couple dozen seconds without room-to-room transfer of patients, following the ordinary examination of diagnostic digital subtraction angiography. The perfusion index(PI)ratio measured in this analysis is equivalent to the laterality of cerebral blood flow between the right and left hemispheres. The PI ratio of 0.85 approximately corresponds to the mean stump pressure(MSTP)of 40mmHg, on the basis of the correlation diagram between the PI ratio and MSTP(approximate straight line:PI ratio%=0.6×MSTP+60). Even though the PI ratio of the cases was superior to this threshold of tolerance for parent artery occlusion, complementary low flow bypass was added in the acute case for the overwhelming succeeding vasospasm and for securing the flow to peripheral perforators, which resulted in a successful treatment without any ischemic events.

Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer) to the Brain, Diagnosed at 18 Weeks' Gestation: A Case Report and Review of the Literature.

We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC). A 35-year-old woman (gravida 2, para 0-1-0-1) underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]). The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks' gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks' gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome.

We report a case of rectal cancer with microsatellite instability (MSI) that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1) without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient's family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer.

An Unusual Case of Fulminant Type 1 Diabetes during the Second Trimester of Pregnancy.

Fulminant type 1 diabetes is a new subtype of rapid-onset type 1 diabetes, with pancreatic exocrine dysfunction, that usually develops during the third trimester of pregnancy. We describe a patient with fulminant type 1 diabetes onset during her second trimester, resulting in premature delivery. The 34-year-old woman, without any known risk factors for diabetes mellitus, experienced a sudden stillbirth at 24-weeks gestation. Her blood glucose level was 950 mg/dL and she was positive for urine ketone bodies. The condition met all the diagnostic criteria for fulminant type 1 diabetes, and was diagnosed as such. Although this disease is rare, its progression is rapid, and its clinical course is severe and occasionally leads to death; therefore, a full knowledge of the disease is important to facilitate an accurate diagnosis.

Methamphetamine- and 3,4-methylenedioxymethamphetamine-induced behavioral changes in histamine H3-receptor knockout mice.

Histamine H(3) receptors inhibit the release of not only histamine itself, but also other neurotransmitters including dopamine. Previous papers have reported that histaminergic neurons inhibit psychostimulant-induced behavioral changes. To examine whether deficiency in histamine H(3) receptors influences psychostimulant-induced behavioral sensitization and reward, we examined locomotor activity, conditioned place preference (CPP), and c-Fos expression in histamine H(3) receptor-gene knockout mice (H3KO) and their wild-type (WT) counterparts before and after treatment with methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA). The increase in locomotion induced by treatment with METH or MDMA was lower in histamine H3KO mice than in WT mice, while the locomotor sensitization was developed by METH or MDMA in both strains. However, no significant difference in METH- and MDMA-induced preference scores of CPP between histamine H3KO mice and WT mice was observed. Following treatment with METH, the number of c-Fos-positive neurons in the the caudate-putamen of histamine H3KO mice was lower than that in the caudate-putamen of WT mice. In contrast, there was no significant difference in the number of the psychostimulant-induced c-Fos-positive cells in the nucleus accumbens between the two strains of mice. These findings suggest that deficiency in histamine H(3) receptors may have inhibitory effects on psychostimulant-induced increase in locomotion, but insignificant effects on the reward.

Blocking histamine H(1) improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection.

The aim of this study was to investigate the effects of histamine H(1) and H(3) antagonists on learning and mnemonic dysfunction in mice. Two H(1) antagonists, pyrilamine and clozapine, and the prototypic H(3) antagonist thioperamide were used to study the role of histamine in mice with social isolation and repeated methamphetamine administration. Mice with social isolation and repeated methamphetamine administration showed significant disruption of prepulse inhibition as compared to both the socially-housed mice and isolation-housing mice. Furthermore, social isolation and repeated methamphetamine administration caused significant learning and mnemonic dysfunctions. Treatment with clozapine improved learning and mnemonic ability in all of the tasks. Pyrilamine treatment ameliorated performance in all the tests examined except for the passive avoidance test. Thioperamide, however, did not change the learning and mnemonic ability. Donepezil, an acetylcholinesterase inhibitor, reversed the learning and mnemonic dysfunction in all four tasks. The present study has shown that blockade of histamine H(1) receptor improved the learning and mnemonic ability in mice, raising the possibility that treatment with clozapine or pyrilamine may improve learning and mnemonic performance in certain patients with psychiatric diseases such as schizophrenic patients with cognitive dysfunction.

The monocyte chemotactic protein-1 gene may contribute to hypertension in Dahl salt-sensitive rats.

In a previous study, we performed a genome-wide quantitative trait loci (QTLs) analysis for blood pressure using F2 rats derived from Dahl salt-sensitive (DS) and Lewis (LEW) rats and identified two QTLs that influenced blood pressure levels. Although we determined that one of the causative genes in the chromosome (Ch) 1 region seemed to be Klk1, we did not perform detailed analyses on the Ch10 QTL region. The purpose of the present study was to identify candidate genes that influence blood pressure in the Ch10 QTL region. Using microarray analysis, we compiled a list of the genes that are differentially expressed between the two strains and that were localized to the Ch10 QTL region. Subsequent reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis identified that, while the expression levels of Ccl2 mRNA were not different between the kidneys of DS and LEW rats fed a normal diet, those in DS were 10-fold higher than those in LEW under a high-salt diet. Although the promoter reporter assay failed to identify causative nucleotide changes that led to the differential expression, monocyte chemotactic protein-1 (MCP-1) release from isolated monocytes were significantly higher in DS than in LEW. Intriguingly, this Ch10 QTL for blood pressure was also a possible QTL for urinary albumin excretion. Since Ccl2 is well known to be involved in various types of renal injury, it is likely that a higher expression of Ccl2 might aggravate macrophage infiltration, which in turn could aggravate tubulointerstitial injury, and thereby accelerate salt-sensitive hypertension. Thus, Ccl2 appears to be a interesting candidate gene for salt-sensitive hypertension in DS.

Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration.

Hepatoma-derived growth factor (HDGF) is a nuclear protein homologous to the high-mobility group B1 family of proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF was increased in spinal motor neurons of a mouse model of motor neuron degeneration, polyglutamine-tract-binding protein-1 (PQBP-1) transgenic mice, before onset of degeneration. HDGF promoted neurite extension and survival of spinal motor neurons in primary culture. HDGF repressed cell death of motor neurons after facial nerve section in newborn rats in vivo. We also found a significant increase in p53 in spinal motor neurons of the transgenic mice. p53 bound to a sequence in the upstream of the HDGF gene in a gel mobility shift assay, and promoted gene expression through the cis-element in chloramphenicol acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in CSF of PQBP-1 transgenic mice. Collectively, our results show that HDGF is a novel trophic factor for motor neurons and suggest that it might play a protective role against motor neuron degeneration in PQBP-1 transgenic mice.

Effects of histamine H(3) antagonists and donepezil on learning and mnemonic deficits induced by pentylenetetrazol kindling in weanling mice.

Childhood epilepsy is one of the main risk factors for a variety of problems involving cognition and behavior. Pentylenetetrazol (PTZ) kindling is currently an acceptable model for epilepsy research. The objectives of this study are to clarify the learning and mnemonic characteristics of PTZ kindling in developing mice, and to examine the effects of thioperamide and JNJ-5207852, two histamine H(3) receptor antagonists and donepezil, an acetylcholinesterase (AChE) inhibitor, on learning and memory deficits induced by PTZ kindling in the brains of developing mice. PTZ kindling led to learning and mnemonic deficits as assessed by social discrimination, acoustic fear conditioning, water maze and passive avoidance tests. Thioperamide and JNJ-5207852, ameliorated PTZ kindling-induced learning and mnemonic deficits in all tests except for the water maze test. In addition, the learning and mnemonic impairments induced by PTZ kindling were significantly improved by donepezil in all tests. These findings suggest that histamine and acetylcholine are involved in the different processes of learning and memory in the brain and that histamine H(3) receptor antagonists might be useful in the treatment of cognitive impairment in epilepsy.