Addition of eptifibatide and manual thrombus aspiration to ticagrelor does not improve long-term survival after STEMI treated with primary PCI.

Background: Current guidelines recommend that glycoprotein IIb/IIIa inhibitor (GPI) and manual aspiration thrombectomy should not be routinely used in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI), although there is a lack of dedicated studies. The aim of this study was to examine the impact of combined usage of a potent P2Y12 inhibitor, GPI, and manual aspiration thrombectomy on long-term survival after STEMI. Methods: All STEMI patients treated by pPCI in a tertiary center who have been included prospectively in the local PCI registry between January 2016 and December 2022 were analyzed in this study. Patients were excluded if they required oral anticoagulation or bridging between clopidogrel or ticagrelor during hospitalization. Results: A total of 1,210 patients were included in the present study, with a median follow-up of 2.78 (1.00-4.88) years. Ticagrelor significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.27 (0.21-0.34), p < 0.0001 and HR = 0.23 (0.17-0.30), p < 0.0001, respectively]. Eptifibatide significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.72 (0.57-0.92), p = 0.002, and HR = 0.68 (0.52-0.89), p = 0.001, respectively]. Manual thrombus aspiration had no significant effect on both all-cause and cardiovascular-cause mortality. In multivariate Cox regression, all-cause mortality was reduced by ticagrelor, while eptifibatide or manual thrombus aspiration had no significant effect. However, cardiovascular-cause mortality was reduced by both ticagrelor and eptifibatide, while manual thrombus aspiration had no significant effect. Conclusion: Ticagrelor consistently reduced cardiovascular and all-cause mortality, while eptifibatide reduced only cardiovascular mortality. Manual thrombus aspiration provided no long-term benefit. Our findings support the current guideline recommendation that GPI and manual aspiration thrombectomy should not be routinely used in treatment of STEMI with pPCI.

Annotated dataset for training deep learning models to detect astrocytes in human brain tissue.

Astrocytes, a type of glial cell, significantly influence neuronal function, with variations in morphology and density linked to neurological disorders. Traditional methods for their accurate detection and density measurement are laborious and unsuited for large-scale operations. We introduce a dataset from human brain tissues stained with aldehyde dehydrogenase 1 family member L1 (ALDH1L1) and glial fibrillary acidic protein (GFAP). The digital whole slide images of these tissues were partitioned into 8730 patches of 500 × 500 pixels, comprising 2323 ALDH1L1 and 4714 GFAP patches at a pixel size of 0.5019/pixel, furthermore 1382 ADHD1L1 and 311 GFAP patches at 0.3557/pixel. Sourced from 16 slides and 8 patients our dataset promotes the development of tools for glial cell detection and quantification, offering insights into their density distribution in various brain areas, thereby broadening neuropathological study horizons. These samples hold value for automating detection methods, including deep learning. Derived from human samples, our dataset provides a platform for exploring astrocyte functionality, potentially guiding new diagnostic and treatment strategies for neurological disorders.

Early cellular and synaptic changes in dopaminoceptive forebrain regions of juvenile mice following gestational exposure to valproate.

Gestational exposure of mice to valproic acid (VPA) is one currently used experimental model for the investigation of typical failure symptoms associated with autism spectrum disorder (ASD). In the present study we hypothesized that the reduction of dopaminergic source neurons of the VTA, followed by perturbed growth of the mesotelencephalic dopamine pathway (MT), should also modify pattern formation in the dopaminoceptive target regions (particularly its mesoaccumbens/mesolimbic portion). Here, we investigated VPA-evoked cellular morphological (apoptosis-frequency detected by Caspase-3, abundance of Ca-binding proteins, CaBP), as well as synaptic proteomic (western blotting) changes, in selected dopaminoceptive subpallial, as compared to pallial, regions of mice, born to mothers treated with 500 mg/kg VPA on day 13.5 of pregnancy. We observed a surge of apoptosis on VPA treatment in nearly all investigated subpallial and pallial regions; with a non-significant trend of similar increase the nucleus accumbens (NAc) at P7, the age at which the MT pathway reduction has been reported (also supplemented by current findings). Of the CaBPs, calretinin (CR) expression was decreased in pallial regions, most prominently in retrosplenial cortex, but not in the subpallium of P7 mice. Calbindin-D 28K (CB) was selectively reduced in the caudate-putamen (CPu) of VPA exposed animals at P7 but no longer at P60, pointing to a potency of repairment. The VPA-associated overall increase in apoptosis at P7 did not correlate with the abundance and distribution of CaBPs, except in CPu, in which the marked drop of CB was negatively correlated with increased apoptosis. Abundance of parvalbumin (PV) at P60 showed no significant response to VPA treatment in any of the observed regions we did not find colocalization of apoptotic (Casp3+) cells with CaBP-immunoreactive neurons. The proteomic findings suggest reduction of tyrosine hydroxylase in the crude synaptosome fraction of NAc, but not in the CPu, without simultaneous decrease of the synaptic protein, synaptophysin, indicating selective impairment of dopaminergic synapses. The morpho-functional changes found in forebrain regions of VPA-exposed mice may signify dendritic and synaptic reorganization in dopaminergic target regions, with potential translational value to similar impairments in the pathogenesis of human ASD.

Upper cortical layer-driven network impairment in schizophrenia.

Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.

The spatiotemporal dynamics of microglia across the human lifespan.

Microglia, the brain's resident macrophages, shape neural development and are key neuroimmune hubs in the pathological signatures of neurodevelopmental disorders. Despite the importance of microglia, their development has not been carefully examined in the human brain, and most of our knowledge derives from rodents. We aimed to address this gap in knowledge by establishing an extensive collection of 97 post-mortem tissues in order to enable quantitative, sex-matched, detailed analysis of microglia across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing waves in microglial density across gestation, infancy, and childhood, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNA-seq and single-cell RNA-seq datasets. This study provides a detailed insight into the spatiotemporal dynamics of microglia across the human lifespan and serves as a foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.

Prediction of 3-year all-cause and cardiovascular cause mortality in a prospective percutaneous coronary intervention registry: Machine learning model outperforms conventional clinical risk scores.

BACKGROUND AND AIMS: Machine learning (ML) models have been proposed as a prognostic clinical tool and superiority over clinical risk scores is yet to be established. Our aim was to analyse the performance of predicting 3-year all-cause- and cardiovascular cause mortality using ML techniques and compare it with clinical scores in a percutaneous coronary intervention (PCI) population. METHODS: An all-comers patient population treated by PCI in a tertiary cardiovascular centre that have been included prospectively in the local registry between January 2016-December 2017 was analysed. The ML model was trained to predict 3-year mortality and prediction performance was compared with that of GRACE, ACEF, SYNTAX II 2020 and TIMI scores. RESULTS: A total number of 2242 patients were included with 12.1% and 14.9% 3-year cardiovascular and -all-cause mortality, respectively. The area under receiver operator characteristic curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.886 vs. 0.797, 0.792, 0.757 and 0.696 for 3-year cardiovascular- and 0.854 vs. 0.762, 0.764, 0.730 and 0.691 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). Similarly, the area under precision-recall curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.729 vs. 0.474, 0.469, 0.365 and 0.389 for 3-year cardiovascular- and 0.718 vs. 0.483, 0.466, 0.388 and 0.395 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). CONCLUSION: The ML model was superior in predicting 3-year cardiovascular- and all-cause mortality when compared to clinical scores in a prospective PCI registry.

Evidence for Decreased Density of Calretinin-Immunopositive Neurons in the Caudate Nucleus in Patients With Schizophrenia.

Schizophrenia (SCH) and autism spectrum disorder (ASD) share several common aetiological and symptomatic features suggesting they may be included in a common spectrum. For example, recent results suggest that excitatory/inhibitory imbalance is relevant in the etiology of SCH and ASD. Numerous studies have investigated this imbalance in regions like the ventromedial and dorsolateral prefrontal cortex (DLPFC). However, relatively little is known about neuroanatomical changes that could reduce inhibition in subcortical structures, such as the caudate nucleus (CN), in neuropsychiatric disorders. We recently showed a significant decrease in calretinin-immunopositive (CR-ip) interneuronal density in the CN of patients with ASD without significant change in the density of neuropeptide Y-immunopositive (NPY-ip) neurons. These subtypes together constitute more than 50% of caudate interneurons and are likely necessary for maintaining excitatory/inhibitory balance. Consequently, and since SCH and ASD share characteristic features, here we tested the hypothesis, that the density of CR-ip neurons in the CN is decreased in patients with SCH. We used immunohistochemistry and qPCR for CR and NPY in six patients with schizophrenia and six control subjects. As expected, small, medium and large CR-ip interneurons were detected in the CN. We found a 38% decrease in the density of all CR-ip interneurons (P < 0.01) that was driven by the loss of the small CR-ip interneurons (P < 0.01) in patients with SCH. The densities of the large CR-ip and of the NPY-ip interneurons were not significantly altered. The lower density detected could have been due to inflammation-induced degeneration. However, the state of microglial activation assessed by quantification of ionized calcium-binding adapter molecule 1 (Iba1)- and transmembrane protein 119 (TMEM119)-immunopositive cells showed no significant difference between patients with SCH and controls. Our results warrant further studies focussing on the role of CR-ip neurons and on the striatum being a possible hub for information selection and regulation of associative cortical fields whose function have been altered in SCH.

Author Correction: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19869-5.

Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis.

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.

Renal dysfunction is associated with lower incidence of positive fractional flow reserve values in patients with severe hypertension.

BACKGROUND: Renal dysfunction, an important predictor of cardiovascular mortality, is paradoxically associated with a lower incidence of positive coronary fractional flow reserve (FFR) values, possibly due to renal disease-associated myocardial microvascular dysfunction. It is unknown if this relationship is influenced by arterial hypertension, a condition strongly associated with renal- and microvascular dysfunction. METHODS: The incidence of positive (<0.81) FFR values was retrospectively evaluated in consecutive patients with intermediate severity coronary artery lesions that were either associating or not associating renal dysfunction (creatinine clearance, CrCl <90 mL/min/1.73 m2), and had mild/moderate or severe arterial hypertension (treated by <3 or ≥3 different drugs). RESULTS: Positive FFR values were found in 49.5% of the 109 included patients, with a significantly lower incidence in those with renal dysfunction: 23 vs. 31 cases (39.7% vs. 60.8%, P=0.03). However, uni- and multivariate subpopulation analysis evidenced that renal dysfunction was a significant independent predictor of fewer positive FFR results only in severely hypertensive patients (univariate P values for mild/moderate and severe hypertension: 0.80 and <0.01, respectively; multivariate P in severely hypertensive patients: 0.04). This categorization significantly restricted the number of borderline FFR results (0.75-0.80) where measurement interpretation could be challenging because of renal dysfunction (from 13.8% to 4.6% of the whole study population, P=0.03). CONCLUSIONS: In the current study renal dysfunction was independently associated with a significantly higher incidence of negative FFR results in patients with intermediate severity coronary artery lesions only in the presence of severe arterial hypertension. This observation should be confirmed by large-scale prospective clinical trials.

Single-nucleus RNA-seq identifies Huntington disease astrocyte states.

Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated glial fibrillary acidic protein (GFAP) and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different "states", defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte "reactions" to the disease.

Galectin-3 modulates postnatal subventricular zone gliogenesis.

Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.

Neuroserpin expression during human brain development and in adult brain revealed by immunohistochemistry and single cell RNA sequencing.

Neuroserpin is a serine-protease inhibitor mainly expressed in the CNS and involved in the inhibition of the proteolytic cascade. Animal models confirmed its neuroprotective role in perinatal hypoxia-ischaemia and adult stroke. Although neuroserpin may be a potential therapeutic target in the treatment of the aforementioned conditions, there is still no information in the literature on its distribution during human brain development. The present study provides a detailed description of the changing spatiotemporal patterns of neuroserpin focusing on physiological human brain development. Five stages were distinguished within our examined age range which spanned from the 7th gestational week until adulthood. In particular, subplate and deep cortical plate neurons were identified as the main sources of neuroserpin production between the 25th gestational week and the first postnatal month. Our immunohistochemical findings were substantiated by single cell RNA sequencing data showing specific neuronal and glial cell types expressing neuroserpin. The characterization of neuroserpin expression during physiological human brain development is essential for forthcoming studies which will explore its involvement in pathological conditions, such as perinatal hypoxia-ischaemia and adult stroke in human.

The First Postlesion Minutes: An In Vivo Study of Extravasation and Perivascular Astrocytes Following Cerebral Lesions in Various Experimental Mouse Models.

The immediate alterations following lesions cannot be investigated by using fixed tissues. Here, we employed two-photon microscopy to study the alterations to the permeability of blood-brain barrier and to glio-vascular connections in vivo during the first minutes following cortical lesions in mice. Four models were used: (1) cryogenic lesion, (2) photodisruption using laser pulses, (3) photothrombosis, and (4) bilateral carotid ligation. Sulforhodamine101 was used for supravital labeling of astrocytes and dextran-bound fluorescein isothiocyanate for the assessment of extravasation. Transgenic mice, in which the endothelium and astrocytes expressed a yellow fluorescent protein, were also used. Astrocytic labeling in vivo was verified with postmortem immunostaining against glial fibrillary acidic protein (GFAP). Summary of results: (1) the glio-vascular connections were stable in the intact brain with no sign of spontaneous dynamic attachment/detachment of glial end-feet; (2) only direct vascular damage (photodisruption or cryogenic) resulted in prompt extravasation; (3) even direct damage failed to provoke a prompt astroglial response. In conclusion, the results indicate that a detachment of the astrocytic end-feet does not precede the breakdown of blood-brain barrier following lesions. Whereas vasogenic edema develops immediately after the lesions, this is not the case with cytotoxic edemas. Time-lapse recordings and three-dimensional reconstructions are presented as supplemental materials.

Disappearance of cerebrovascular laminin immunoreactivity as related to the maturation of astroglia in rat brain.

The present paper provides novel findings on the temporo-spatial correlation of perivascular laminin immunoreactivity with the early postnatal astrocyte development. The cerebrovascular laminin immunoreactivity gradually disappears during development. The fusion of the glial and vascular basal laminae during development makes the laminin epitopes inaccessible for antibody molecules (Krum et al., 1991, Exp Neurol 111:151). The fusion is supposed to correlate with the maturation of the glio-vascular connections. Glial development was followed by immunostaining for GFAP (glial fibrillary acidic protein), S100 protein, glutamine synthetase as glial markers and for nestin to visualize the immature glial structures. Our investigation focused on the period from postnatal day (P)2 to P16, on the dorso-parietal pallium. In the wall of the telencephalon the laminin immunoreactivity disappeared between P5 and P10; in subcortical structures it persisted to P12 or even to P16. Its disappearance overlapped the period when GFAP-immunopositive astrocytes were taking the place of radial glia. Despite the parallel time courses, however, the spatial patterns of the two processes were just the opposite: disappearance of the laminin immunoreactivity progressed from the middle zone whereas the appearance of GFAP from the pial surface and the corpus callosum. Rather, the regression of the vascular laminin immunoreactivity followed the progression of the immunoreactivities of glutamine synthetase and S100 protein. Therefore, the regression really correlates with a 'maturation' of astrocytes which, however, affects other astrocyte functions rather than cytoskeleton.

Appearance of ß-dystroglycan precedes the formation of glio-vascular end-feet in developing rat brain.

Dystroglycan has an important role in binding of perivascular glial end-feet tothe basal lamina. Its ß-subunit is localized in the glial end-feet. The investigation period lasted from E(embryonic day)12 to E20. Laminin and ß-dystroglycan were detected by immunohistochemistry, the glial localization of the latter one was supported  by electron microscopy. The immatureglial structures were visualized by the immunostaining of nestin. The ß-dystroglycan immunoreactivity appeared at E16 following the laminin of basal lamina but preceding the perivascular processes of radial glia (E18) and astrocyte-like cells (E20). It occurred in cell bodies which attached to the vessels directly but not with vascular processes and end-feet. The presence of ß-dystroglycan in such immature cells may promote their differentiation to perivascular astrocytes and influence the formation of the glio-vascular processes.

Calretinin interneuron density in the caudate nucleus is lower in autism spectrum disorder.

Autism spectrum disorder is a debilitating condition with possible neurodevelopmental origins but unknown neuroanatomical correlates. Whereas investigators have paid much attention to the cerebral cortex, few studies have detailed the basal ganglia in autism. The caudate nucleus may be involved in the repetitive movements and limbic changes of autism. We used immunohistochemistry for calretinin and neuropeptide Y in 24 age- and gender-matched patients with autism spectrum disorder and control subjects ranging in age from 13 to 69 years. Patients with autism had a 35% lower density of calretinin+ interneurons in the caudate that was driven by loss of small calretinin+ neurons. This was not caused by altered size of the caudate, as its cross-sectional surface areas were similar between diagnostic groups. Controls exhibited an age-dependent increase in the density of medium and large calretinin+ neurons, whereas subjects with autism did not. Diagnostic groups did not differ regarding ionized calcium-binding adapter molecule 1+ immunoreactivity for microglia, suggesting chronic inflammation did not cause the decreased calretinin+ density. There was no statistically significant difference in the density of neuropeptide Y+ neurons between subjects with autism and controls. The decreased calretinin+ density may disrupt the excitation/inhibition balance in the caudate leading to dysfunctional corticostriatal circuits. The description of such changes in autism spectrum disorder may clarify pathomechanisms and thereby help identify targets for drug intervention and novel therapeutic strategies.

Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche.

Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI.

Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis.

Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3(-/-) mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3(-/-) mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3(-/-) mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.

Phases of intermediate filament composition in Bergmann glia following cerebellar injury in adult rat.

In contrast to other astroglial populations, Bergmann glia (BG) form a strictly arranged system where each cell contacts the pia, with an architecture and function resembling that of immature radial glia. As a consequence, a post-lesion glial reaction is expected to differ from that observed in other parts of the brain. The present study describes the characteristic phases of intermediate filament protein formation during the different stages of BG response following injury and compares them with reactive glial patterns of other brain areas and patterns of glial development. The progress of Bergmann glial repair shares similar features with glial development. Following injury, BG developed nestin immunopositivity; then, colocalization of nestin and GFAP was observed. Finally, exclusively GFAP-immunopositive BG were restituted, denser, and thicker than before. The changes of intermediate filament composition appeared at first at the proximal and distal ends of BG fibers, i.e., at the perikaryal "root" and in the pial endfeet. No astrocytic invasion was present in the molecular layer, nor any distinct rearrangement of BG. These results demonstrate the role of the resident glia in glial reactions and refer to the priority of gliomeningeal connections.