Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
Primordial Follicle Response to Two Methods of Ovarian Cortex Retrieval and Vitrification: A Pilot Study
Cureus 2025 17(5): e84918
Rebeca Chávez-Genaro 1 , Gabriel Anesetti 1 , Lorena Bonjour 1 , Clara Fernández 1 , Agustina Toledo 1 , Karina Hernández 1 , Natalibeth Barrera 2 , Lidia Cantú 2 , Dana Kimelman 3
1. Histology and Embryology, Universidad de la República, Montevideo, URY 2. Embryology, Centro de Esterilidad Montevideo, Montevideo, URY 3. Gynecology, Centro Hospitalario Pereira Rossell, Administración de los Servicios de Salud del Estado, Montevideo, URY
DOI: 10.7759/cureus.84918
PMID: 40575194
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40575194
Texto completo: https://www.cureus.com/articles/367394#!/
Abstract:
Cryopreservation and transplantation of ovarian cortical tissue are novel techniques to preserve fertility in young patients undergoing gonadotoxic treatments that may affect fertility. Vitrification has demonstrated growing success in restoring ovarian function and achieving pregnancy post-grafting. It helps maintain communication between follicles and interstitial tissue, which is essential for follicular growth. This study compares two ovarian cortex dissection techniques (strips and layers) using an ovine animal model. The results indicate that manipulation of the ovarian cortex affects primordial follicle activation and stromal tissue during vitrification, potentially compromising oocyte viability and reproductive potential. Additionally, the distribution of primordial follicles in ovarian tissue varies, influencing transplantation efficiency. Both dissection methods increase follicle activation, suggesting that mechanical manipulation impacts outcomes. These findings underscore the need to optimize tissue processing to enhance fertility preservation, particularly by understanding the roles of the stromal and extracellular matrix (ECM) in maintaining follicle dormancy and viability post-vitrification and reimplantation.
Adult neurogenesis in the Uruguayan teleost species Austrolebias charrua and Gymnotus omarorum
Neuroscience 2025 May 7:573:143-153
María E Castelló 1 , Valentina Olivera-Pasilio 2 , Juan Carlos Rosillo 3 , Anabel S Fernández 4
1 Laboratorio de Desarrollo Y Evolución Neural, Departamento de Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay. Electronic address: mcastello@iibce.edu.uy. 2 Laboratorio de Desarrollo Y Evolución Neural, Departamento de Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay; Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: valentina.oliverapasilio@northwestern.edu. 3 Laboratorio de Neurobiología Comparada, Departamento Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Uruguay; Departamento de Histología Y Embriología, Facultad de Medicina, UdelaR. Avda. General Flores 2125 11800 Montevideo, Uruguay; Departamento de Neurobiología Y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Avenida. Italia 3318 11600 Montevideo, Uruguay. Electronic address: jrosillo@iibce.edu.uy. 4 Laboratorio de Neurobiología Comparada, Departamento Neurociencias Integrativas Y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE-MEC), Uruguay; Laboratorio de Neurociencias, Instituto de Biología, Facultad de Ciencias, UdelaR, Iguá 4225 11400 Montevideo, Uruguay. Electronic address: afernandez@iibce.edu.uy.
DOI: 10.1016/j.neuroscience.2025.03.027
PMID: 40101892
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40101892
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(25)00229-5
Abstract:
Neurogenesis -the process by which new neurons are generated in the brain- is critical for nervous system development and plasticity. Adult neurogenesis underlies growth, repair, and adaptation to environmental changes. Vertebrates differ in their neurogenic and regenerative capacity, being particularly prominent in teleost as adult neurogenesis occurs throughout the rostral-caudal brain axis. This review examines adult proliferation and neurogenesis in the autochthonous Uruguayan teleost Austrolebias charrua and Gymnotus omarorum. A. charrua are annual fishes that live in temporary freshwater pools that dry up in the summer. The luminosity of the puddles varies greatly, and both vision and olfaction are crucial for the survival of this species. G. omarorum inhabits freshwater lagoons and rivers beneath dense masses of floating plants and have nocturnal habits. They rely on the electrosensory modality to navigate and communicate with conspecifics. These differences in habitats and predominant sensory modalities are reflected in the distinct brain morphotypes of G. omarorum and A. charrua. While G. omarorum is characterized by the hypertrophy of rhombencephalic cerebellum and electrosensory lateral line lobe, A. charrua has a well-developed olfactory bulb, mesencephalic tectum opticum, and torus longitudinalis. Accordingly, these regions have notorious neurogenic activity. Differences in neuroanatomy and distribution of neurogenesis in the brains of both species are discussed considering their life cycle and lifestyle. The comparison of these results with those reported in other teleost and vertebrates contributes to the understanding of the key role of neurogenesis in brain plasticity and evolution.
Taking flight, the use of Drosophila melanogaster for neuroscience research in Uruguay
Neuroscience 2025 May 7:573:104-119
Gonzalo Budelli 1 , María José Ferreiro 2 , Carmen Bolatto 3
1 Unidad Académica de Biofísica, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. Electronic address: gbudelli@fmed.edu.uy. 2 Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Ministerio de Educación y Cultura (MEC), Montevideo, Uruguay. 3 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay; Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Ministerio de Educación y Cultura (MEC), Montevideo, Uruguay.
DOI: 10.1016/j.neuroscience.2025.03.006
PMID: 40058485
Pubmed: https://pubmed.ncbi.nlm.nih.gov/40058485
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(25)00193-9
Abstract:
The Sociedad de Neurociencias del Uruguay is celebrating its 30th anniversary, sustained by more than a century of neuroscience research in the country. During this time, different approaches and experimental organisms have been incorporated to study diverse aspects of neurobiology. One of these experimental animals, successfully used in a variety of biological fields, is the fruit fly Drosophila melanogaster. Although Drosophila has been a model organism for neuroscience research worldwide for many decades, its use in Uruguay for that purpose is relatively new and just taking flight. In this special issue article, we will describe some of the research lines that are currently using Drosophila for neuroscience studies, questioning a wide range of issues including thermoreception, neurodegenerative diseases such as Parkinson's, screening of bioactive compounds with a neuroprotective effect, and gene/protein function during development of the nervous system. The consolidation of these research lines has been achieved due to unique features of D. melanogaster as an experimental model. We will review the advantages of using Drosophila to study neurobiology and describe some of its useful genetic tools. Advantages such as having powerful genetics, highly conserved disease pathways, a complete connectome, very low comparative costs, easy maintenance, and the support of a collaborative community allowing access to a vast toolkit, all make D. melanogaster an ideal model organism for neuroscientists in countries with low levels of investment in research and development. This review focuses on the strengths and description of useful techniques to study neurobiology using Drosophila, from the perspective of a Latin-American experience.
Neurovascular unit impairment in iron deficiency anemia
Neuroscience 2025 Feb 16:567:56-66
Eugenia Isasi 1 , Silvia Olivera-Bravo 2
1 Unidad Académica de Histología y Embriología, Facultad de Medicina, UdelaR, Montevideo, Uruguay; Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. 2 Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. Electronic address: solivera@iibce.edu.uy.
DOI: 10.1016/j.neuroscience.2024.12.050
PMID: 39733822
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39733822
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(24)00757-7
Abstract:
Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments. The neurovascular unit (NVU) plays an important role in iron transport within the CNS as well as in the blood brain-barrier (BBB) formation and maturation, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. In animal models of IDA, significant changes have been observed at the capillary level, including alterations in iron transport, vasculogenesis, astrocyte endfeet, and pericytes. Despite these findings, the role of the NVU in IDA remains poorly understood. This review summarizes the potential effects of ID/IDA on brain development, myelination and neuronal function and discusses the role of NVU cells in iron metabolism, BBB, vasculogenesis/angiogenesis, neurovascular coupling and metabolic waste clearance. Furthermore, it emphasizes the need to view the NVU as a whole and as a potential target for ID/IDA. However, it remains unclear to what extent NVU alterations contribute to neuronal dysfunction, myelination abnormalities, and synaptic disturbances described in IDA.
Mitochondria and astrocyte reactivity: Key mechanism behind neuronal injury
Neuroscience 2025 Feb 16:567:227-234
Patricia Cassina 1 , Ernesto Miquel 2 , Laura Martínez-Palma 2 , Adriana Cassina 3
1 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: pcassina@fmed.edu.uy. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3 Departemento de Bioquímica and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1016/j.neuroscience.2024.12.058
PMID: 39788313
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39788313
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(24)00765-6
Abstract:
In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system. Although astrocytes are typically considered to exhibit low mitochondrial respiratory chain activity, they possess a noteworthy mitochondrial network. Interestingly, both the morphology and activity of these organelles change following glial reactivity. Despite receiving less attention compared to studies on neuronal mitochondria, recent studies indicate that mitochondria play a crucial role in driving the transition of astrocytes from a quiescent to a reactive state in various neurological disorders. Notably, stimulating mitochondria in astrocytes has been shown to reduce damage associated with the neurodegenerative disease amyotrophic lateral sclerosis. Here, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage. In this review, we focus on studies supporting the emerging paradigm that metabolic reprogramming occurs in astrocytes following damage, which is associated with their phenotypic shift to a new functional state that significantly influences the progression of pathology. Thus, exploring mitochondrial activity and metabolic reprogramming within glial cells may provide valuable insights for developing innovative therapeutic approaches to mitigate neuronal damage.
2025_Cassina_rev_Mitochondria and astrocyte reactivity-Key mechanism behind neuronal injury.pdf
Müller glia in short-term dark adaptation of the Austrolebias charrua retina: Cell proliferation and cytoarchitecture
Exp Cell Res 2025 Jan 15;444(2):114394
Laura Herrera-Astorga 1 , Stephanie Silva 2 , Inés Berrosteguieta 3 , Juan Carlos Rosillo 4 , Anabel Sonia Fernández 5
1 Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay; Sección Fisiología y Nutrición, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay. Electronic address: lherrera@iibce.edu.uy. 2 Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay. Electronic address: ssilva@fcien.edu.uy. 3 Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay. Electronic address: iberrosteguieta@iibce.edu.uy. 4 Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, 11800, Montevideo, Uruguay. Electronic address: jrosillo@iibce.edu.uy. 5 Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay. Electronic address: afernandez@iibce.edu.uy.
DOI: 10.1016/j.yexcr.2024.114394
PMID: 39722301
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39722301
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(24)00485-3
Abstract:
Fish with unique life cycles offer valuable insights into retinal plasticity, revealing mechanisms of environmental adaptation, cell proliferation, and thus, potentially regeneration. The variability of the environmental factors to which Austrolebias annual fishes are exposed has acted as a strong selective pressure shaping traits such as nervous system plasticity. This has contributed to adaptation to their extreme conditions including the decreased luminosity as ponds dry out. In particular, the retina of A. charrua has been shown to respond to 30 days of decreased luminosity by exacerbating cell proliferation Now, we aimed to determine the cellular component of the retina involved in shorter-term responses. To this end, we performed 5-bromo-2'-deoxyuridine (BrdU) experiments, exposing adult fish to a short period (11 days) of constant darkness. Strikingly, in control conditions, neurogenesis in the inner nuclear and ganglion cell layer in the differentiated retina was detected. In constant darkness, we observed an effect on inner nuclear layer cell proliferation and changes in retinal cytoarchitecture of the retina with cell clusters located in the inner plexiform layer. Additionally, increased BLBP (brain lipid-binding protein) presence was detected in darkness, which has been previously associated with immature and reactivated Müller glia. Thus, our results suggest that the A. charrua retina can respond to environmental changes via rapid activation of progenitor cells in the INL, namely the Müller glia This leads us to hypothesize, that cell proliferation and neurogenesis might contribute to the responses to the functional needs of organisms, potentially playing an adaptive role.
Evaluation of the efficacy and safety of gravitational therapy in a cohort of patients with systemic sclerosis
Reumatol Clin 2024 Nov;20(9):463-469
Luisa Fernanda Servioli 1 , Eugenia Isasi 2 , Alejandra Pérez 3 , Silvia Pouquette 3 , María Eloísa Isasi 3
1 Unidad de Enfermedades Autoinmunes Sistémicas, Hospital Militar, Montevideo, Uruguay. Electronic address: lservioli01@gmail.com. 2 Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Centro de Terapia Gravitacional, Montevideo, Uruguay. 3 Centro de Terapia Gravitacional, Montevideo, Uruguay.
DOI: 10.1016/j.reumae.2024.10.004
PMID: 39487058
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39487058
Texto completo: http://www.elsevier.es/en/linksolver/pdf/pii/S2173-5743(24)00137-0
Abstract:
Background: The exposure to artificial gravity (AG) through human centrifugation is the basis of the treatment called gravity therapy (GT), in which the mechanical stimulation over the vessel wall, induces the synthesis and release of prostacyclin. It has been used for more than four decades in Uruguay in the treatment of different vascular-based pathologies. In patients with systemic sclerosis (SSc) it has shown good benefits and excellent safety profile over the years. However, there is a lack of knowledge in the scientific community about GT and its results.
Brain atlas of the annual Garcialebias charrua fish
Anat Rec (Hoboken) 2024 Oct;307(10):3384-3397.
Maximiliano Torres-Pérez 1 2 , María Laura Herrera 1 , Juan Carlos Rosillo 1 3 , Inés Berrosteguieta 1 , Gabriela Casanova 4 , Silvia Olivera-Bravo 2 , Anabel Sonia Fernández 1 5
1 División Neurociencias, Departamento de Neurociencias Integrativas y Computacionales, Laboratorio de Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. 2 División Neurociencias, Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. 3 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay. 4 Unidad de Microscopía Electrónica, Facultad de Ciencias, Universidad de la República (UdelaR), Montevideo, Uruguay. 5 Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República (UdelaR), Montevideo, Uruguay.
DOI: 10.1002/ar.25432
PMID:
Pubmed: https://pubmed.ncbi.nlm.nih.gov/
Texto completo: https://doi.org/10.1002/ar.25432
Abstract:
Annual fish have become attractive study models for a wide range of disciplines, including neurobiology. These fish have developed different survival strategies. As a result, their nervous system is under considerable selective pressure when facing extreme environmental situations. Fish from the Austrolebias group exhibit rapid neurogenesis in different brain regions, possibly as a result of the demanding conditions of a changing habitat. Knowledge of cerebral histology is essential for detecting ontogenic, anatomical, or cytoarchitectonic changes in the brain during the short lifespan of these fish, such as those reflecting functional adaptive plasticity in different systems, including sensory structures. The generation of an atlas of Garcialebias charrua (previously known as Austrolebias charrua) establishes its anatomical basis as a representative of a large group of fish that share similarities in their way of life. In this work, we present a detailed study of both gross anatomy and microscopic anatomy obtained through serial sections stained with the Nissl technique in three orientations: transverse, horizontal, and parasagittal planes. This atlas includes accurate drawings of the entire adult brain of the male fish Garcialebias charrua, showing dorsal, ventral, and lateral views, including where emergence and origin of cranial nerves. This brain atlas allows us to understand histoarchitecture as well as the location of neural structures that change during adult neurogenesis, enabling comparisons within the genus. Simultaneously, this atlas constitutes a valuable tool for comparing the brains of other fish species with different behaviors and neuroecologies.
Cerebral White Matter Alterations Associated With Oligodendrocyte Vulnerability in Organic Acidurias: Insights in Glutaric Aciduria Type I
Neurotox Res 2024 Jul 4;42(4):33
Eugenia Isasi 1 2 , Moacir Wajner 3 4 , Juliana Avila Duarte 5 , Silvia Olivera-Bravo 6
1 Laboratorio de Neurobiología Celular y Molecular, Unidad Académica de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2 Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. 3 Department of Biochemistry, Instituto de Ciencias Básicas da Saude, Universidade Federal de Río Grande do Sul, Porto Alegre, Brazil. 4 Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 5 Departamento de Medicina Interna, Serviço de Radiología, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 6 Departamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay. solivera@iibce.edu.uy.
DOI: 10.1007/s12640-024-00710-6
PMID: 38963434
Pubmed: https://pubmed.ncbi.nlm.nih.gov/38963434
Texto completo: https://dx.doi.org/10.1007/s12640-024-00710-6
Abstract:
The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.
The complement system in neurodegenerative and inflammatory diseases of the central nervous system
Front Neurol 2024 Jul 3:15:1396520
Luciana Negro-Demontel # 1 2 3 , Adam F Maleki # 1 4 , Daniel S Reich 4 , Claudia Kemper 1
1 National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Complement and Inflammation Research Section (CIRS), Bethesda, MD, United States. 2 Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay. 3 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 4 Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD, United States. # Contributed equally.
DOI: 10.3389/fneur.2024.1396520
PMID: 39022733
Pubmed: https://pubmed.ncbi.nlm.nih.gov/39022733
Texto completo: https://doi.org/10.3389/fneur.2024.1396520
Abstract:
Neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, affect millions of people globally. As aging is a major risk factor for neurodegenerative diseases, the continuous increase in the elderly population across Western societies is also associated with a rising prevalence of these debilitating conditions. The complement system, a crucial component of the innate immune response, has gained increasing attention for its multifaceted involvement in the normal development of the central nervous system (CNS) and the brain but also as a pathogenic driver in several neuroinflammatory disease states. Although complement is generally understood as a liver-derived and blood or interstitial fluid operative system protecting against bloodborne pathogens or threats, recent research, particularly on the role of complement in the healthy and diseased CNS, has demonstrated the importance of locally produced and activated complement components. Here, we provide a succinct overview over the known beneficial and pathological roles of complement in the CNS with focus on local sources of complement, including a discussion on the potential importance of the recently discovered intracellularly active complement system for CNS biology and on infection-triggered neurodegeneration.