Lateral Ventricle Research Articles

Chronic central nervous system leptin administration attenuates kidney dysfunction and injury in a model of ischemia/reperfusion-induced acute kidney injury.

In the present study, we examined whether chronic intracerebroventricular (ICV) leptin administration protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Twelve-week-old male rats were implanted with an ICV cannula into the right lateral ventricle, and 8-10 days after surgery, leptin (0.021 µg/h, n = 8) or saline vehicle (0.5 µL/h, n = 8) was infused via osmotic minipump connected to the ICV cannula for 12 days. On day 8 of leptin or vehicle infusion, rats were submitted to unilateral ischemia/reperfusion (UIR) by clamping the left pedicle for 30 min. To control for leptin-induced reductions in food intake, the vehicle-treated group was pair-fed (UIR-PF) to match the same amount of food consumed by leptin-treated (UIR-Leptin) rats. On the 12th day of leptin or vehicle infusion (fourth day after AKI), single-left kidney glomerular filtration rate (GFR) was measured, blood samples were collected to quantify white blood cells, and kidneys were collected for histological assessment of injury. UIR-Leptin-treated rats showed reduced right and left kidney weights (right: 1,040 ± 24 vs. 1,281 ± 36 mg; left: 1,127 ± 71 vs. 1,707 ± 45 mg, for UIR-Leptin and UIR-PF, respectively). ICV leptin infusion improved GFR (0.50 ± 0.06 vs. 0.13 ± 0.03 mL/min/g kidney wt) and reduced kidney injury scores. ICV leptin treatment also attenuated the reduction in circulating adiponectin levels that was observed in UIR-PF rats and increased the circulating white blood cells count compared with UIR-PF rats (16.3 ± 1.3 vs. 9.8 ± 0.6 k/µL). Therefore, we show that leptin, via its actions on the central nervous system, confers significant protection against major kidney dysfunction and injury in a model of ischemia/reperfusion-induced AKI.NEW & NOTEWORTHY A major new finding of this study is that chronic activation of leptin receptors in the CNS markedly attenuates acute kidney injury and protects against severe renal dysfunction after ischemia/reperfusion, independently of leptin's anorexic effects.

Fetal Brain MRI Findings in Myotonic Dystrophy and Considerations for Prenatal Genetic Testing.

Congenital myotonic dystrophy type 1 (DM1) is a rare congenital neuromuscular disorder associated with high morbidity and potential early mortality requiring lifelong symptomatic management. Prenatal presentations of DM1 have been associated with nonspecific ultrasound findings such as clubbed foot, polyhydramnios, ventriculomegaly, and decreased fetal movement, but many cases of DM1 have no ultrasound anomalies. We sought to compare the clinical course and prenatal imaging findings in two cases of DM1 using retrospective chart review. This report demonstrates potential expansion of the prenatal phenotype of DM1 including fetal SVT and frontal bossing. Both cases shared unique prenatal imaging features of lateral ventricle dilation involving the anterior bodies and frontal horns on fetal MRI. Because congenital DM1 is most often maternally inherited, attention to maternal symptoms, physical examination, and family history can be helpful in recognizing cases. Molecular diagnosis of DM1 requires specialized testing of the 3' untranslated region of the DMPK gene, and DM1 will not be detected by current standard prenatal genetic testing with microarray, karyotype, or exome sequencing.

Glioblastoma and its interaction with neurogenesis

Glioblastoma (GBM) is the most frequent and aggressive malignant primary tumor of the central nervous system in adults, with an incidence of 3.23 per 100,000 people. Despite the existence of various therapeutic approaches, the absence of a cure and the unfavorable prognosis persist for this neoplasm, with a median survival of approximately 8-15 months and a 5-year survival rate of 6.9%. In this review, we address the epidemiology, histopathology, molecular characteristics, and treatment of GBM. We highlight the relationship of GBM with the microenvironment in the lateral ventricle wall and the cerebrospinal fluid. The location of GBM in this region results in more aggressive tumors and shorter life expectancy for patients. Understanding the malignancy mechanisms that hinder remission, treatment, and positive prognosis opens the possibility of improving diagnostic and therapeutic interventions against GBM.

The normalization trend of ventricular morphology after lateral ventricular tumor resection without additional diversion.

Intraventricular tumors frequently provoke alterations in ventricular morphology. This study aims to quantificational assess perioperative dynamic fluctuations in the cerebrospinal fluid (CSF) volume within the lateral ventricles of patients harboring lateral ventricular tumors. A retrospective review encompassing 90 patients who underwent surgical intervention for lateral ventricular tumors at our institution was undertaken. Comprehensive observations at multiple perioperative time points were conducted, and LVCV analyses were performed to delineate the longitudinal dynamic alterations in ventricular morphology. Additionally, LVCV measurements were juxtaposed with data from 19 healthy subjects to stratify patients into two cohorts: those exhibiting preoperative increased LVCV and those without such changes. After surgical excision of intraventricular tumors, alterations in LVCV were compared between these cohorts, with a factor analysis undertaken specifically among patients demonstrating increased LVCV to elucidate potential influencing variables. 40 patients (44.4%) diagnosed with intraventricular tumors presenting with enlarged preoperative LVCV [74.6 (49.3-101.8) cm3] compared with the normal subject group, and the LVCV demonstrated a significant postoperative [41.3 (27.6-67.5) cm3] reduction in 3 months (p < 0.001). Meanwhile, 50 patients (55.6%) without LVCV enlargement [14.5 (8.1-21.0) cm3] experienced a notable increase following surgery in 3 months [20.2 (14.1-33.3) cm3, p = 0.002]. Preoperative increased LVCV is an important factor leading to the increased LVCV postoperatively (p = 0.022, OR = 26.239), however, compared to healthy subjects, both groups exhibited a trend toward normalization of LVCV value postoperatively (p = 0.165, p = 0.072, respectively). Following appropriate surgical excision of the tumor, the preoperative increased LVCV associated with intraventricular tumors does not hinder the normalization trend of ventricular morphology. Not all ventricular dilation requires preventive long-term external ventricular drainage and aggressive ventriculoperitoneal shunt treatment.

Frontal Horn of Lateral Ventricle of Brain and Its Relation with Age, Gender and Side: Morphometric Study by Computed Tomography among Bangladeshi Population

Background: Knowledge of the baseline reference value of frontal horn size is necessary for the initial and precise analysis of ventriculomegaly. The purpose of this study was to determine the size of frontal horn of lateral ventricle and its relation with age, gender and side among adult Bangladeshi population of Chattogram district. Materials and methods: This cross-sectional analytical study was conducted during the period from July 2022 to June 2023 in the Department of Anatomy, Chittagong Medical College, Chattogram, upon 150 respondents of 20-60 years who had normal Computed Tomography (CT) scans as reported by an expert radiologist. For statistical analysis, Mann-Whitney U test, Wilcoxon signed rank test and ANOVA test were done. p-value was considered significant if it was &lt;0.05 at 95% level of confidence. Results: The mean right and left frontal horn length was 25.50 (±3.95) mm and 25.28 (±4.04) mm respectively. The length of the frontal horn of both right and left sided lateral ventricle were significantly higher in male than that of female (p&lt;0.01). Spearman's correlation coefficient indicated positive linear correlation of length of frontal horn (Right and left side) with age, insignificant in right side (p=0.061) but significant in left side (p=0.046). Conclusion: Morphometric analysis of the frontal horn of the lateral ventricles among the Bangladeshi population produced a number of significant results that may help with the early diagnosis and treatment of neurological diseases that are particular to gender and age. These findings can be validated and expanded upon in future research using bigger sample sizes and cutting-edge imaging methods. IAHS Medical Journal Vol 7(1), June 2024; 54-59

NIMG-61. TRANSVENTRICULAR MIGRATION OF CESIUM-131 BRACHYTHERAPY SEEDS TO THE SACRAL THECAL SAC IN A PATIENT TREATED FOR RECURRENT GLIOBLASTOMA

Abstract Cesium-131 brachytherapy (GammaTileTM) is a relatively new form of surgically targeted radiation therapy for recurrent glioblastoma. While seed migration is a well-documented complication of solid tumor brachytherapy, it has not been reported in the treatment of glioblastoma. Here, we describe a rare occurrence of seed migration in a 71-year-old patient treated for recurrent left temporal lobe glioblastoma. The GammaTile is comprised of a resorbable collagen matrix containing four titanium-encapsulated radioactive Cs-131 seeds. Each seed emits a localized dose of radiation with a 9.7-day half-life. To prevent displacement from the resection cavity, oxidized regenerated cellulose (SurgicelTM) was applied to the cavity surface under the tiles and fibrin sealant (TisseelTM) was applied over the tiles. Margins of the lateral ventricles were not breached during the surgery and surface was non-ulcerated. The tiles remained in place on follow-up imaging for at least 7 weeks. At least 97% of the prescribed dose was delivered before seed migration. Bevacizumab systemic treatment was initiated. Abdominal CT obtained after 3 months incidentally noted migration of 2 seeds to the sacral spinal canal. Additional seeds had migrated to the suprasellar region, left lateral ventricle, and lateral cerebellomedullary cistern. Despite seed migration, the patient maintained progression-free survival for at least 10 months, with at least 30 months of overall survival from the time of diagnosis. Although the patient did not experience any symptoms related to seed migration, this has the potential to cause radiation-related toxicity to healthy tissue, particularly if it occurs early after surgery. The use of bevacizumab may have contributed to penetration of the lateral ventricle. Despite meticulous surgical technique, the potential for seed migration should be considered during treatment planning when using anti-angiogenic therapies. Further research is needed to better understand the factors contributing to seed migration and to develop strategies for minimizing this risk.

STEM-15. THE IMPACT OF TUMOR TREATING FIELDS (TTFIELDS) ON CANCER STEM-LIKE CELLS ISOLATED FROM THE SUB-VENTRICULAR ZONE OF GLIOBLASTOMA PATIENTS

Abstract Treatment of glioblastoma (GBM) is challenging due to its heterogeneous nature, invasive potential, and poor response to standard-of-care treatments. Areas of residual disease represent the source of the recurrent tumor that is fatal for GBM patients. However, targeting the residual disease is not offered as part of the standard of care because these areas are difficult to identify. Our laboratory was the first to identify and characterize residual disease in the sub-ventricular zone (SVZ) of the lateral ventricles of GBM patients. In this study, we are examining the impact of Tumor Treating Fields (TTFields) on treatment-resistant cancer stem-like cells (CSCs) isolated from the SVZ of 12 GBM patients using single-cell transcriptomics and functional phenotyping analysis. These cells are maintained in conditions that preserve the molecular profile of the original patient tumor, thus representing bona fide models to study the impact of TTFields on GBM residual disease. Our results show that: CSCs isolated from the SVZ from different individuals show different sensitivity to TTFields, the anti-proliferative effects of TTFields are maintained at different plating cell densities, and when the frequency of TTFields increase from 50 kHz to 200 kHz, CSCs undergo morphological changes (e.g., fewer spheres and fewer connections between cells). We used 100 μM Temozolomide and ionizing radiation (10 Gy) mimicking the standard of care of GBM patients, and the growth of the treatment-resistant CSCs was inhibited by TTFields (200 kHz). To elucidate how TTFields impact the cellular and molecular characteristics of CSCs in their microenvironment, ongoing work focuses on single-cell transcriptomics and functional phenotyping analysis. These results extend our understanding of the mechanisms of action of TTFields, specifically on how TTFields have the potential to alter the cytokine-mediated cross-talk between CSCs of the SVZ and their microenvironment.

NCMP-01. EARLY RECURRENCE OF GLIOBLASTOMA MULTIFORM INVOLVING MULTIPLE BRAIN REGIONS ASSOCIATED WITH MUTATIONS IN EXON 4 OF ISOCITRATE DEHYDROGENASE 1 COMPLICATED BY GADOLINIUM-INDUCED ACUTE KIDNEY FAILURE: A CASE REPORT

Abstract BACKGROUND Glioblastoma multiform (GBM) remains one of the most aggressive primary brain tumors with high recurrence rates. Case presentation We present a case of a 43-year-old female, Yira, diagnosed with early recurrence of GBM involving multiple brain regions, accompanied by mutations in exon 4 of isocitrate dehydrogenase 1 (IDH1), a marker associated with poor prognosis. Additionally, this case was complicated by gadolinium-induced acute kidney failure on postoperative day 3. The patient initially presented with progressive neurological symptoms, including headache and cognitive decline. Multiplanar multiecho MRI of the brain was performed with IV contrast in orthogonal plane and revealed a moderate sized multilobulated heterogeneously and predominantly peripherally enhancing mass lesion with irregular margins and central non enhancing areas of necrosis arising from the right corona radiata, insular cortex, external capsule, lentiform nucleus, temporal, and frontal white matter with blood products. Perilesional edema was seen. Effacement of sulcal spaces. Right sylvian fissure, compression over right ventricle and midline shift of 8mm toward left side. There was dilatation of the left lateral ventricle with periventricular cerebrospinal fluid ooze. Uncal herniation was right side. On MR spectroscopy large choline, creatinine levels were seen in the lesion with reduced N-acetyl aspartate levels as compared to the normal parenchyma. Findings were suggestive of neoplastic lesion mostly high-grade glioma. Polymerase chain reaction sequencing confirmed missense mutation R132H in exon 4 of isocitrate dehydrogenase 1 gene. Despite maximal safe surgical resection, the patient developed recurrent GBM within three months, with gadolinium-based contrast agent exposure leading to acute kidney injury. CONCLUSION The combination of aggressive tumor behavior and complications from contrast agent administration highlights the challenges in managing recurrent GBM. This case underscores the importance of vigilant monitoring for complications in GBM patients, particularly those with IDH1 mutations, and the need for further research into novel therapeutic strategies.

EPID-35. COLLISION TUMORS AT THE SKULL BASE: UNVEILING A PETROCLIVAL MENINGIOMA COEXISTING WITH A GROWTH HORMONE-PRODUCING PITUITARY ADENOMA

Abstract Collision tumors are rare occurrences characterized by coexistence of two histologically different tumor types within the same anatomical location. While collision tumors involving skull base meningiomas and pituitary adenomas are uncommon, they pose distinct diagnostic challenges. We report the case of a 57-year-old female initially diagnosed with petroclival meningioma WHO 1, subsequently found to harbor a collision tumor with a growth hormone-producing pituitary adenoma. The patient initially presented with aphasia, right-sided weakness, and gait instability, prompting a diagnosed of left petroclival mass with left temporal horn entrapment. Patient underwent craniotomy and partial resection of the tumor in 2022 and was diagnosed with meningothelial meningioma, WHO1. The patient had history of uncontrolled diabetes and physical features of large hands with hypertrophied terminal phalangeal tufts but patient reported that she has had similar hands since childbirths for decades. Screening pituitary function tests were ordered due to the petroclival meningioma involving suprasellar region, revealing significantly elevated growth hormone, and insulin-like growth factor-1(IGF-1) levels, raising suspicion for pituitary adenoma. Subsequent endoscopic resection of the sellar mass via a transsphenoidal approach in 2024 confirmed the presence of somatotroph pituitary neuroendocrine tumor. Retrospectively growth hormone producing pituitary adenoma likely contributed to patient’s uncontrolled diabetes and coarse, large hands. This case highlights the importance of a high index of suspicion for collision tumors, particularly in patients with skull base tumors involving supra sellar region, especially when presenting with atypical clinical features.

Comprehensive Morphometric Analysis to Identify Key Neuroimaging Biomarkers for the Diagnosis of Adult Hydrocephalus Using Artificial Intelligence.

Hydrocephalus involves abnormal cerebrospinal fluid accumulation in brain ventricles. Early and accurate diagnosis is crucial for timely intervention and preventing progressive neurological deterioration. The aim of this study was to identify key neuroimaging biomarkers for the diagnosis of hydrocephalus using artificial intelligence to develop practical and accurate diagnostic tools for neurosurgeons. Fifteen 1-dimensional (1-D) neuroimaging parameters and ventricular volume of adult patients with non-normal pressure hydrocephalus and healthy subjects were measured using manual image processing, and 10 morphometric indices were also calculated. The data set was analyzed using 8 machine, ensemble, and deep learning classifiers to predict hydrocephalus. SHapley Additive exPlanations (SHAP) feature importance analysis identified key neuroimaging diagnostic biomarkers. Gradient Boosting achieved the highest performance, with an accuracy of 0.94 and an area under the curve of 0.97. SHAP analysis identified ventricular volume as the most important parameter. Given the challenges of measuring volume for clinicians, we identified key 1-D morphometric biomarkers that are easily measurable yet provide similar classifier performance. The results showed that the frontal-temporal horn ratio, modified Evan index, modified cella media index, sagittal maximum lateral ventricle height, and coronal posterior callosal angle are key 1-D diagnostic biomarkers. Notably, higher modified Evan index, modified cella media index, and sagittal maximum lateral ventricle height, and lower frontal-temporal horn ratio and coronal posterior callosal angle values were associated with hydrocephalus prediction. The results also elucidated the relationships between these key 1-D morphometric parameters and ventricular volume, providing potential diagnostic insights. This study highlights the importance of a multifaceted diagnostic approach incorporating 5 easily measurable 1-D neuroimaging biomarkers for neurosurgeons to differentiate non-normal pressure hydrocephalus from healthy subjects. Incorporating our artificial intelligence model, interpreted through SHAP analysis, into routine clinical workflows may transform the diagnostic landscape for hydrocephalus by standardizing diagnosis and overcoming the limitations of visual evaluations, particularly in early stages and challenging cases.

The impact of real-time ultrasound guidance on ventricular catheter placement in cerebrospinal fluid shunts - a single-center study.

Misplacement of ventricular catheters during shunt surgery occurs in 40% of cases using a freehand technique and therefore represents a risk for early shunt failure. The goal of this retrospective, single-center study is to analyze the impact of real-time ultrasound guidance on ventricular catheter positioning and early outcome of shunt survival. We analyzed the charts and images of all patients who underwent shunt surgery from 09/2017 to 12/2022 and compared the position of the ventricular catheter using the freehand technique and real-time ultrasound guidance. Central catheter position was graded as grade I (optimal), II (contact with ventricle structures or contralateral), and III (misplacement). A ventricular catheter was placed in 244 patients using real-time US guidance and in 506 patients using a freehand technique. The mean age (53.4 and 53.6 years, respectively) and the preoperative frontal occipital horn ratio (FOHR; 0.47 versus 0.44) were almost equal in both groups. In the study group, grade I catheter position was achieved in 64% of cases, grade II in 34%, and grade III in 2%. The control group showed grade I position in 45%, grade II in 32%, and grade III in 23% of cases (p<0.05). An early central catheter failure rate was the highest in grade III (40.5%) compared to 4% in grade I. Our data demonstrate that real-time US guidance leads to a significant improvement in ventricular catheter placement. Consequently, early shunt revisions decrease significantly. Further prospective, randomized, and controlled studies comparing the standard method to real-time ultrasound catheter placement are required.

Diffusion-derived intravoxel-incoherent motion anisotropy relates to CSF and blood flow.

Multi-b-value diffusion MRI was acquired in 32 gradient directions for 11 healthy volunteers, and in six directions for 29 patients with cSVD and 14 controls at 3 T. A physics-informed neural network was used to estimate intravoxel incoherent motion (IVIM)-DTI model parameters, including the parenchymal slow diffusion (D-)tensor and the pseudo-diffusion (D*)-tensor, from which the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were derived. Comparisons of D*-tensor metrics were made between lateral, third, and fourth ventricles and between the middle cerebral arteries and superior sagittal sinus. Group differences in D*-tensor metrics in normal-appearing white matter were analyzed using multivariable linear regression, correcting for age and sex. D*-anisotropy aligned well with CSF flow and arterial blood flow. FA(D*), MD(D*), AD(D*), and RD(D*) were highest in the third, moderate in the fourth, and lowest in the lateral ventricles. The arteries showed higher MD(D*), AD(D*), and RD(D*) than the sagittal sinus. Higher FA(D*) in the normal-appearing white matter was related to cSVD diagnosis and older age, suggesting microvascular architecture alterations. Multi-b-value, multi-directional diffusion analysis using the IVIM-DTI model enables assessment of the cerebral microstructure, fluid flow, and microvascular architecture, providing information on neurodegeneration, glymphatic waste clearance, and the vasculature in one measurement.

Analysis of clinical phenotypes and genetic variations in two pedigrees affected with Weiss-Kruszka syndrome.

Weiss-Kruszka syndrome (WSKA) is a rare autosomal dominant syndrome characterized by multiple congenital anomalies caused by variants in the zinc finger protein 462 gene (ZNF462). About 40 cases of Weiss-Kruszka syndrome have been reported worldwide, and the aim of this study was to investigate the genetic causes of three patients from two Weiss-Kruszka syndrome family pedigrees with the aim of accumulating more data on the disease. To explore the clinical and genetic characteristics of two pedigrees with Weiss-Kruszka syndrome. The clinical data and family history of patients and family members of two pedigrees with Weiss-Kruszka syndrome were collected, and the pathogenic genes of the patients were analysed by whole-exon sequencing. Suspicious variants were verified by Sanger sequencing verification and bioinformatics prediction. Proband 1 has developmental delay, autistic behaviour, and abnormal electroencephalogram results. WES revealed a classical heterozygous c.6696-2A > C splice variant of the ZNF462 gene, which was detected in neither parent. This position was conserved, and the variant was predicted to be deleterious. Minigene assays revealed that three types of aberrantly spliced mRNAs were produced. MRI of proband 2 suggested dysplasia of the corpus callosum with the formation of hemispheric cleft cysts, with a teardrop-like appearance in the lateral ventricle. WES revealed that a heterozygous c.4891C > T:p. The Glu1631Ter nonsense variant of the ZNF462 gene was inherited from her mother. According to the guidelines of the American Society of Medical Genetics and combined with its clinical manifestations, c.6696-2A > C and c.4891C > T:p. Glu1631Ter was determined to be a possible pathogenic variant. The c.6696-2A>C and c.4891C > T:p.Glu1631Ter of the ZNF462 gene likely underlies Weiss-Kruszka syndrome in children (foetus), which enriches the variant spectrum of Chinese patients with Weiss-Kruszka syndrome and provides a basis for prenatal diagnosis and genetic counselling.

Childhood Community Disadvantage and MRI-Derived Structural Brain Integrity After Age 65 Years

Prior studies associate late-life community disadvantage with worse brain health. It is relatively unknown if childhood community disadvantage associates with late-life brain health. To test associations between childhood residence in an economically disadvantaged community, individual income and education, and late-life cortical brain volumes and white matter integrity. This cohort study was conducted in the ongoing harmonized cohorts KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences Study; initiated 2017) and STAR (Study of Healthy Aging in African Americans; initiated 2018) using all available data collected out of a regional integrated health care delivery network in California between cohort initiation and analysis initiation in June 2023. Eligible participants were Kaiser Permanente Northern California member ages 65 years or older. Data were analyzed between June and November 2023. Residence at birth was geocoded and linked to historical Area Deprivation Indices (ADI). ADI is a nationally ranked percentile; community disadvantage was defined as ADI of 80 or higher. Regional brain volumes and white matter integrity measures were derived from a random subset of participants who underwent 3T magnetic resonance imaging. Models adjusted for race and ethnicity, sex, and parental education. Of a total 2161 individuals in the combined cohort, 443 individuals were eligible for imaging (mean [SD] age, 76.3 [6.5] years; 253 female [57.1%]; 56 Asian [12.6%], 212 Black [47.9%], 67 Latino [15.1%], 109 White [24.6%]). Imaging participants had a mean (SD) 15.0 (2.5) years of education, and 183 (41.3%) earned $55 000 to $99 999 annually. Fifty-four participants (12.2%) resided in a disadvantaged childhood community. Childhood community disadvantage was associated with smaller gray matter volumes overall (-0.39 cm3; 95% CI, -0.65 to -0.10 cm3) and in the cerebellum (-0.39 cm3; 95% CI, -0.66 to -0.09 cm3), hippocampus (-0.37 cm3; 95% CI, -0.68 to -0.04 cm3), and parietal cortex (-0.25 cm3; 95% CI, -0.46 to -0.04 cm3) and larger mean lateral ventricle (0.44 cm3; 95% CI, 0.12 to 0.74 cm3), third ventricle (0.28 cm3; 95% CI, 0.03 to 0.55 cm3), and white matter hyperintensity volume (0.31 cm3; 95% CI, 0.06 to 0.56 cm3). Educational attainment and late-life income did not mediate these associations. In this cohort study of racially and ethnically diverse health plan members, childhood community disadvantage was associated with worse late-life brain health independent of individual socioeconomic status. Future work should explore alternative pathways (eg, cardiovascular health) that may explain observed associations.

The number and distribution of proliferating cells in the rat’s rostral migratory stream as identified by means of two different proliferation markers

ABSTRACT In the brains of adult rodents, the cells arising in the subventricular zone of the lateral ventricles maintain the ability to divide when migrating to the olfactory bulb along the rostral migratory stream (RMS). Dividing cells in the RMS are most frequently revealed through immunohistochemical detection of an exogenous marker of proliferation, 5-Bromo-2-deoxyuridine (BrdU), which incorporates into DNA during the S-phase of mitosis. The more recently recognized antigen Ki-67 (also known as Kiel-67 and MKI67), an endogenous protein expressed in nuclei at all stages of mitosis, is also used for proliferation detection. BrdU and Ki-67 are often used as alternative methods, but they have not previously been compared in the RMS. We analyzed the numbers and distribution of cells labeled either with BrdU or Ki-67 within the RMS of adult rats. The first group of animals received a single i.p. dose of BrdU. In the second group, dividing cells were visualized by Ki-67 immunohistochemistry. Some sections from brains of BrdU-treated rats were also immunostained for Ki-67. Labeled cells were counted in the three anatomical parts of the RMS (vertical arm, elbow and horizontal arm) using a method for unbiased estimation of cell density. The distribution of proliferating cells was similar for both markers. Most BrdU and Ki-67 positive cells were located in the vertical arm and in the elbow, but a caudo-rostral reduction in cell divisions was more evident with Ki-67 labeling. The number of Ki-67 positive cells significantly exceeded the number of BrdU positive cells in all parts of the RMS. Our results indicate that BrdU and Ki-67 are not interchangeable markers for evaluation of proliferative activity in the RMS.

Association of depression with longitudinal changes in brain structure across the lifespan: A mendelian randomization study.

Understanding the impact of depression on brain aging benefits the prognosis of this disease and of the risk that other age-related brain disorders will develop in the same population. The aim of the present study was to explore the genetic effect of depression on longitudinal changes in brain structure throughout the lifespan using a Mendelian randomization approach. Summary data from a genome-wide association study of 195,321 to 377,277 participants in the FinnGen consortium were used to predict depression, anxiety disorders, mood disorders, and antidepressant use genetically. Data from 15,640 participants in the ENIGMA consortium were included to predict changes in 15 brain structures throughout the lifespan. The causal relationship between these depressive traits and the brain structure parameters was assessed by two-sample Mendelian randomization (including inverse-variance weighted). Sensitivity analyses were conducted for quality control. Depression slowed the decrease of cortical gray matter volume significantly throughout the lifespan (p = 0.001). Depression, anxiety, and mood disorders nominally decreased the rates of change of volume in the cerebellum gray matter, lateral ventricles, and cortical gray matter throughout the lifespan (p = 0.048, p = 0.021, p = 0.038, respectively). Antidepressants did not affect these rates of change significantly (p > 0.05). Sensitivity analyses confirmed the reliability of this study. Depression and its main symptoms have a slight effect on longitudinal changes in a few brain structures throughout the lifespan at the genetic level. These findings do not support the notion that depression affects macro-aging in the brain crucially.

Effects of lateral ventricle injection of 5,7-dihydroxytryptamine on neurons in the medial prefrontal cortex of rats: An electrophysiology study

The medial prefrontal cortex (mPFC) is closely associated with various psychopathologies in humans, and its dysfunction is invariably accompanied by abnormalities in the serotonin (5-hydroxytryptamine, 5-HT) system of the brain. In this study, in-vivo extracellular recording techniques were used to investigate changes in the excitability of pyramidal neurons and interneurons in the rat mPFC following injection of 5,7-dihydroxytryptamine (5,7-DHT) into the bilateral lateral ventricles to damage the serotoninergic neurons. The levels of 5-HT in the mPFC and dorsal raphe nucleus of rats were determined by high-performance liquid chromatography. The results showed that the levels of 5-HT were significantly reduced in the mPFC and dorsal raphe nucleus two weeks after injection of 5,7-DHT into the bilateral lateral ventricles, relative to the normal group. The discharge frequency of pyramidal neurons in the mPFC was markedly increased compared to the normal group, with a significant rise in burst discharge, while the average discharge frequency of interneurons was significantly reduced and tended towards irregular activity. The results of the study indicated that the brain’s 5-HT neurotransmitter system not only directly affects the activity of mPFC pyramidal neurons but also modulates the electrical activity of interneurons, thereby regulating the local microcircuitry within the mPFC and participating in its function.

Central treatment of neuropeptide-S attenuates cognitive dysfunction and hippocampal synaptic plasticity impairment by increasing CaMKII/GluR1 in hemiparkinsonian rats.

Neuropeptide-S (NPS) has been demonstrated to mitigate learning and memory deficits in experimental models of Parkinson's Disease (PD). Despite this, the precise mechanisms through which NPS exerts its influence on cognitive functions remain to be fully unknown. This study aims to elucidate the effects of central administration of NPS on learning and memory deficits associated with an experimental rat hemiparkinsonian model, examining both electrophysiological and molecular parameters. The hemiparkinsonian model was established via stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Central NPS (1 nmol, icv) was administered into the lateral ventricle via a cannula for seven consecutive days following the 6-OHDA lesion. The Morris water maze and object recognition tests were used to evaluate the rat's learning and memory abilities. Long-term potentiation (LTP) recordings were conducted to assess hippocampal synaptic plasticity. Immunohistochemistry was employed to determine the expression levels of phosphorylated CaMKII (pCaMKII), GluR1, and GluR2 in the hippocampus. The 6-OHDA-induced decline in cognitive performance was significantly (p < 0.05) improved in rats that received central NPS. In 6-OHDA-lesioned rats, NPS treatment significantly (p < 0.05) enhanced the amplitude of LTP at the dentate gyrus/perforant path synapses. Furthermore, NPS significantly (p < 0.05) increased the number of pCaMKII and GluR1 immunoreactive cells in the hippocampus, which had been diminished due to 6-OHDA, except for GluR2 levels. These findings provide insight into the mechanisms by which central NPS administration enhances cognitive functions in an experimental model of PD, highlighting its potential therapeutic benefits for addressing cognitive deficits in PD.

Endoport-Assisted Endoscopic Technique for Evacuating Severe Intraventricular Hemorrhage with Cast Third Ventricle Hematoma in an Underwater Field: A Technical Note

ObjectiveThe authors describe a two-stage strategy utilizing the endoport-assisted endoscopic technique for the evacuation of severe intraventricular hemorrhage (IVH) with a cast third ventricle, and discuss potential pitfalls in the implementation of this method in clinical practice. MethodsPatients with severe IVH (Graeb score > 6) and a cast third ventricle who present to our center from 2021 to 2023 were treated in two-stage surgical strategy utilizing the endoport-assisted endoscopic technique. ResultsA total of 9 patients with mean age of 55 years were included in the study. The preoperative mean Graeb score was 9, and postoperative mean Graeb score was 3, with a 72% evacuation rate for the entire ventricles. The median duration for EVD drainage was observed to be 6 days. In terms of 90-day modified Rankin Scale (mRS) scores, a favorable outcome (mRS 1–3) was demonstrated in 78% of the patients, while the remaining 22% presented with a poor outcome (mRS 4–6). There were no complications related to the surgery itself in any of the reported cases. ConclusionThe endoport-assisted two-stage endoscopic technique marks a significant advancement in treating severeIVH with a cast third ventricle. By combining dry and underwater approaches, it provides an innovative solution for effectively and safely clearing hematomas in both lateral and third ventricles. This technique addresses the crucial need for early cerebrospinal fluid circulation restoration, potentially improving outcomes for patients with these complex cases.

Hearing Function Moderates Age-Related Differences in Brain Morphometry in the HCP Aging Cohort.

There are well-established relationships between aging and neurodegenerative changes, and between aging and hearing loss. The goal of this study was to determine how structural brain aging is influenced by hearing loss. Human Connectome Project Aging data were analyzed, including T1-weighted Magnetic Resonance Imaging (MRI) and Words in noise (WIN) thresholds (n = 623). Freesurfer extracted gray and white matter volume, and cortical thickness, area, and curvature. Linear regression models targeted (1) interactions between age and WIN threshold and (2) correlations with WIN threshold adjusted for age, both corrected for false discovery rate (pFDR < 0.05). WIN threshold moderated age-related increase in volume in bilateral inferior lateral ventricles, with a higher threshold associated with increased age-related ventricle expansion. Age-related differences in the occipital cortex also increased with higher WIN thresholds. When controlling for age, high WIN threshold was correlated with reduced cortical thickness in Heschl's gyrus, calcarine sulcus, and other sensory regions, and reduced temporal lobe white matter. Older volunteers with poorer hearing and cognitive scores had the lowest volume in left parahippocampal white matter. These results suggest that better hearing is associated with reduced age-related differences in medial temporal lobe, while better hearing at any age is associated with greater cortical tissue in auditory and other sensory regions. Future longitudinal studies are needed to assess the causal nature of these relationships, but these results indicate interventions that preserve or protect hearing function may combat some neurodegenerative changes in aging.