Cellular Distribution of C-C Motif Chemokine Ligand 2 Like Immunoreactivities in Frontal Cortex and Corpus Callosum of Normal and Lipopolysaccharide Treated Animal

Background: C-C motif chemokine ligand 2 (CCL2) is reported to be involved in the pathogenesis of various neurological and/or psychiatric diseases. Tissue or cellular expression of CCL2, in normal or pathological condition, may play an essential role in recruiting of monocytes or macrophages into the targeted organs, and be involved in a certain pathogenic mechanism. However, only a few studies focused on tissue and cellular distribution of the CCL2 peptide in the brain’s grey and white matters (GM, WM), and the changes of the GM and WM cellular CCL2 level in septic or endotoxic encephalopathy was not explored. Hence, the CCL2 cellular distribution in the front brain cortex and the corpus callosum (CC) WM was investigated in the present work by using immunofluorescent staining. Results: 1) Normally, CCL2 like immunoreactivity (CCL2-ir) in the CC is significantly higher than the cortex, especially when the measurement includes ependymal layer attached to the CC. 2) Structures surrounding the vasculatures contribute major CCL2-ir positive profiles in both GM and WM, but significantly more in the CC WM, in which they are bilaterally distributed and predominantly located in the lateral CC between the cingulate cortex and the lateral ventricles. 3) Following systemic lipopolysaccharide (LPS), the number of neuron-like CCL2-ir positive cells are increased significantly in the cortex, but not in the CC. 4) More CCL2-ir positive elements are accumulated inside microvasculature like structures in the CC WM, compared to those found in the cortex following systemic LPS. 5) Few macrophage/microglia marker-Iba-1 labeled structures exhibit CCL2-ir in normal cortex and CC, but the co-localization is significantly increased following systemic LPS. 6) Following saline or LPS injection, CCL2-ir and GFAP or Iba-1 double labeled structures are observed within the ependymal layer between the lateral ventricles and the CC. No accumulation of neutrophils was detected.Conclusion: there exist differences in the cellular distribution of the CCL2 peptide in the front brain cortex GM and the subcortical WM - the CC, in both the physiological condition and experimental endotoxemia. Which might cause different pathological change in the GM and WM.

Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability.Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed.Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed.Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year.Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

Continual reelin signaling by the prime neurogenic niche of the adult brain

During development reelin sets the pace of neocortical neurogenesis enabling in turn newborn neurons to migrate, but whether and, if so, how reelin signaling affects the adult neurogenic niches remains uncertain. We show that reelin signaling, resulting in Dab1 phosphorylation, occurs in the ependymal-subependymal zone (EZ/SEZ) of the lateral ventricles where, along with its associated rostral migratory stream (RMS), the highest density of functional ApoER2 accumulates. Mice deficient for reelin, ApoER2 or Dab1 exhibit enlarged ventricles and dysplastic RMS. Moreover, while the conditional ablation of Dab1 in neural progenitor cells (NPCs) enlarges the ventricles and impairs neuroblasts clearance from the SEZ, the transgenic misexpression of reelin in NPCs of reelin-deficient mice normalizes the ventricular lumen and the density of ependymal cilia, ameliorating in turn neuroblasts migration; consistently, intraventricular infusion of reelin reroutes neuroblasts. These results demonstrate that reelin signaling persists sustaining the germinal niche of the lateral ventricles and influencing neuroblasts migration in the adult brain.

Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.

Intraventricular meningiomas: A case series and literature review.

Objective: Intraventricular meningiomas (IVMs) are rare type of meningiomas. Majority of IVMs are located in lateral ventricles. Study Design: Case Series. Setting: Civil Hospital Karachi. Period: January 2013 to January 2018. Material & Methods: 15 patients were assessed with histologically verified IVMs, clinical features, radiological findings, surgical approaches, outcome and literature review. Results: The most common presentations included raised intracranial pressure (66.7%), visual deficits (40%), cognitive changes and dysphasia. All lesions arose in the lateral ventricles. Preoperative diagnosis was confirmed on MRI. Excision was performed using the posterior parietal and parieto-temporal approach for lateral ventricle tumors. Total excision was done in 13 out of 15 patients and two patients with residual tumor underwent stereotactic radiosurgery. Biopsy report showed WHO grade-I lesion in all cases. Postoperative complications included CSF leakage, transient hemiparesis and dysphasia. Glasgow Outcome Score of 5 was found in majority of cases (87%) on follow-up. Conclusion: These results depict that IVMs can be excised completely with minimum postoperative morbidity. However, resection requires planning to avoid eloquent cortical damage.

Asymmetric Lateral Ventricles—A Tale of Two Cases

Asymmetry of the lateral ventricles is not an uncommon finding. On one end, it is a predictor of intracranial pathology, and on the other, it can represent a normal variant. It needs to be appropriately investigated. In this case report, we presented two cases of asymmetric lateral ventricles, their presentation, progression and management.

Morphological Signs of Dystrophy, Regeneration and Hypertrophy of Neurons

Results: Dystrophic changes constitute an extensive group of neuronal disorders and are manifested at the morphological level by deformation of the perikarions and neuropil, wrinkling or swelling of the cell, and changes in the chromatophilia of the cytoplasm. At the electron microscopic level, disorganization of organelles is observed, reflecting gross violations of the vital processes of the neuron. There are several ways to regenerate neurons: intracellular regeneration, restoration of the neuropil, the formation of new neurons (in some parts of the nervous system - the hippocampus, the subventricular layer of the lateral ventricles and olfactory bulbs) and the formation of heterokaryons (fusion of a neuron with an oligodendrocyte). Hypertrophy of neurons may indicate both compensation and the development of a pathological process. To clarify the nature of this phenomenon, it is necessary to conduct an ultramicroscopic study of the organelles of the nerve cell.