[Stress during prenatal and early postnatal period when everything begins]. / Les stress pendant les 1 000 premiers jours de la vie quand tout commence.

Early severe stresses are known to affect the biological and psychological development in childhood. Good and adaptable stress during prenatal and early postnatal period can switch to traumatic during these highly susceptible developmental stages. These different stresses modulate genetic/epigenetic processes and the setting up of connectome during these highly plastic and adaptable time periods. The polyvagal processes control the base of the security/well-being perception of the newborn by the onset of synchronized interactions between the mother/parent/nurse and the baby. These positive adjustments in mirror lead to attachment and social links and to implicit learning processes leading to a balanced emotional and cognitive development.

Title: Les stress pendant les 1 000 premiers jours de la vie quand tout commence. Abstract: Les stress présents pendant les 1 000 premiers jours de vie, période de grande vulnérabilité, peuvent avoir un impact sur la biologie de l'enfant et son psychisme. Qu'ils soient bénéfique, adaptable ou toxique, ces stress modulent des régulations génétiques et épigénétiques ainsi que l'installation du connectome du bébé dans la période de grande plasticité et d'adaptation de ces âges précoces. Les régulations des systèmes polyvagaux forment le socle du ressenti de bien-être du bébé, de sa sécurisation dans des synchronies mère, parents, soignants et nouveau-né. Ces régulations positives, en miroir, mènent à l'attachement et aux liens sociaux, aux apprentissages implicites et aux développements émotif, cognitif et comportemental harmonieux.

[Anatomy and physiology of traumatic stress]. / Anatomie et physiologie du stress traumatique.

Facing a more or less intrusive stress, some individuals can cope as they are more resilient, while others get traumatized and further develop a Post Traumatic Stress Disorder (PTSD). Individuals are not equal facing traumatic stress for genetic/epigenetic or personal reasons. This review analyzes from animal models to human, the neurobiological changes detected when the stress switch from adaptable in everyday life to pathological leading to PTSD. Fear memories lead to the disruption of the anatomy/morphology of emotional-memory networks centered on the amygaloïd complex and hippocampal hub associated with the homeostatic unbalance of the body-brain exchanges of molecules such as hormones, neuromodulators or peptides. Persistent fear memories are hardly handled by the frontal ability for decision making towards action. But these fear memories can be revisited by different therapies recruiting cerebral plasticity and resilience. Current understanding of PTSD allowed to develop a series of efficient treatments associating precise medicine to diverse body-mind therapies.

TITLE: Anatomie et physiologie du stress traumatique. ABSTRACT: Le stress prend des formes très variées, allant de bénéfique, bénigne à traumatique. Chaque individu avec son patrimoine génétique et épigénétique et ses mémoires émotionnelles singulières réagit différemment face au stress. L'effet du stress aigu ou chronique est objectivé par l'élévation d'hormones, comme le cortisol, et d'autres molécules circulantes, évoluant au cours du temps. Après avoir décrit les comportements face au danger, nous exposons dans cette Synthèse, les différentes régulations anatomiques et physiologiques susceptibles de varier lors du passage d'un stress adaptable à un stress traumatique (et de ses mémoires), pouvant entraîner l'installation de troubles de stress post-traumatique (TSPT). Des traitements médicamenteux et des thérapies novatrices permettent d'initier l'extinction des mémoires associées à la peur et d'améliorer la prise en charge des troubles de stress post-traumatiques.

Human Motor Thalamus Reconstructed in 3D from Continuous Sagittal Sections with Identified Subcortical Afferent Territories.

Classification and delineation of the motor-related nuclei in the human thalamus have been the focus of numerous discussions for a long time. Difficulties in finding consensus have for the most part been caused by paucity of direct experimental data on connections of individual nuclear entities. Kultas-Ilinsky et al. (2011) showed that distribution of glutamic acid decarboxylase isoform 65 (GAD65), the enzyme that synthesizes inhibitory neurotransmitter γ-aminobutyric acid, is a reliable marker that allows to delineate connectionally distinct nuclei in the human motor thalamus, namely the territories innervated by nigral, pallidal, and cerebellar afferents. We compared those immunocytochemical staining patterns with underlying cytoarchitecture and used the latter to outline the three afferent territories in a continuous series of sagittal Nissl-stained sections of the human thalamus. The 3D volume reconstructed from the outlines was placed in the Talairach stereotactic coordinate system relative to the intercommissural line and sectioned in three stereotactic planes to produce color-coded nuclear maps. This 3D coordinate-based atlas was coregistered to the Montreal Neurological Institute (MNI-152) space. The current report proposes a simplified nomenclature of the motor-related thalamic nuclei, presents images of selected histological sections and stereotactic maps illustrating topographic relationships of these nuclei as well as their relationship with adjacent somatosensory afferent region. The data are useful in different applications such as functional MRI and diffusion tractography. The 3D dataset is publicly available under an open license and can also be applicable in clinical interventions in the thalamus.

Hippocampal Radial Glial Subtypes and Their Neurogenic Potential in Human Fetuses and Healthy and Alzheimer's Disease Adults.

Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX+ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin+ and/or GFAPδ+ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult.

GluNs Detection and Functions in Microglial Cells.

Proving endogenous GluN presence and functions in microglia require complementary steps to demonstrate (1) that GluN genes are transcripted and translated, (2) their cellular localization, (3) that the GluN are functional, and (4) the role of the functional GluN. The complete demonstration is performed by using mRNA detection technics, western blots, immunofluorescence, electrophysiology, calcium imaging, morphology studies, multiplex immunoassay together with conditional microglial Knock-Out mice and brain lesion models.

Dynamic Expression Patterns of Progenitor and Neuron Layer Markers in the Developing Human Dentate Gyrus and Fimbria.

The molecular mechanisms that orchestrate the development of the human dentate gyrus are not known. In this study, we characterized the formation of human dentate and fimbrial progenitors and postmitotic neurons from 9 gestational weeks (GW9) to GW25. PAX6+ progenitor cells remained proliferative until GW16 in the dentate ventricular zone. By GW11, the secondary dentate matrix had developed in the intermediate zone, surrounding the dentate anlage and streaming toward the subpial layer. This secondary matrix contained proliferating PAX6+ and/or TBR2+ progenitors. In parallel, SOX2+ and PAX6+ fimbrial cells were detected approaching the dentate anlage, representing a possible source of extra-dentate progenitors. By GW16, when the granule cell layer could be delineated, a hilar matrix containing PAX6+ and some TBR2+ progenitors had become identifiable. By GW25, when the 2 limbs of the granule cell layer had formed, the secondary dentate matrix was reduced to a pool of progenitors at the fimbrio-dentate junction. Although human dentate development recapitulates key steps previously described in rodents, differences seemed to emerge in neuron layer markers expression. Further studies are necessary to better elucidate their role in dentate formation and connectivity.

Dynamic Expression Patterns of Progenitor and Pyramidal Neuron Layer Markers in the Developing Human Hippocampus.

The molecular mechanisms underlying the formation of hippocampus are unknown in humans. To improve our knowledge of molecules that potentially regulate pyramidal neurogenesis and layering in various hippocampal fields, we investigated the expression of progenitor markers and cell fate molecules from gestational week (GW) 9 to GW 20. At GW 9, the progenitor cell compartment of the hippocampal formation mainly consisted of PAX6(+) cells in the ventricular zone. Between GW 9 and 11, a second germinal area, the subventricular zone (SVZ), was formed, as shown by TBR2 labeling. Postmitotic markers (TBR1, CTIP2, SATB2, and CUX1) might reflect the inside-out layering of the plate from GW 11 onwards. TBR1(+) neurons appeared in the deep plate, whereas CTIP2(+), SATB2(+), and CUX1(+) neurons occupied the upper layers. From GW 16, differences in layer segregation were observed between the ammonic and subicular plates. Moreover, an ammonic-to-subicular maturation gradient was observed in germinal/postmitotic areas. Taken together, these findings demonstrate for the first time the presence of an SVZ in the hippocampus of human fetuses and laminar differences in transcription factor expression in the pyramidal layer of the human ammonic and subicular plate, and provide new information to further investigate the connectivity of the hippocampal formation.

Involvement of the subplate zone in preterm infants with periventricular white matter injury.

Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical subplate zone. We studied the cortical wall of noncystic and cystic PWMI cases and controls. Non-cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post-mortem human frontal lobes from very preterm [24­29 postconceptional weeks (pcw)] and preterm infants (30­34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1(MCT1), ionized calcium-binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the subplate in non-cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age-related and laminar differences were observed in non-cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the subplate but throughout the cortical plate. There were no differences in Olig2-positive pre-oligodendrocytes in the subplate inPWMI cases compared with controls. The involvement of gliosis in the deep subplate supports the concept of the complex cellular vulnerability of the subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI.

Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain.

OBJECTIVE: Activated microglia play a central role in the inflammatory and excitotoxic component of various acute and chronic neurological disorders. However, the mechanisms leading to their activation in the latter context are poorly understood, particularly the involvement of N-methyl-D-aspartate receptors (NMDARs), which are critical for excitotoxicity in neurons. We hypothesized that microglia express functional NMDARs and that their activation would trigger neuronal cell death in the brain by modulating inflammation. METHODS AND RESULTS: We demonstrate that microglia express NMDARs in the murine and human central nervous system and that these receptors are functional in vitro. We show that NMDAR stimulation triggers microglia activation in vitro and secretion of factors that induce cell death of cortical neurons. These damaged neurons are further shown to activate microglial NMDARs and trigger a release of neurotoxic factors from microglia in vitro, indicating that microglia can signal back to neurons and possibly induce, aggravate, and/or maintain neurologic disease. Neuronal cell death was significantly reduced through pharmacological inhibition or genetically induced loss of function of the microglial NMDARs. We generated Nr1 LoxP(+/+) LysM Cre(+/-) mice lacking the NMDAR subunit NR1 in cells of the myeloid lineage. In this model, we further demonstrate that a loss of function of the essential NMDAR subunit NR1 protects from excitotoxic neuronal cell death in vivo and from traumatic brain injury. INTERPRETATION: Our findings link inflammation and excitotoxicity in a potential vicious circle and indicate that an activation of the microglial NMDARs plays a pivotal role in neuronal cell death in the perinatal and adult brain.

Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex.

Early life adverse events can lead to structural and functional impairments in the prefrontal cortex (PFC). Here, we investigated whether maternal deprivation (MD) alters PFC-dependent executive functions, neurons and astrocytes number and synaptic plasticity in adult male Long-Evans rats. The deprivation protocol consisted of a daily separation of newborn Long-Evans pups from their mothers and littermates 3h/day postnatal day 1-14. Cognitive performances were assessed in adulthood using the temporal order memory task (TMT) and the attentional set-shifting task (ASST) that principally implicates the PFC and the Morris water maze task (WMT) that does not essentially rely on the PFC. The neurons and astrocytes of the prelimbic (PrL) area of the medial PFC (mPFC) were immunolabelled respectively with anti-NeuN and anti-GFAP antibodies and quantified by stereology. The field potentials evoked by electrical stimulation of ventral hippocampus (ventral HPC) were recorded in vivo in the PrL area. In adulthood, MD produced cognitive deficits in two PFC-dependent tasks, the TMT and ASST, but not in the WMT. In parallel, MD induced in the prelimbic area of the medial PFC an upregulation of long-term potentiation (LTP), without any change in the number of neurons and astrocytes. We provide evidence that MD leads in adults to an alteration of the cognitive abilities dependent on the PFC, and to an exaggerated synaptic plasticity in this region. We suggest that this latter phenomenon may contribute to the impairments in the cognitive tasks.

Perinatal cerebellar injury in human and animal models.

Cerebellar injury is increasingly recognized through advanced neonatal brain imaging as a complication of premature birth. Survivors of preterm birth demonstrate a constellation of long-term neurodevelopmental deficits, many of which are potentially referable to cerebellar injury, including impaired motor functions such as fine motor incoordination, impaired motor sequencing and also cognitive, behavioral dysfunction among older patients. This paper reviews the morphogenesis and histogenesis of the human and rodent developing cerebellum, and its more frequent injuries in preterm. Most cerebellar lesions are cerebellar hemorrhage and infarction usually leading to cerebellar abnormalities and/or atrophy, but the exact pathogenesis of lesions of the cerebellum is unknown. The different mechanisms involved have been investigated with animal models and are primarily hypoxia, ischemia, infection, and inflammation Exposure to drugs and undernutrition can also induce cerebellar abnormalities. Different models are detailed to analyze these various disturbances of cerebellar development around birth.

DYRK1A: a master regulatory protein controlling brain growth.

Copy number variation in a small region of chromosome 21 containing DYRK1A produces morphological and cognitive alterations in human. In mouse models, haploinsufficiency results in microcephaly, and a human DYRK1A gain-of-function model (three alleles) exhibits increased brain volume. To investigate these developmental aspects, we used a murine BAC clone containing the entire gene to construct an overexpression model driven by endogenous regulatory sequences. We compared this new model to two other mouse models with three copies of Dyrk1a, YACtgDyrk1a and Ts65Dn, as well as the loss-of-function model with one copy (Dyrk1a(+/-)). Growth, viability, brain weight, and brain volume depended strongly upon gene copy number. Brain region-specific variations observed in gain-of-function models mirror their counterparts in the loss-of-function model. Some variations, such as increased volume of the superior colliculus and ventricles, were observed in both the BAC transgenic and Ts65Dn mice. Using unbiased stereology we found that, in the cortex, neuron density is inversely related to Dyrk1a copy number but, in thalamic nuclei, neuron density is directly related to copy number. In addition, six genes involved either in cell division (Ccnd1 and pAkt) or in neuronal machinery (Gap43, Map2, Syp, Snap25) were regulated by Dyrk1a throughout development, from birth to adult. These results imply that Dyrk1a expression alters different cellular processes during brain development. Dyrk1a, then, has two roles in the development process: shaping the brain and controlling the structure of neuronal components.

Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants.

Disabilities after brain injury in very preterm infants have mainly been attributed to noncystic periventricular white matter injury (PWMI). We analyzed spatiotemporal patterns of PWMI in the brains of 18 very preterm infants (25-29 postconceptional weeks [pcw]), 7 preterm infants (30-34 pcw), and 10 preterm controls without PWMI. In very preterm infants, we examined PWMI in detail in 2 axonal crossroad areas in the frontal lobe: C1 (lateral to the lateral angle of the anterior horn of the lateral ventricle, at the exit of the internal capsule radiations) and C2 (above the corpus callosum and dorsal angle of the anterior horn). These brains had greater microglia-macrophage densities and activation but lesser astroglial reaction (glial fibrillary acidic protein and monocarboxylate transporter 1 expression) than in preterm cases with PWMI. In preterm infants, scattered necrotic foci were rimmed by axonal spheroids and ionized calcium binding adaptor molecule 1-positive macrophages. Diffuse lesions near these foci consisted primarily of hypertrophic and reactive astrocytes associated with fewer microglia. No differences in Olig2-positive preoligodendrocytes between noncystic PWMI and control cases were found. These data show that the growing axonal crossroad areas are highly vulnerable to PWMI in very preterm infants and highlight differences in glial activation patterns between very preterm and preterm infants.

Neuroanatomical, sensorimotor and cognitive deficits in adult rats with white matter injury following prenatal ischemia.

Perinatal brain injury including white matter damage (WMD) is highly related to sensory, motor or cognitive impairments in humans born prematurely. Our aim was to examine the neuroanatomical, functional and behavioral changes in adult rats that experienced prenatal ischemia (PI), thereby inducing WMD. PI was induced by unilateral uterine artery ligation at E17 in pregnant rats. We assessed performances in gait, cognitive abilities and topographical organization of maps, and neuronal and glial density in primary motor and somatosensory cortices, the hippocampus and prefrontal cortex, as well as axonal degeneration and astrogliosis in white matter tracts. We found WMD in corpus callosum and brainstem, and associated with the hippocampus and somatosensory cortex, but not the motor cortex after PI. PI rats exhibited mild locomotor impairments associated with minor signs of spasticity. Motor map organization and neuronal density were normal in PI rats, contrasting with major somatosensory map disorganization, reduced neuronal density, and a marked reduction of inhibitory interneurons. PI rats exhibited spontaneous hyperactivity in open-field test and short-term memory deficits associated with abnormal neuronal density in related brain areas. Thus, this model reproduces in adult PI rats the main deficits observed in infants with a perinatal history of hypoxia-ischemia and WMD.

VIP blockade leads to microcephaly in mice via disruption of Mcph1-Chk1 signaling.

Autosomal recessive primary microcephaly (MCPH) is a genetic disorder that causes a reduction of cortical outgrowth without severe interference with cortical patterning. It is associated with mutations in a number of genes encoding protein involved in mitotic spindle formation and centrosomal activities or cell cycle control. We have shown previously that blocking vasoactive intestinal peptide (VIP) during gestation in mice by using a VIP antagonist (VA) results in microcephaly. Here, we have shown that the cortical abnormalities caused by prenatal VA administration mimic the phenotype described in MCPH patients and that VIP blockade during neurogenesis specifically disrupts Mcph1 signaling. VA administration reduced neuroepithelial progenitor proliferation by increasing cell cycle length and promoting cell cycle exit and premature neuronal differentiation. Quantitative RT-PCR and Western blot showed that VA downregulated Mcph1. Inhibition of Mcph1 expression led to downregulation of Chk1 and reduction of Chk1 kinase activity. The inhibition of Mcph1 and Chk1 affected the expression of a specific subset of cell cycle­controlling genes and turned off neural stem cell proliferation in neurospheres. Furthermore, in vitro silencing of either Mcph1 or Chk1 in neurospheres mimicked VA-induced inhibition of cell proliferation. These results demonstrate that VIP blockade induces microcephaly through Mcph1 signaling and suggest that VIP/Mcph1/Chk1 signaling is key for normal cortical development.

PCP4 (PEP19) overexpression induces premature neuronal differentiation associated with Ca(2+) /calmodulin-dependent kinase II-δ activation in mouse models of Down syndrome.

Pcp4/pep19 is a modulator of Ca(2+) -CaM, a key molecule for calcium signaling, expressed in postmitotic neuroectoderm cells during mouse embryogenesis. The PCP4 gene is located on human chromosome 21 and is present in three copies in Down syndrome (DS). To evaluate the consequences of three copies of this gene on the development of these cells in the nervous system, we constructed a transgenic (TgPCP4) mouse model, with one copy of human PCP4, and investigated the effects in this model and in the Ts1Cje, a mouse model of DS. During embryogenesis, we analyzed 1) the level of pcp4 transcript and protein in the two models; 2) the extent of colabeling for markers of neuronal differentiation (ßIII-tubulin, Map2c, calbindin, and calretinin) and pcp4 by immunofluorescence analysis and overall protein levels of these markers by Western blotting; and 3) the rate of activation of CaMKII, a Ca(2+) -CaM target, to evaluate the impact of pcp4 overexpression on the Ca(2+) -CaM signaling pathway. We showed that three copies of the pcp4 gene induced the overexpression of transcripts and proteins during embryogenesis. Pcp4 overexpression 1) induced precocious neuronal differentiation, as shown by the distribution and levels of early neuronal markers; and 2) was associated with an increase in CaMKIIδ activation, confirming involvement in neuronal differentiation in vivo via a Pcp4-Ca(2+) -CaM pathway. TgPCP4 and Ts1Cje mice developed similar modifications, demonstrating that these mechanisms may account for abnormal neuronal development in DS.

Slit2 activity in the migration of guidepost neurons shapes thalamic projections during development and evolution.

How brain connectivity has evolved to integrate the mammalian-specific neocortex remains largely unknown. Here, we address how dorsal thalamic axons, which constitute the main input to the neocortex, are directed internally to their evolutionary novel target in mammals, though they follow an external path to other targets in reptiles and birds. Using comparative studies and functional experiments in chick, we show that local species-specific differences in the migration of previously identified "corridor" guidepost neurons control the opening of a mammalian thalamocortical route. Using in vivo and ex vivo experiments in mice, we further demonstrate that the midline repellent Slit2 orients migration of corridor neurons and thereby switches thalamic axons from an external to a mammalian-specific internal path. Our study reveals that subtle differences in the migration of conserved intermediate target neurons trigger large-scale changes in thalamic connectivity, and opens perspectives on Slit functions and the evolution of brain wiring.

Cerebellar abnormalities following hypoxia alone compared to hypoxic-ischemic forebrain injury in the developing rat brain.

Two-day-old (P2) rat pups were subjected to either a global hypoxia or to electrocoagulation of the right carotid artery followed by 2.5 h hypoxia. Cellular and regional injury in the cerebellum (CB) was studied at 1, 2 and 19 days using immunohistology. Following hypoxia and hypoxia-ischemia, all neuronal populations of the CB were damaged in a subset of Purkinje cells. The decrease in the number of interneurons, as well as the thickness of molecular and granular layers was significant following hypoxia. Diffuse white matter damage, with loss of preoligodendrocytes was more severe following hypoxia than hypoxia-ischemia. Global hypoxia in the rat at P2 produces extensive damage to many cell types in different areas of the CB. The addition of unilateral forebrain ischemia does not increase the severity of these changes. Our data provide insight into the mechanisms of the changes observed in the CB of premature newborns.

Early microglial colonization of the human forebrain and possible involvement in periventricular white-matter injury of preterm infants.

Amoeboid microglial subpopulations visualized by antibodies against ionized calcium-binding adapter molecule 1, CD68, and CD45 enter the forebrain starting at 4.5 postovulatory or gestational weeks (gw). They penetrate the telencephalon and diencephalon via the meninges, choroid plexus, and ventricular zone. Early colonization by amoeboid microglia-macrophages is first restricted to the white matter, where these cells migrate and accumulate in patches at the junctions of white-matter pathways, such as the three junctions that the internal capsule makes with the thalamocortical projection, external capsule and cerebral peduncle, respectively. In the cerebral cortex anlage, migration is mainly radial and tangential towards the immature white matter, subplate layer, and cortical plate, whereas pial cells populate the prospective layer I. A second wave of microglial cells penetrates the brain via the vascular route at about 12-13 gw and remains confined to the white matter. Two main findings deserve emphasis. First, microglia accumulate at 10-12 gw at the cortical plate-subplate junction, where the first synapses are detected. Second, microglia accumulate in restricted laminar bands, most notably around 19-30 gw, at the axonal crossroads in the white matter (semiovale centre) rostrally, extending caudally in the immature white matter to the visual radiations. This accumulation of proliferating microglia is located at the site of white-matter injury in premature neonates. The spatiotemporal organization of microglia in the immature white and grey matter suggests that these cells may play active roles in developmental processes such as axonal guidance, synaptogenesis, and neurodevelopmental apoptosis as well as in injuries to the developing brain, in particular in the periventricular white-matter injury of preterm infants.

Inflammation processes in perinatal brain damage.

Once viewed as an isolated, immune-privileged organ, the central nervous system has undergone a conceptual change. Neuroinflammation has moved into the focus of research work regarding pathomechanisms underlying perinatal brain damage. In this review, we provide an overview of current concepts regarding perinatal brain damage and the role of inflammation in the disease pathomechanism.