Central Lobule Research Articles

Posterior Interhemispheric-Transtentorial Approach for Resection of an Arteriovenous Malformation of the Superior Medullary Velum and Fourth Ventricle: 2-Dimensional Operative Video.

Brain arteriovenous malformations (AVMs) of the fourth ventricle represent a rare subtype associated with an aggressive natural course.1,2 In this case, a woman in her early 50s presented with dizziness. An AVM was diagnosed in the left superior cerebellar peduncle extending into the fourth ventricle. The AVM was supplied by superior cerebellar artery branches and classified as a Spetzler-Martin grade III and a Lawton-Young grade III, with a supplemented grade of 6.3,4 Being a single case report, institutional review board approval was not needed. Patient consent was obtained. The lesion was accessed through a torcular craniotomy and posterior interhemispheric-transtentorial approach, employing gravity to naturally retract the parietooccipital lobe.5-7 Dissection continued into the quadrigeminal and ambient cisterns, where the tentorium was incised parallelling the straight sinus to reach the superior vermis. Partial resection of the lingual and central lobules of the vermis facilitated access to the superior medullary velum. The superior cerebellar artery feeders were divided and followed to the superior cerebellar peduncle and through the superior medullary vellum. A vertical incision in the superior medullary velum facilitated entry into the fourth ventricle, where the AVM nidus was dissected circumferentially and resected en bloc. Intraoperative indocyanine green videoangiography and postoperative digital subtraction angiography confirmed complete obliteration of the AVM. After surgery, the patient experienced mild ataxia, but motor symptoms greatly improved during 3-month follow-up. This video illustrates resection of a complex fourth ventricular AVM through a posterior interhemispheric-transtentorial approach, highlighting pivotal considerations of patient positioning and approach selection to optimize treatment outcome for complex posterior fossa AVM resection.

Upper Lip Nodule as the First Manifestation of Sarcoidosis: A Case Report

Introduction: Sarcoidosis is a chronic disorder characterized by the presence of multiple granules, which could affect different systems and tissues. These granules are histologically characterized by non-caseous granulomatous inflammation; however, their etiology is still unknown. Previous reports state that different antigens may be involved. Sarcoidosis has been rarely reported in the Brazilian population. The objective of this study was to report a clinical case of sarcoidosis presenting with oral manifestations as the first sign and symptom. Case Presentation: An 85-year-old, nonsmoking, white woman was referred to the Department of Stomatology of our clinic in 2019, complaining of a persistently growing nodule on the upper lip and in the right arm subcutaneous tissue lasting for three months. Both lesions were painless and non-mobile/cohesive nodules with borrachoid consistency on palpation, well-delimited margins, and overlying normal-colored mucosa/skin. The oral nodule was surgically excised and sent for routine histopathological analysis, revealing granulomatous inflammation, the presence of central lobules of activated macrophages, epithelioid histiocytes, multinucleated Langerhans cells, and a peripheral cuff of mononuclear cells (lymphocytes). There was no evidence of central necrotic areas; however, asteroid bodies (i.e., starry inclusions) were rarely interspersed within multinucleated Langerhans cells. Warthin-Starry, Fite, and PAS special staining did not show any evidence of granulomatous pathogens, which was compatible with non-infectious granulomatosis. Complementary tests revealed hypercalcemia and elevated serum levels of alkaline phosphatase and angiotensin-converting enzyme. Conclusions: Sarcoidosis can manifest itself in several ways, so the diagnostic process needs to be thorough and comprehensive to confirm the disease. In addition, disease progression should be regularly monitored in patients.

Morphological examination of rat organs with T-2 toxicosis against the background of the use of the complex preventive agent "Zeapitox"

It is impossible to find out the true state of the tissue organization without conducting morphological studies. In this regard, histological analysis very objectively demonstrates the structure of cellular compositions, which is especially in demand when making a reliable diagnosis and monitoring therapeutic and preventive effectiveness. T-2 toxin, as a biogenic poison, poses a potentially permanent threat to human and animal health. It is also important that modern highly productive breeds of farm animals and bird crosses have an increased sensitivity to mycotoxins. In order to prevent mycotoxicosis, a selection of diets containing sorbents and adaptogens is promising in terms of economic and therapeutic effectiveness. The purpose of the experiment was to evaluate the preventive effectiveness of «Zeapitox» from a morphological point of view when rats were poisoned with T-2 toxin at the tissue level of a number of organs. The experiment involved 30 nonlinear rats, males weighing in the range of 190-210 grams. The first group served as biological control; individuals of the second group were given T-2 toxin at a dose of 1/10 of LD50; animals of the third group, in addition to T-2 toxin at a dose of 1/10 of LD50, were additionally fed at a dose of 0,5 % of the diet with the feed «Zeapitox». Under the influence of T-2 toxin on the histostructure of rat organ tissues, the following changes were registered: hyperemia, swelling, increased blood filling of blood vessels, as well as destructive processes of the central lobules of hepatocytes, intestinal epithelium and blood cells. The protective effect of the complex preventiveagent «Zeapitox» is manifested by normal blood filling in the spleen (red and white pulp), native beam structure of lobules and good visualization without pathological phenomena of hepatocytes, absence of edematous processes in the mucous membranes of intestinal.

Research on brain functions related to visual information processing and body coordination function of pilots based on the low-frequency amplitude method.

Research on the differences in physiological and psychological mechanisms of practitioners in different occupations is a current hot spot, such as pilots. This study explores the frequency-dependent changes of pilots' low-frequency amplitudes in the classical frequency band and sub-frequency band between pilots and general occupations. The goal of the current work is to provide objective brain images for the selection and evaluation of outstanding pilots. Twenty-six pilots and 23 age-, sex-, and education-matched healthy controls were included in this study. Then the mean low-frequency amplitude (mALFF) of the classical frequency band and sub-frequency band was calculated. The two-sample t-test was performed on SPM12 to analyze the differences between the flight group and control group in the classic frequency band. To explore the main effects and the inter-band effects of the mean low-frequency amplitude (mALFF), the mixed design analysis of variance was applied in the sub-frequency bands. Compared with the control group, left cuneiform lobe and the right cerebellum six area of pilots show significant difference in the classic frequency band. And the main effect results in the sub-frequency bands show that the area with higher mALFF in the flight group is located on the left middle occipital gyrus, the left cuneiform lobe, the right superior occipital gyrus, the right superior gyrus, and the left lateral central lobule. However, the area where the value of mALFF decreased is mainly located on the left rectangular cleft with surrounding cortex and the right dorsolateral superior frontal gyrus. Besides, compared with the slow-4 frequency band, the mALFF of the left middle orbital middle frontal gyrus of the slow-5 frequency band was increased, while the mALFF value of the left putamen, left fusiform gyrus, and right thalamus was decreased. The sensitivity of the slow-5 frequency band and the slow-4 frequency band to the pilots' different brain areas was also different. Also, the different brain areas in the classic frequency band and the sub-frequency band were significantly correlated with pilots' flight hours. Our findings showed that the left cuneiform brain area and the right cerebellum of pilots changed significantly during resting state. And there was a positive correlation between the mALFF value of those brain area and flight hours. The comparative analysis of sub-frequency bands found that the slow-5 band could elucidate a wider range of different brain regions, providing new ideas for exploring the brain mechanisms of pilots.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Longitudinal neuroplasticity after ankle sprain in mice: A voxel-based morphometry study on 11.7T MRI.

Lateral ankle sprains (LAS) might lead to joint sensory deafferentation, which induces maladaptive neuroplasticity, especially the morphological atrophy of the cerebellar vermis. However, longitudinal evidence on the causality of injury and neural differences is still lacking. To this end, this study aimed to determine whether the morphology of the central nervous system would be altered before and after ligament transection in LAS mouse models. A total of 40 C57BL/6 mice were randomly divided among the LAS, Sham and Blank groups. We repeatedly performed the balance beam test and neural voxel-based morphometry (VBM) measurements using an 11.7 T magnetic resonance imagingbefore and 2 months after the surgery. The results showed that for balance outcomes, the LAS group had a significantly longer time and more slips of the balance beam tests compared with the Sham and Blank groups at 2 months after surgery, with no significant difference among the three groups before surgery. Regarding the VBM analysis, the LAS group showed significantly lower VBM values in the central lobule IIIof the cerebellar vermis and medial amygdalar nucleus (MEA) compared with the Sham and Blank groups after surgery, with no significant difference among the three groups before surgery. In conclusion, lateral ligament injuries might lead to morphological atrophy of the cerebellar vermis in animal models, which might pave the way for the pathological process of ankle instability after LAS.

Surgical approaches to refractory central lobule epilepsy: a systematic review on the role of resection, ablation, and stimulation in the contemporary era.

Epilepsy originating from the central lobule (i.e., the primary sensorimotor cortex) is a challenging entity to treat given its involvement of eloquent cortex. The objective of this study was to review available evidence on treatment options for central lobule epilepsy. A comprehensive literature search (PubMed/Medline, EMBASE, and Scopus) was conducted for studies (1990 to date) investigating postoperative outcomes for central lobule epilepsy. The primary and secondary endpoints were seizure freedom at last follow-up and postoperative neurological deficit, respectively. The following procedures were included: open resection, multiple subpial transections (MSTs), laser and radiofrequency ablation, deep brain stimulation (DBS), responsive neurostimulation (RNS), and continuous subthreshold cortical stimulation (CSCS). A total of 52 studies and 504 patients were analyzed. Most evidence was based on open resection, yielding a total of 400 patients (24 studies), of whom 62% achieved seizure freedom at a mean follow-up of 48 months. A new or worsened motor deficit occurred in 44% (permanent in 19%). Forty-six patients underwent MSTs, of whom 16% achieved seizure freedom and 30% had a neurological deficit (permanent in 12%). There were 6 laser ablation cases (cavernomas in 50%) with seizure freedom in 4 patients and 1 patient with temporary motor deficit. There were 5 radiofrequency ablation cases, with 1 patient achieving seizure freedom, 2 patients each with Engel class III and IV outcomes, and 2 patients with motor deficit. The mean seizure frequency reduction at the last follow-up was 79% for RNS (28 patients), 90% for CSCS (15 patients), and 73% for DBS (4 patients). There were no cases of temporary or permanent neurological deficit in the CSCS or DBS group. This review highlights the safety and efficacy profile of resection, ablation, and stimulation for refractory central lobe epilepsy. Resection of localized regions of epilepsy onset zones results in good rates of seizure freedom (62%); however, nearly 20% of patients had permanent motor deficits. The authors hope that this review will be useful to providers and patients when tailoring decision-making for this intricate pathology.

362 Functional MRI to assess third trimester placental oxygenation

Higher R2* relaxation rates in functional magnetic resonance imaging (fMRI) reflect increased deoxygenated hemoglobin content and perhaps diminished oxygen exchange. We hypothesize that higher R2* relaxation rates may be found in women with obesity (OB) or diabetes (DM) as compared to normal weight women (NL). We aim to compare R2* relaxation rates in third trimester placentas of OB, DM and NL patients. We performed a prospective cohort pilot study using fMRI to evaluate placentas at 30-34 weeks gestation among patients with pre-pregnancy BMI ≥ 30 kg/m2 (OB), those with Type 1 or Type 2 DM diagnosed prior to pregnancy or in the first trimester (DM), and patients with pre-pregnancy BMI 18.5-24.9 kg/m2 without comorbidities (NL). HASTE T2 sequence was utilized to evaluate placental architecture and to select 1 cm2 regions of interest (ROI) within 3 centrally located lobules. ROI were selected at both the center and periphery of each lobule. Once ROI were identified via HASTE T2 images, the same ROI on the corresponding R2* maps were evaluated and relaxation rates were compared across groups. Primary outcome was mean R2* relaxation rates. Maternal demographic, clinical outcomes and relaxation rates were compared using ANOVA followed by Dunnett analysis. 5 OB, 3 DM, and 6 NL patients were included. Age, parity, race and ethnicity were similar across groups (Table 1). OB and DM had higher pre-pregnancy BMI (36.8±3.6 kg/m2 and 32.8±3=2.9 kg/m2, respectively) compared to NL (22.6±1.8 kg/m2, p < 0.001). Obstetric outcomes including gestational age at delivery and birthweight were similar (Table 1). Mean R2* relaxation rate was similar at the central portions of placental lobules across groups (Figure 1). Mean R2* relaxation rate at the peripheral portions of placental lobules was higher in OB (97.7±51.5, p = 0.003) and DM (66.3±39.4, p = 0.333) as compared to NL (52.3±32.0, Figure 1). R2* relaxation rates are higher at the periphery of central lobules in OB and DM patients compared to NL patients and may imply diminished placental oxygen exchange relative to NL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Analysis of cerebellum with magnetic resonance 3D T1 sequence in individuals with chronic subjective tinnitus.

Tinnitus is a symptom in which the patient can hear ringing, buzzing and similar sounds in the ear for 3months longer. In our study, we aimed to analyse the cerebellum volume and cerebellum connections in patients with chronic tinnitus using VolBrain program. A total number of 10 patients and 10 otherwise healthy peoples records were then enrolled. Volumetric analysis was performed with automated segmentation of the cerebellum and its lobules, using magnetic resonance imaging (MRI). The mean volumes of 10 cerebellar volume were compared between the tinnitus and control groups. Quadrangular lobular portion of the cerebellum, the flocculonodular part and the volume of the central cerebellar lobule were decreased in the tinnitus group. White and grey matter decreased and the amygdala size was increased. We found statistically important volumetric changes in our study. VolBrain can be used in the future for analysing, diagnosis and treatment tinnitus patients. We recommend to use this practical, free of charge and easy programme to analyse for tinnitus patients. This may provide us with practical and useful information about the disease. In patients with tinnitus, the volume loss was 17.48% in the quadrangular lobe, 21% in the central lobule, and 9.33% in the total cerebellum volume.

Beet root (Beta vulgaris) protects lipopolysaccharide and alcohol-induced liver damage in rat.

The purpose of this study was to investigate the protective effects of beet root (Beta vulgaris var. rubra) in lipopolysaccharide (LPS) and alcohol induced liver damage. Beta vulgaris ethanol extract (BVEE) showed good antioxidant activity in the contents of polyphenol and flavonoid compounds, and the electron-donating ability and ABTS+ radical scavenging activity. As for anti-inflammatory effect in RAW 264.7 cells, inhibition rate of nitric oxide production was increased in dose dependent manner. In hepatotoxicity model induced by LPS and alcohol in rat, BVEE significantly decreased serum AST, ALT and γ-GTP concentrations in a dose-dependent manner. The histopathological changes after H&E staining showed that fat accumulation and inflammatory cell infiltration were decreased by BVEE. The collagen fibers around the central lobule observed by Masson's trichrome staining were also decreased by BVEE. In addition, as for the immunohistochemical staining and Transmission electron microscopy, BVEE improved morphological characteristics of damaged liver lesion. The increased mRNA expressions of NF-κB, MAPK1, MAPK3, CYP2E1, and α-SMA were significantly decreased in BVEE treated group. These results indicated that BVEE would have protective effects in hepatotoxicity by altering various indicators related to the liver damage induced by LPS or alcohol.

Suppressor of fused controls cerebellum granule cell proliferation by suppressing Fgf8 and spatially regulating Gli proteins.

Cerebellar granule cell (GC) development relies on precise regulation of sonic hedgehog (Shh)-Gli signalling activity, failure of which is associated with motor disorders and medulloblastoma. Mutations in the pathway regulator suppressor of fused (Sufu), which modulates Gli activators and repressors, are linked to cerebellar dysfunction and tumourigenesis. The mechanism by which Sufu calibrates Shh signalling in GCs is unknown. Math1-Cre-mediated deletion of Sufu in mouse GC progenitors (GCPs) demonstrated that Sufu restricts GCP proliferation and promotes cell cycle exit, by promoting expression of Gli3R and suppressing Gli2 levels. Sufu is also required to promote a high threshold of pathway activity in GCPs. Remarkably, central cerebellar lobules are more deleteriously impacted by Sufu deletion, but are less sensitive to downstream genetic manipulations to reduce Gli2 expression or overexpress a Gli3R mimic, compared with anterior lobules. Transcriptome sequencing uncovered new Sufu targets, especially Fgf8, which is upregulated in Sufu-mutant GCPs. We demonstrate that Fgf8 is necessary and sufficient to drive Sufu-mutant GCP proliferation. This study reveals new insights into the spatial and temporal regulation of cerebellar Shh-Gli signalling, while uncovering new targets, such as Fgf8.

Acute toxicity of plants mixture used in traditional treatment of edema and colic renal in Morocco

Abstract The use of plants for the treatment of edema and colic renal in Morocco is widespread. The purpose of this research was to evaluate the toxic effect of aqueous extracts of plants mixture used in the traditional treatment of edema and renal colic in rats. For acute toxicity, a single dose of 300, 500, 2000, and 6000 mg/kg (lethal dose) and 10 ml/kg (traditional dose) body weight of an aqueous extract of plants mixture, were administered orally to Wistar rats. The animals were observed for any behavioral changes, neurological changes, changes in autonomic profiles, and mortality. The body weights were measured each day for the 14 days following the aqueous extract of plants mixture administration. Calculation of relative organ weight, hematological, biochemical analysis, and histopathology evaluation was carried out. No mortality and no statistically significant decrease in body weight were observed. The kidneys and the liver showed a statistically significant decrease in the relative organ weight of the treated groups of rats when compared to the control group, whereas the spleen showed a statistically significant increase. For biochemical parameters, a significant increase in Alanine aminotransferase, Aspartate aminotransferase and creatinine was noted. However, Alkaline phosphatase level showed a significant decrease. Furthermore, Hematologic parameters presented a significant increase in leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelets. Whereas, erythrocytes number and hemoglobin level were significantly increased. Histopathological evaluation revealed the major histology changes in the liver with lymphocytic inflammatory infiltrates at dose of 300 and 500 mg/kg body weight and plasmacytic inflammatory infiltrates at dose of 2000 mg/kg body weight, lethal dose and traditional dose in the central vein and lobule hepatic. Based on our results, the mixture of plants traditionally used in the treatment of edema and renal colic is toxic to the vital organs of the body.

Brachychiton populneus (Schott & Endl.) R.Br. ameliorate carbon tetrachloride induced oxidative stress through regulation of endoplasmic reticulum stress markers and inflammatory mediators in Sprague-Dawley male rats

In this study hepatoprotective aptitude of Brachychiton populneus against carbon tetrachloride (CCl4) instigated liver injuries in rats was investigated. High-performance liquid chromatography (HPLC) with a diode array detector (DAD) analysis of methanol extract of B. populneus (BPM) indicated existence of rutin, catechin and myricetin. Administration of CCl4 to rat decreased (p < 0.01) the level of catalase (CAT), total superoxide dismutase (SOD), peroxidase (POD), soluble protein and reduced glutathione (GSH) whereas elevated the concentration of H2O2, thiobarbituric acid reactive substances and nitrite in hepatic samples. In serum the level of hepatic markers; aspartate transaminase, alanine transaminase, alkaline phosphatase and total bilirubin increased with CCl4 treatment against control animals. In hepatic samples the expression level of endoplasmic reticulum stress associated genes like glucose regulated protein (GRP78), x-box binding protein- 1 total (XBP-1 t), x-box binding protein- 1 spliced (XBP-1 s), x-box binding protein- 1 unspliced (XBP-1 u), glutamate-cysteine ligase catalytic subunit (GCLC) and pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was elevated many fold with CCl4 administration to rat. Co-administration of BPM along with CCl4 to rats decreased (p < 0.05) the expression of above genes except GCLC where expression level was enhanced as compared to CCl4 treatment. Histopathology of liver showed injuries of hepatocytes, infiltration of leukocytes and damaged central lobule in CCl4 treated rats. However, BPM administration to CCl4 intoxicated rats restored the altered parameters towards the control rats. These results suggested the presence of antioxidant and anti-inflammatory constituents in methanol extract of B. populneus.

F192. Role of multimodal extra and intraoperative Stereoelectroencephalography (sEEG) monitoring in tailoring staged surgical resection in patients with eloquent cortex (Rolandic) pharmacoresistant epilepsy

Introduction To describe the feasibility, safety and seizure outcome of patients with medically intractable rolandic epilepsy(RE) who underwent staged resections guided by multimodal extra and intraoperative SEEG recordings. Methods We retrospectively studied and analyzed patients, who underwent extra and intraoperative intracranial invasive stereoEEG monitoring, data related to semiology, non-invasive electrophysiology, imaging, type of resection, complications, surgical pathology results and seizure outcome from January 2015 through September 2017, under Cleveland Clinic IRB. Results Five patients were identified as having intractable RE based on analysis of pre-surgical evaluation using 3T magnetic resonance imaging (MRI), magnetoencephalography(MEG) and positron emission tomography (PET). Preoperative magnetic resonance imaging were considered nonlesional in all five patients but after the pre-surgical evaluation, there were abnormal sulcation pattern or increased signal in white matter were noticed which are of unknown significance. All five patients were underwent sEEG implantation with hypothesis of peri-rolandic or paracentral lobule regions being epileptogenic. Extra-operative sEEG data in all patients showed ictal onset zone involving rolandic cortex (hand knob and paracentral lobule), premotor and/or supplementary motor area (SMA). In two patients, hand knob rolandic cortex was the region of interest The other three being paracentral lobule (leg motor). Given all the data (semiology, sEEG data and pre-sugical evaluation), the conclusion of epileptogenic zone (EZ) being close proximity to eloquent cortex. Given the semiology, staged resection approach with continuous sEEG recording was performed in the operating room. Resection of interictally active non-eloquent cortex electrodes was performed first guided by real-time intraoperative sEEG (electrophysiology) data. The resection was also guided by the sEEG electrode in three dimensions. Resolution of rolandic hand motor spike activities was documented after resection of SMA in three patients, cingulate and pre-motor areas in one patient. In the last patient, hand sensory area was resected sparing motor cortex. Three out of five patients did not have any deficit but two had mild foot drop. Pathology showed focal cortical dysplasia type (IB, IIA, and IIB) and a possible vascular malformation in another. All patients were reported to be seizure free at follow up period of 6–28 months. Conclusion Taken into account of hyper-synchronous connectivity in frontal and parietal rolandic regions, we present a case series of patients who underwent staged resections guided by a novel multimodal method of invasive monitoring. The results of this highly selected group of patients testify for the feasibility and safety of a novel multimodal method of invasive monitoring, combining the benefits of both intra and extra-operative SEEG recording, especially operating around the central lobule near hand knob regions.

Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking

Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity.

Disrupted brain network topology in chronic insomnia disorder: A resting-state fMRI study.

This study investigated the topological characteristics of brain functional networks in chronic insomnia disorder (CID) patients. The resting-state functional magnetic resonance imaging and graph theory analysis method were applied to investigate the brain functional connectome patterns among 45 CID patients and 32 healthy controls. The brain functional connectome was constructed by thresholding partial correlation matrices of 90 brain regions from an automated anatomical labeling atlas. The topologic properties of brain functional connectomes at both global and nodal levels were tested. The CID patients had decreased number of module (p = .014) and hierarchy (p = .038), and increased assortativity (p = .035). Furthermore, some brain regions located in the default mode network, dorsal attention network, and sensory-motor network in these patients showed altered nodal centralities. Within these areas, the node betweenness of right central paracentral lobule had positive correlation with the Pittsburgh Sleep Quality Index score (R = 0.319, p = .039). The results imply that functional disruptions of CID patients may be related to disruptions in global and regional topological organization of the brain functional connectome, and provide new and important insights to understand the pathophysiological mechanisms of CID.

Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARγ expression.

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Crus I in the Rodent Cerebellum: Its Homology to Crus I and II in the Primate Cerebellum and Its Anatomical Uniqueness Among Neighboring Lobules.

In the human cerebellum, the crus I and crus II lobules (or the ansiform lobule), which are implicated in cognitive and visuomotor functions, are significantly expanded compared to other anterior and posterior lobules, which are involved mainly in somatosensorimotor function. In applying rodent models, it is essential to identify the lobules that are homologous to human crus I and crus II. Observation of the lobular structure in human, macaque, marmoset, rat, and mouse has indicated that human crus I and II are homologous to crus I in rodents (referred to as "ansiform area, AA"). This new lobular definition is supported by lobule-based mapping of the olivocerebellar climbing fiber and Purkinje cell (PC) projection patterns in rodents; crus II and simple lobules are innervated by the mediocaudal part of each inferior olive subnucleus and project to the dorsal part of the cerebellar nuclei, while crus I (or the AA) is innervated by the rostrolateral part of each inferior olive subnucleus and projects to the ventral part of the cerebellar nuclei. Concerning zebrin stripes, the central lobules (lobules VI-VII and AA or crus I in rodents) show a laterally expanded arrangement solely of positive stripes. Our recent analysis has shown that this arrangement of zebrin-positive stripes in the AA originates from their developmental process. Between E14.5 and E17.5, lateral protrusion and shift has been observed in the domains of protocadherin 10-positive PC subsets (which would become zebrin-positive later) in the central area of the immature cerebellum that eventually becomes lobules VI-VII and AA or crus I. These data suggest that the AA (or crus I in rodents) is a unique lobule in the mammalian cerebellum which is characterized by distinct connectivity from neighboring lobules, a massive expansion in skillful primates, and the formation of longitudinal stripes different from that in neighboring anterior and posterior lobules.

Spatial rearrangement of Purkinje cell subsets forms the transverse and longitudinal compartmentalization in the mouse embryonic cerebellum

AbstractTransversely oriented lobules and longitudinally arrayed stripes of Purkinje cell subsets subdivide the cerebellar cortex into multiple compartments that are involved in diverse functions. In the mammalian cerebellum, anterior, and posterior lobules, which are involved in somatosensorimotor function, show an alternation of aldolase C (zebrin II) ‐positive and ‐negative stripes, whereas the central lobules (lobules VIb–VII and crus I), which are implicated in nonmotor functions, show a laterally expanded arrangement solely of aldolase C‐positive stripes. To understand the developmental process of this compartmental pattern, we identified groups of Purkinje cell subsets in the entire mouse cerebellum at embryonic day (E) 14.5 by staining Purkinje cell subset markers. We then tracked four major domains of Protocadherin 10 (Pcdh10)‐positive Purkinje cell subsets (medial, dorsal, central, and mid‐lateral subsets), which were clearly demarcated during E14.5–17.5. These domains of Purkinje cell subsets shifted predominantly in the longitudinal direction to be positioned in the anterior and posterior lobules. However, a particular portion of the medial and mid‐lateral domains, and the whole of the central domain shift in the lateral direction to be positioned in the central lobules. The results indicate that while the longitudinal shift of domains of Purkinje cell subsets forms the longitudinally striped compartments in the anterior and posterior cerebellum, the lateral shift of particular domains of Purkinje cell subsets underlies the laterally expanded arrangement of stripes in central lobules. Thus, the rearrangement of Purkinje cell subsets in the embryonic cerebellum is critically related to the compartmental organization in the mammalian cerebellum.

Spatial rearrangement of Purkinje cell subsets forms the transverse and longitudinal compartmentalization in the mouse embryonic cerebellum.

Transversely oriented lobules and longitudinally arrayed stripes of Purkinje cell subsets subdivide the cerebellar cortex into multiple compartments that are involved in diverse functions. In the mammalian cerebellum, anterior, and posterior lobules, which are involved in somatosensorimotor function, show an alternation of aldolase C (zebrin II) -positive and -negative stripes, whereas the central lobules (lobules VIb-VII and crus I), which are implicated in nonmotor functions, show a laterally expanded arrangement solely of aldolase C-positive stripes. To understand the developmental process of this compartmental pattern, we identified groups of Purkinje cell subsets in the entire mouse cerebellum at embryonic day (E) 14.5 by staining Purkinje cell subset markers. We then tracked four major domains of Protocadherin 10 (Pcdh10)-positive Purkinje cell subsets (medial, dorsal, central, and mid-lateral subsets), which were clearly demarcated during E14.5-17.5. These domains of Purkinje cell subsets shifted predominantly in the longitudinal direction to be positioned in the anterior and posterior lobules. However, a particular portion of the medial and mid-lateral domains, and the whole of the central domain shift in the lateral direction to be positioned in the central lobules. The results indicate that while the longitudinal shift of domains of Purkinje cell subsets forms the longitudinally striped compartments in the anterior and posterior cerebellum, the lateral shift of particular domains of Purkinje cell subsets underlies the laterally expanded arrangement of stripes in central lobules. Thus, the rearrangement of Purkinje cell subsets in the embryonic cerebellum is critically related to the compartmental organization in the mammalian cerebellum.