Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus.

Neuroprotective therapeutic potential for restoring dysregulated microRNA (miRNA) expression has previously been demonstrated in a gerbil cerebral infarction model. However, since temporal changes in miRNA expression profiles following stroke onset are unknown, miRNAs proving to be useful therapeutic targets have yet to be identified. We evaluated cognitive function, hippocampal neuronal cell death, and microarray-based miRNA expression profiles at 5, 9, 18, 36, and 72 h after 5-min whole brain ischemia in gerbils. A decline in cognitive function occurred in parallel with increased neuronal cell death 36-72 h after ischemia. The Jonckheere-Terpstra test was used to analyze miRNA expression trends 5-72 h after ischemia. The expression levels of 63 miRNAs were significantly upregulated, whereas 32 miRNAs were significantly downregulated, monotonically. Of the 32 monotonically downregulated miRNAs, 18 showed the largest decrease in expression 5-9 h after ischemia. A subset of these dysregulated miRNAs (miR-378a-5p, miR-204-5p, miR-34c-5p, miR-211-5p, miR-34b-3p, and miR-199b-3p) could be associated with brain ischemia and neuropsychiatric disorders.

18F-THK5351 Positron Emission Tomography Clearly Depicted Progressive Multifocal Leukoencephalopathy After Mantle Cell Lymphoma Treatment.

An 84-year-old Japanese woman presented with left hemiplegia 8 months after completing chemotherapy for mantle cell lymphoma. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion extending from the right parietal lobe to the left parietal lobe. Compared with these MRI results, 18F-THK5351 PET revealed more extensive accumulation. A brain biopsy showed progressive multifocal leukoencephalopathy (PML). Immunohistochemistry and John Cunningham virus (JCV) DNA-polymerase chain reaction indicated JCV infection. Therefore, a diagnosis of PML was made. 18F-THK5351 PET, indicative of activated astrocytes, clearly depicted PML lesions composed of reactive and atypical astrocytes. 18F-THK5351 PET may capture fresh progressive PML lesions better than MRI.

Cytotoxic Lesions of the Corpus Callosum (CLOCC) Suggesting Exacerbation by Heterogeneous COVID-19 Booster Vaccination.

Cytotoxic lesions of the corpus callosum (CLOCC) is a disease entity associated with reversible lesions of the corpus callosum on magnetic resonance imaging (MRI). CLOCC is caused by a variety of etiologies, but CLOCC after vaccination is extremely rare. Four prior cases of CLOCC after the first dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have been reported; these were localized to the splenium and showed early clinical and neuroradiological recovery. We experienced an unusual case in which a heterogeneous COVID-19 booster vaccination caused rather severe CLOCC damage. A 74-year-old Japanese woman presented with ataxia, high fever, and hearing loss several days after her third vaccination against COVID-19. This booster was an mRNA-1273 while her first and second vaccinations were both BNT162b2 type. SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was negative, but serum SARS-CoV-2 S-IgG antibodies were elevated. Her cerebrospinal fluid (CSF) showed an elevated cell count and high levels of protein and interleukin-6 (IL-6). Brain MRI showed CLOCC spreading throughout the body of the corpus callosum. After the exclusion of other potential causes, the diagnosis of vaccination-related CLOCC was made. Six months later, recovery of clinical and MRI findings remained incomplete. It was suggested that the patient's CLOCC might have been caused by the increase in CSF IL-6 due to an enhanced immune response from the heterogeneous vaccination, resulting in more severe damage to the corpus callosum than usual.

Age­related brainstem degeneration through microRNA modulation in mice.

Histopathological changes occur in the brainstem during the early stages of Alzheimer's disease (AD), with the pathological changes of the brain lesions ascending progressively in accordance with the Braak staging system. The senescence­accelerated mouse prone 8 (SAMP8) mouse model has been previously used as a model of age­dependent neurodegenerative diseases, including AD. In the present study, microRNAs (miRNAs) that were upregulated or downregulated in SAMP8 brainstems were identified using miRNA profiling of samples obtained from miRNA arrays. The preliminary stage of cognitive dysfunction was examined using male 5­month­old SAMP8 mice, with age­matched senescence­accelerated mouse resistant 1 mice as controls. A Y­maze alternation test was performed to assess short­term working memory and miRNA profiling was performed in each region of the dissected brain (brainstem, hippocampus and cerebral cortex). SAMP8 mice tended to be hyperactive, but short­term working memory was preserved. Two miRNAs were upregulated (miR­491­5p and miR­764­5p) and two were downregulated (miR­30e­3p and miR­323­3p) in SAMP8 brainstems. In SAMP8 mice, the expression level of upregulated miRNAs were the highest in the brainstem, wherein age­related brain degeneration occurs early. It was demonstrated that the order of specific miRNA expression levels corresponded to the progression order of age­related brain degeneration. Differentially expressed miRNAs regulate multiple processes, including neuronal cell death and neuron formation. Changes in miRNA expression may result in the induction of target proteins during the early stages of neurodegeneration in the brainstem. These findings suggest that studying altered miRNA expression may provide molecular evidence for early age­related neuropathological changes.

Significance of Cortical Ribboning as a Biomarker in the Prodromal Phase of Sporadic Creutzfeldt-Jakob Disease.

A 63-year-old woman who presented for orofacial dystonia showed cortical ribboning, a typical MRI finding in sporadic Creutzfeldt-Jakob disease (sCJD). However, real-time quaking-induced conversion (RT-QuIC), the most sensitive method for an early diagnosis of sCJD, was negative. She developed sCJD six months later, at which time RT-QuIC became positive. The cerebral blood flow showed a decrease in the cerebral cortex (especially in the supramarginal gyrus) consistent with cortical ribboning, but an increase in the basal ganglia, probably involved in orofacial dystonia. Cortical ribboning on MRI might be a better biomarker than RT-QuIC in the prodromal phase of sCJD.

A cerebrospinal fluid microRNA analysis: Progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68­82 years. A total of 8 age­ and sex­matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR­204­3p, miR­873­3p and miR­6840­5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin­proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome­wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies.

Gastrointestinal Residue Removal Using a Balloon Overtube under Ultrathin Endoscopic Navigation: Ex Vivo and In Vivo Experimental Studies.

Pooled gastric residues involving blood clots and food interrupt appropriate endoscopic intervention, leading to poor outcomes in endoscopic hemostasis and lifesaving. However, procedures and devices that enable the effective removal of gastrointestinal residues remain unsatisfactory. This study aimed to evaluate the efficacy and safety of our developed suction method in ex vivo and in vivo studies. We created a hand-made device with a large suction diameter, consisting of a balloon overtube and an ultrathin endoscope for navigation. In the ex vivo study, we compared the success rate and the suctioning time for four types of simulated residue between a standard endoscope and our device. Our device had s significantly higher suction ability and a shorter procedure time than the standard endoscope. The subsequent in vivo animal study involved five beagle dogs that were administered with food jelly to mimic gastric residue. Suction was performed twice for five dogs (ten attempts). The outcome measure was the successful procedure rate; secondary outcomes were procedure-associated complications and procedure time. The procedure was successful in all attempts, without any complications. The mean procedure time was 5 min. This novel method enabled the efficient and safe removal of gastric residue, and our findings will likely lead to the development of the instrument.

Ascending spinal tract formation in chick embryo originating from different spinal regions.

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

Premedication of hemin for eradication therapy of Helicobacter pylori in patients with porphyria.

Eradication therapy of Helicobacter pylori may be safe if hemin has been intravenously administered in advance, even in patients with a history of recurrent acute porphyria attack.

Rapid Eye Movement Sleep Behavior Disorder-like Symptoms Due to Arousal Responses Associated with Severe Obstructive Sleep Apnea-hypopnea.

A 78-year-old man suspected of having α-synucleinopathies received a high score on a validated questionnaire for rapid eye movement (REM) sleep behavior disorder (RBD). Although he did in fact have unpleasant dreams and vigorous behaviors, polysomnography (PSG) found only obstructive sleep apnea-hypopnea (OSAH). The RBD-like symptoms corresponded with arousal responses, namely augmented inspiratory effort and leg movements, to his frequent apnea-hypopnea events during REM sleep. Thus, severe OSAH might cause RBD-like symptoms. PSG can discriminate real RBD from RBD-like symptoms associated with severe OSAH and therefore may be essential for determining an appropriate course of treatment in certain patients.

Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus.

Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070-2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs.

Repeated anti-N-methyl-D-aspartate receptor encephalitis coexisting with anti-myelin oligodendrocyte glycoprotein antibody-associated diseases: A case report.

The coexistence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases has been reported. We report the case of a 36-year-old woman who presented with repeated typical anti-NMDAR encephalitis coexisting with unusual symptoms not consistent with anti-NMDAR encephalitis. Apart from the anti-NMDAR encephalitis, her first episode was characterized by balance disability with bilateral medial frontal cortical lesions, suggesting the involvement of the cortico-reticular projections and the basal ganglia-brainstem projections. The second episode presented with Broca's aphasia caused by involvement of the Broca's area and lower part of the precentral gyrus. The detection of MOG-Ab in both episodes suggested the coexistence of MOG-Ab-associated diseases. Thus, an evaluation of MOG-Ab should be considered when anti-NMDAR encephalitis presenting with atypical symptoms is encountered.