Brainstem Research Articles

Alterations of the amplitude of low-frequency fluctuation induced by repetitive transcranial magnetic stimulation combined with antidepressants treatment for major depressive disorder

We investigated the neuroimaging changes and clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants in major depressive disorder (MDD) patients. We scanned 35 patients with MDD and 27 healthy controls (HC) with resting-state functional magnetic resonance imaging (fMRI) before and after treatment. We analyzed amplitude of low-frequency fluctuation (ALFF) and the correlation with clinical variables. The rate of significant efficacy after treatment was higher in the combination treatment group than in the antidepressant group, although not statistically significant. At baseline, ALFF increased in the left middle temporal, brain stem, and left cerebellum and decreased in the right anterior cingulate (ACC), right orbital frontal cortex (OFC), and right caudate. ALFF increased in the left fusiform and decreased in the right lingual gyrus, left middle occipital gyrus, and left superior occipital gyrus after antidepressants. ALFF increased in the right ACC, right OFC, and right rectus after combination treatment. ALFF changes in the right ACC/OFC were negatively correlated with HAMD changes. After treatment, abnormal activity in some brain regions normalized, but these regions differed between the two treatment groups. rTMS combined with antidepressants therapy may improve MDD symptoms by improving neuronal activity levels in the right ACC and right OFC.

Analysis of the course and treatment of COVID-19: the experience of the Morozov Children’s City Clinical Hospital

Morozov Children’s City Clinical Hospital, almost in the first months of the development of the COVID-19 epidemic, began to admit not only patients with acute infection, but mainly with combined comorbid pathology. Based on a retrospective analysis of 290 medical records of children hospitalized with COVID-19 at the Children’s City Clinical Hospital, an analysis of children admitted to the hospital with predominantly comorbid pathology was carried out between April 2020 and September 2020. Six of these children had a fatal outcome. Most children were in the first 3 years of life (38,4 %) and puberty (37,3 %). The diagnoses of hospitalized patients were varied: pneumonia — 41 (14,4 %), surgical pathology and trauma — 69 (24,3 %), somatic pathology — 120 (42,3 %), including: diseases of the gastrointestinal tract, kidneys and urinary tract pathways, hematological diseases, neurological, type I diabetes mellitus, joint diseases, diseases of the newborn period, oncological diseases, diseases of the cardiovascular system. To diagnose covid pneumonia, along with rapid methods of SARS-COV2, computed tomography of the lungs was used. Analyzing the course of diseases in surgical children, it can be noted that coronavirus infection did not affect the course of the underlying disease. At the same time, COVID-19 infection in hematological patients provoked a worsening of the condition with symptoms of an acute respiratory viral infection (hyperthermia, weakness, cough, rhinitis). In patients with symptomatic focal epilepsy and in patients with increased intracranial pressure, SARS-COV-2 caused activation of seizures. It should be noted that the onset of type 1 diabetes was observed in 5 out of 6 admitted children. In these cases, COVID-19 infection was a provoking factor; it also caused an exacerbation in 1 child who had “long-term” diabetes. The article presents case histories and diagnoses of 6 children aged 3 years 9 months to 17 years with deaths, severe comorbid pathology (leukemia, brain stem tumor, immunodeficiency state), in whom COVID-19 infection aggravated the course of the underlying disease with the development of generalized combined bacterial infection, sepsis, bleeding.

Peripheral and central neurobiological effects of botulinum toxin A (BoNT/A) in neuropathic pain: a systematic review.

Botulinum toxin (BoNT), a presynaptic inhibitor of acetylcholine (Ach) release at the neuromuscular junction (NMJ), is a successful and safe drug for the treatment of several neurological disorders. However, a wide and recent literature review has demonstrated that BoNT exerts its effects not only at the "periphery" but also within the central nervous system (CNS). Studies from animal models, in fact, have shown a retrograde transport to the CNS, thus modulating synaptic function. The increasing number of articles reporting efficacy of BoNT on chronic neuropathic pain (CNP), a complex disease of the CNS, demonstrates that the central mechanisms of BoNT are far from being completely elucidated. In this new light, BoNT might interfere with the activity of spinal, brain stem, and cortical circuitry, modulating excitability and the functional organization of CNS in healthy conditions. Botulinum toxins efficacy on CNP is the result of a wide and complex action on many and diverse mechanisms at the basis of the maladaptive plasticity, the core of the pathogenesis of CNP. This systematic review aims to discuss in detail the BoNT's mechanisms and effects on peripheral and central neuroplasticity, at the basis for the clinical efficacy in CNP syndromes.

Image-guided biopsy of intracranial lesions in children, with a small robotic device: a case series.

Robot-assisted biopsies have gained popularity in the last years. Most robotic procedures are performed with a floor-based robotic arm. Recently, Medtronic Stealth Autoguide, a miniaturized robotic arm that work together with an optical neuronavigation system, was launched. Its application in pediatric cases is relatively unexplored. In this study, we retrospectively report our experience using the Stealth Autoguide, for frameless stereotactic biopsies in pediatric patients. Pediatric patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to May 2023 were included in this study. Clinical, neuroradiological, surgical, and histological data were collected and analyzed. Nineteen patients underwent 20 procedures (mean age was 9-year-old, range 1-17). In four patients, biopsy was part of a more complex surgical procedure (laser interstitial thermal therapy - LITT). The most common indication was diffuse intrinsic brain stem tumor, followed by diffuse supratentorial tumor. Nine procedures were performed in prone position, eight in supine position, and three in lateral position. Facial surface registration was adopted in six procedures, skull-fixed fiducials in 14. The biopsy diagnostic tissue acquisition rate was 100% in the patients who underwent only biopsy, while in the biopsy/LITT group, one case was not diagnostic. No patients developed clinically relevant postoperative complications. The Stealth Autoguide system has proven to be safe, diagnostic, and highly accurate in performing stereotactic biopsies for both supratentorial and infratentorial lesions in the pediatric population.

Evaluation of cochlear and auditory brainstem functions in COVID-19 patients; a case control study

BackgroundMany viral infections can cause hearing loss due to affection of cochlear hair cells or neurogenic pathway. Although, the damage secondary to viral infections is mainly cochlear affection; auditory brainstem can be affected as well. It was predicted that SARS-COV-2 infection can similarly affect the auditory system. This study aimed to detect affection in auditory system and if present investigate the possible site of lesion (up to the level of the brain stem) in relation to COVID-19 infection.MethodsThis is a case control study, where the study group constituted of thirty adults, diagnosed with COVID-19 at least 2 weeks prior to testing and up to 6 months, without previous auditory complaints pre-COVID-19 or other risk factors that could affect the auditory pathway. Fifteen adult participants that were age and gender matched to the study group with no previous history of covid-19 infection constituted the control group. Audiological evaluations done to all participants were pure-tone and speech audiometry, tympanometry, transient-evoked otoacoustic emission with and without contralateral suppression and auditory brainstem response measurements.ResultsThe study group showed significantly worse pure tone thresholds at high frequencies 4 and 8 kHz (p < 0.01), significantly worse transient-evoked otoacoustic emission signal to noise ratio at 2800 Hz and 4000 Hz (p < 0.05) and significantly lower total suppression index (p<0.05). On the other hand, there was no significant difference between both groups in auditory brainstem response wave latencies (p > 0.05).ConclusionCOVID-19 had subtle effect on cochlear basal turn, and it is shown that the auditory efferent system may also be affected, while the auditory nerve and afferent brainstem pathways seems to be spared. Moreover, the absence of the symptoms of auditory dysfunction postcovid-19 does not guarantee normal auditory functions.

Invertebrate genetic models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by the progressive death of motor neurons in the cerebral cortex, brain stem, and spinal cord. The exact mechanisms underlying the pathogenesis of ALS remain unclear. The current consensus regarding the pathogenesis of ALS suggests that the interaction between genetic susceptibility and harmful environmental factors is a promising cause of ALS onset. The investigation of putative harmful environmental factors has been the subject of several ongoing studies, but the use of transgenic animal models to study ALS has provided valuable information on the onset of ALS. Here, we review the current common invertebrate genetic models used to study the pathology, pathophysiology, and pathogenesis of ALS. The considerations of the usage, advantages, disadvantages, costs, and availability of each invertebrate model will also be discussed.

Influence of Brainstem's Area A5 on Sympathetic Outflow and Cardiorespiratory Dynamics.

Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.

Gender-related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model.

Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor-associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.

Education On Handling Choking On Babies And Children In Dusun 1 Kismoyoso Village

Choking is a very dangerous emergency, because in a few minutes there will be a general or complete lack of oxygen so that in just minutes the client will lose reflexes, heart rate and death permanently from the brain stem. The method carried out is socialization regarding the handling of choking on infants and children in Hamlet 1, Kismoyoso Village, Ngemplak District, Boyolali Regency, Central Java which was carried out on Saturday, August 5, 2023. This socialization is in the form of material presentation and gives examples of what techniques can be used if the baby/child chokes. The purpose of socializing the handling of choking babies is to prevent the occurrence of significant negative impacts on infants and children caused by choking. With this socialization, it is hoped that parents can provide first aid with several techniques.&#x0D; Keywords: signs, factors, prevention and treatment of choking in infants&#x0D;

Study on location of cerebral lesion among patients with hemorrhagic cerebrovascular accident

Background: In hemorrhagic cerebrovascular accident, bleeding occurs directly into the brain parenchyma. Intracerebral hemorrhage usually occurs at certain sites in the brain, i.e., thalamus, putamen, cerebellum, and brain stem. The surrounding area of brain may be damaged by pressure produced by the mass effect of the hematoma. Increase in intracranial pressure occurs. Aims and Objectives: The aim and objective of the study are to compare the localization of cerebral lesions with the frequency of intraventricular hemorrhage and to study the prognosis of hemorrhagic cerebrovascular accident (CVA) as per its anatomical location in computed tomography (CT) scan. Materials and Methods: One-year observational cross-sectional study was conducted in 60 patients with CT scan diagnosed hemorrhagic CVA. Results: Regarding the site of the hemorrhagic CVA, the most commonly affected area was basal ganglia (46.7%) followed by thalamus (18.3%); other areas include pons (8.3%), paraventricular (8.3%), cerebellar (6.7%), lobar (5%), internal capsule (3.3%), and intraventricular (3.3%). Conclusion: This study reflects a spectrum of cerebral location of hemorrhagic stroke which may help in the management of hemorrhagic CVA patients.

Infragalenic triangle as a gateway to dorsal midbrain and posteromedial thalamic lesions: descriptive and quantitative analysis of microsurgical anatomy.

Anatomical triangles provide neurosurgeons with the specificity required to access deep targets, supplementing more general instructions, such as craniotomy and approach. The infragalenic triangle (IGT), bordered by the basal vein of Rosenthal (BVR), precentral cerebellar vein (PCV), and the quadrangular lobule of the cerebellum, is one of a system of anatomical triangles recently introduced to guide dissection to brainstem cavernous malformations and has not been described in detail. This study aimed to quantitatively analyze the anatomical parameters of the IGT and present key nuances for its microsurgical use. A midline supracerebellar infratentorial (SCIT) approach through a torcular craniotomy was performed on 5 cadaveric heads, and the IGT was identified in each specimen bilaterally. Anatomical measurements were obtained with point coordinates collected using neuronavigation. Three cadaveric brains were used to illustrate relevant brainstem anatomy, and 3D virtual modeling was used to simulate various perspectives of the IGT through different approach angles. In addition, 2 illustrative surgical cases are presented. The longest edge of the IGT was the lateral edge formed by the BVR (mean ± SD length 19.1 ± 2.3 mm), and the shortest edge was the medial edge formed by the PCV (13.9 ± 3.6 mm). The mean surface area of the IGT was 110 ± 34.2 mm2 in the standard exposure. Full expansion of all 3 edges (arachnoid dissection, mobilization, and retraction) resulted in a mean area of 226.0 ± 48.8 mm2 and a 2.5-times increase in surface area exposure of deep structures (e.g., brainstem and thalamus). Thus, almost the entire tectal plate and its relevant safe entry zones can be exposed through an expanded unilateral IGT except for the contralateral inferior colliculus, access to which is usually hindered by PCV tributaries. Exposure of bilateral IGTs may be required to resect larger midline lesions to increase surgical maneuverability or to access the contralateral pulvinar. The IGT provides a safe access route to the dorsal midbrain and reliable intraoperative guidance in the deep and complex anatomy of the posterior tentorial incisura. Its potential for expansion makes it a versatile anatomical corridor not only for intrinsic brainstem lesions but also for tumors and vascular malformations of the pineal region, dorsal midbrain, and posteromedial thalamus.

Characteristics of Visual Contrast Sensitivity and Ocular Microtremor in Schizophrenia

Background: schizophrenia is a severe mental illness characterized not only by cognitive but also sensory impairments, including the visual system. Research suggests impairments in contrast processing in schizophrenia, but evidence regarding the nature of these impairments is inconsistent. The theory of tremor modulation signal connects contrast sensitivity with the parameters of ocular microtremor – high-frequency and low-amplitude micromovements that are controlled by neurons of the nuclei of the brain stem. The parameters of ocular microtremor in psychopathology, in particular in schizophrenia, have not been described in the scientific literature.The aim of the study was to study the characteristics of contrast sensitivity and microtremor of the eyes of patients with schizophrenia.Patients and methods: to register contrast sensitivity, the method of computer visocontrastometry was used. Gabor elements were presented with spatial frequencies of 0.4, 1.0, 3.0, and 10 cycles/deg. Eye microtremor was recorded using a non-contact high-speed video recording method using an original optical system. The study involved 30 patients diagnosed as paranoid schizophrenia and 30 people without psychopathology and neurological diseases.Results: the contrast sensitivity of patients was reduced in the region of medium and high spatial frequencies compared with conditionally healthy controls, which may be associated with the chronic course of the disease. Ocular microtremor in the patient group was characterized by a lower frequency and a higher amplitude compared to the control group.Conclusions: contrast sensitivity and ocular microtremor are considered as potential markers for determining the functional state in schizophrenia, which requires further research and accumulation of experimental data.

CNS DEPRESSANT ACTIVITY OF KASHAYA OF ASOKA – SARACA ASOCA ROXB. DE (WILDE.)

Ayurveda explains chikitsa (treatment – mode to attain health) as a conglomeration of chatushpada’s (four limbs). Pharmacological categorization of drugs can be explored for the first time from the Charaka Samhita, Shadvirechana Shatasriteeya Adhyaya. Asoka - Saraca asoca [Roxb] de Wilde has been included in the Vedanasthapana mahakashaya (group of drugs which alleviates a specific sensation) mentioned by Acharya Charaka, which is explained as streenam uchrokanashanaya by the Nighantukaara’s. The etymology of soka is chittavikalatha, which is a ‘lead’ to the action of a drug on “manasika bhava’s”. In clinical experience, apart from the pain, associated symptoms like nausea, vomiting, delirium, insomnia, emotional instability, nervousness, irritability, anger, and fear are also relieved by its usage. Till now, the pharmacological action of Asoka on “manasika bhava’s” remains unexplored. Hence, a preliminary experimental study has been undertaken on the reverse pharmacological aspect to assess the action of this drug on CNS. The depressant action of drugs on CNS is mediated through both neural and hormonal mechanisms. The immediate reduction in spontaneous motor activity was achieved through the neural mechanism, and the prolonged effect was achieved through the hormonal action. The drug possesses bitter principles. The functional bitter taste is expressed in brain cells by bitter taste receptors T2R’s. T2R-4, T2R-107, and T2R-38 transcripts are found in the brain stem, cerebral cortex and cerebellum. The drug is a potent source of phytoestrogen, which has oestrogen-mimicking action. The drug significantly reduces spontaneous motor activity in the CNS depressant activity study on all assessment days, with a p-value.

Blink reflex changes in patient with long COVID headache

Background: Headache is a common symptom of long COVID. Blink Reflex (BR) may indicate possible brainstem dysfunction or changes in excitability in the headache. In this study, we aimed to reveal whether one of the underlying mechanisms of headache in long COVID is dysfunction in the nociceptive centers in the brainstem. Methods: The study included 29 individuals with confirmed 2019 coronavirus disease (COVID-19) and 17 healthy volunteers. Individuals were divided into 3 groups: post-COVID-19 headache (Group 1), post-COVID-19 headache-free (Group 2) and healthy individuals (Group 3). Individuals in the groups were subjected to BR and the parameters obtained with BR were compared between the 3 groups. Results: Accordingly, when Group 1 and Group 2 were compared, the mean latency of the R1 component of the BR and the mean latency of the ipsilateral R2 component obtained via right-sided electrical stimulation were found to be longer in Group 1. When Group 1 and Group 3 were compared, the latency differences of the ipsilateral R2 component and contralateral R2 component of the BRs were found to be longer in Group 3, indicating distinct patterns of neural response between the two groups. Conclusion: In long COVID patients experiencing headache symptoms, the underlying cause of the pain symptom may be brain stem dysfunction.

Clinical significance and prognostic value of serum autoantibody tests in multiple sclerosis.

It is known that multiple sclerosis (MS) often coexists with other autoimmune diseases. Hence, autoantibody (auto-Ab) tests may prove useful in the differential diagnosis of MS. The objectives of this study were to: (a) investigate the prevalence of auto-Ab positivity at the beginning of the MS diagnostic process; (b) assess whether Auto-Ab+ and Auto-Ab- patients differ in baseline clinical, laboratory, and radiological parameters; and (c) investigate the prognostic value during a two-year follow-up period. This retrospective study consisted of 450 patients aged between 18 and 55 years. All patients underwent a wide range of auto-Ab tests, anti-nuclear antibody (ANA) tests in particular. The expanded disability status scale (EDSS) scores of the patients were recorded at the time of diagnosis and at the end of a two-year follow-up period. The mean age of the 212 patients, 148 (69.8%) female and 64 (30.2%) male, included in the study sample was 37 ± 10.83 years. The rate of relapsing cases was 84% (178). Oligoclonal band (OCB) was positive in 142 (86.6%) of the 164 tested cases. At least one of the auto-Ab tests was positive in 51 (24.1%) of the cases. ANA test was positive in 21 (9.9%) cases. There was no significant difference between patients with at least one positive auto-Ab test and without any positive auto-Ab test and between ANA-positive and ANA-negative patients in terms of age, gender, clinical features of MS, presence of brain stem lesion, presence of spinal lesion, OCB positivity, level of clinical improvement after the first pulse steroid treatment, family history, presence of comorbidity, presence of autoimmune disease, or EDSS scores recorded at the end of the two-year follow-up period (p > 0.05). Our study findings revealed that Auto-Ab positivity was more common in MS patients than in the general population. However, given their limited contribution to the diagnosis and differential diagnosis of MS with no effect on the prognostic process, auto-Ab tests should be requested only in the event of accompanying autoimmune disease symptoms, and in cases where the diagnosis of MS may be suspected.

Structural MRI of the Brain in Treatment-Resistant Schizophrenia

Background: despite a significant progress of psychopharmacology, treatment-resistant schizophrenia (TRS) remains a challenge for clinicians. The etiology and pathogenesis of TRS probably differ from schizophrenia susceptible to therapy, which underlies the non-respondence to most antipsychotics.Objective: to establish morphometric gray matter brain structural features in TRS as well as to analyze the association of these parameters with the clinical characteristics of patients.Patients and methods: 21 right-handed male patients diagnosed with paranoid schizophrenia and meeting criteria for treatment resistance and 21 matched healthy controls underwent MRI and clinical examination. T1-weighted images were processed via FreeSurfer 7.1.1. For each subject average values for the cortex thickness and area, volumes of subcortical structures, brain stem structures, and separately volumes of the amygdala nuclei and hippocampal subregions were obtained. Intergroup comparisons and correlations with clinical scales (PANSS, CDSS) and antipsychotic dosage in chlorpromazine equivalent were calculated. Results: TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions, volumes of the amygdala, hippocampus and nucleus accumbens, as well as a number of amygdala nuclei and hippocampal subregions bilaterally. The volume of the right globus pallidus, on the contrary, was increased.Conclusion: the widespread gray matter thinning in TRS confirmed the other researchs, which described resistance as a more severe form of schizophrenia that affects brain structures worse. The increase of globus pallidus volume is a surprising result, which is not yet clearly explained.

Curative effect analysis of robot-assisted drainage surgery in treatment of spontaneous hypertensive brainstem hemorrhage.

Spontaneous hypertensive brainstem hemorrhage (HBSH) is characterized by sudden onset, rapid progression and poor prognosis. There has been a growing tendency of surgical treatment for HBSH. This study aimed to investigate outcomes and potential factors associated with the prognosis of robot-assisted drainage surgery for HBSH treatment. Patients with HBSH from July 2016 to March 2023 at a single neurosurgery center were included and divided into conservative group and surgical groups. Baseline and clinical data, radiographic characteristics, complications, and outcome evaluations were recorded and analyzed. A total of 125 patients, with 74 in the conservative group and 51 in the surgical group, were enrolled in the study. Mortality at 6 months was 59/74 (79.7%) in the conservative group and 9/51 (17.6%) in the surgical group. Twenty-four patients (47.1%) achieved favorable outcomes in the surgical group, whereas this rate in the conservative group was only 5.4% (4/74). There was a significant difference in NIHSS, GCS, and mRS at 6 months between surviving patients in the conservative and surgical groups. In prognostic analysis in the surgical subgroup, initial GCS score [5 (IQR 4-7) vs. 3 (IQR 3-4), p < 0.001], NIHSS [36 (IQR 32-38) vs. 40 (IQR 38-40), p < 0.001], smoking history [45.8% (11/24) vs. 74.1% (20/27), p = 0.039], hematoma volume [6.9 (IQR 6.2-7.6) vs. 9.6 (IQR 7.3-11.4), p = 0.001], and hemorrhage location (p = 0.001) were potential risk factors for poor 6-month prognosis after robot-assisted surgery for HBSH. Based on the results of this study, robot-assisted minimally invasive drainage of brain stem hematoma may significantly reduce mortality and improve prognosis. Surgery should be conducted for selected patients.

LRRC25 expression during physiological aging and in mouse models of Alzheimer's disease and iPSC-derived neurons.

The leucine-rich repeat-containing protein 25 (LRRC25) is relatively a novel protein with no information on its role in neuronal or brain function. A recent study suggested LRRC25 is a potential risk factor for Alzheimer's disease (AD). As a first step to understanding LRRC25's role in the brain and AD, we found LRRC25 is expressed in both cell membranes and cytoplasm in a punctuate appearance in astrocytes, microglia, and neurons in cell lines as well as mouse brain. We also found that LRRC25 expression is both age- and brain region-dependent and that 1-day-old (1D) pups expressed the least amount of LRRC25 protein compared to adult ages. In the APΔE9 mice, immunoblot quantified LRRC25 protein levels were increased by 166% (**p < 0.01) in the cortex (CX) and by 215% (***p < 0.001) in the hippocampus (HP) relative to wild-type (WT) controls. Both the brainstem (BS) and cerebellum (CB) showed no significant alterations. In the 3xTg mice, only CX showed an increase of LRRC25 protein by 91% (*p < 0.05) when compared to WT controls although the increased trend was noted in the other brain regions. In the AD patient brains also LRRC25 protein levels were increased by 153% (***p < 0.001) when compared to normal control (NC) subjects. Finally, LRRC25 expression in the iPSC-derived neurons quantified by immunofluorescence was increased by 181% (**p < 0.01) in AD-derived neurons when compared to NC-derived neurons. Thus increased LRRC25 protein in multiple models of AD suggests that LRRC25 may play a pathogenic role in either Aβ or tau pathology in AD. The mechanism for the increased levels of LRRC25 in AD is unknown at present, but a previous study showed that LRRC25 levels also increase during neonatal hypoxic-ischemia neuronal damage. Based on the evidence that autophagy is highly dysregulated in AD, the increased LRRC25 levels may be due to decreased autophagic degradation of LRRC25. Increased LRRC25 in turn may regulate the stability or activity of key enzymes involved in either Aβ or hyperphosphorylated tau generation and thus may contribute to increased plaques and neurofibrillary tangles.

Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.

Clinical relevance of reversible cerebral vasoconstriction syndrome in pregnant women with posterior reversible encephalopathy syndrome: review of case reports in Japan.

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.