Cindy Bokobza

French Institute of Health and Medical Research | Inserm · U1141

Human mesenchymal stem cells modulate the immune response and are good candidates for cell therapy in neuroinflammatory brain disorders affecting both adult and premature infants. Recent evidence indicates that through their secretome, mesenchymal stem cells direct microglia, brain-resident immune cells, toward pro-regenerative functions, but the m...

Preterm birth and its related complications have become more and more common as neonatal medicine advances. The concept of “developmental origins of health and disease” has raised awareness of adverse perinatal events in the development of diseases later in life. To explore this concept, we propose that encephalopathy of prematurity (EoP) as a pote...

Around 1 of every 10 babies is born preterm, and the incidence of preterm birth has been rising. The long-term consequences of preterm survivors are not fully understood. Preterm birth is proven to be associated with metabolic diseases and related disorders later in life. Preterm newborns are susceptible to perinatal inflammatory events such as cho...

Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotiona...

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A....

Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a “gut-brain axis” and the impact of an alteration of gut microbiota composition in brain diseases. Recent research has highlighted how gut microbiota could a...

Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, inc...

Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that correspo...

Preterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecules that block oligodendrocyte differentiation, lead...

Objectives: In the premature newborn, perinatal inflammation mediated by microglia contributes significantly to neurodevelopmental injuries including white matter injury (WMI). Brain inflammation alters development through neuroinflammatory processes mediated by activation of homeostatic microglia toward a pro-inflammatory and neurotoxic phenotype...

Microglial activation during critical phases of brain development can result in short- and long-term consequences for neurological and psychiatric health. Several studies in humans and rodents have shown that microglial activation, leading to a transition from the homeostatic state toward a proinflammatory phenotype, has adverse effects on the deve...

Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Because 1 in 10 babies is born preterm cerebellar injury is a significant clinical problem. The causes of cerebellar damage are yet to be fully explained. Herein, we tested the hypothesis...

A leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptor...

Acquired perinatal brain injuries are a set of conditions that remains a key challenge for neonatologists and that have significant social, emotional and financial implications for our communities. In our perspective article, will introduce perinatal brain injury focusing specifically on the events leading to brain damage in preterm born infants an...

Perinatal brain injuries, including encephalopathy related to fetal growth restriction, encephalopathy of prematurity, neonatal encephalopathy of the term neonate, and neonatal stroke, are a major cause of neurodevelopmental disorders. They trigger cellular and molecular cascades that lead in many cases to permanent motor, cognitive, and/or behavio...

Ischemic stroke is one leading cause of death worldwide, and inflammation has been extensively associated with its ontogeny and subsequent brain lesions. MicroRNAs (miRs) are non-coding RNA molecules that specifically repress gene expression post-transcriptionally. Several miRs have been correlated with innate immune response, and evidence accumula...

While it is currently estimated that stroke causes eight million annual deaths worldwide, the death rate only gives a first account of the overall burden of disease. Ischemic stroke is caused by the blockade or occlusion of the cerebral artery compromising blood supply and energy flow to the brain. The likelihood of restoration of blood flow depend...

Cell death is a biological process that results in old cells dying and being replaced by new ones or maybe a result of pathological disorders, localized injury, or trauma resulting in the death of cells. There are many cell death pathways so far reported in various kinds of literature, and many are continuously being discovered and reported having...

Post-stroke angiogenic and neurogenic processes have become one of the highly studied domains to identify multifaceted therapeutic strategies bridging neurodevelopment and neuropathology. microRNAs (miRNAs) regulate the generation of new neurons in the stroke-damaged adult brain to propagate post-ischemic self-repair. Similarly, a large number of i...

MicroRNAs being one of the most diversely conserved regulatory non-coding RNAs with an immense role in various physiological and pathological processes, have found its ways into the spotlight. The exponential flow of data related to their discovery, target prediction, function, and interaction with other non-coding RNAs, etc. can be seen over the y...

Biomarker represents an unavoidable tool, having immense clinical utility serving the purpose of ease and accuracy in diagnosing a disease. Its clinical value extends beyond diagnosis to therapeutic applications for better treatment outcomes. The gold standard of protein biomarkers has outlasted over decades, but a slow progression of microRNAs (mi...

Post-stroke miRNA modulation is anticipated to revolutionize ischemic stroke therapeutic landscape despite the challenges and the future efforts necessary for the successful translation of preclinical observations to clinical practice. This chapter summarizes the currently employed strategies for the restoration or inhibition of microRNA (miRNA) fu...

MicroRNAs (miRs) are short single-stranded non-coding RNAs that regulate protein synthesis by translational repression or degradation by targeting mRNAs at the post-transcriptional level. Highly conserved across species, they are known to regulate many genes in critical pathways during the lifetime. Any dysregulation at the cellular level, but also...

Cerebrovascular disorders constitute the world’s leading cause of morbidity and mortality. The role of miRNAs in initiating and advancing cerebrovascular diseases has recently become an important focus of attention. Through this chapter, we provide a brief overview of the ever-expanding role of miRNAs as a diagnostic and therapeutic tool for cerebr...

The past decade witnessed a paradigm shift of attention from a protein-centric approach to RNA centric approach in understanding the complexity of multi-factorial diseases like ischemic stroke. Thus, marking the beginning of a new class of non-protein-coding genes, exemplified by the intense research on microRNA, in human physiology and disease. Ho...

It is not surprising, given the complexity of the central nervous system, that a vast number of unique brain-enriched microRNAs (miRNAs) are expressed differentially after an ischemic stroke. MicroRNAs control multifaceted pathophysiological events such as excitotoxicity, calcium overload, and oxidative stress within minutes of an inflammatory resp...

There has been an enormous increase in information relating to microRNA (miRNA) and its strategic role in numerous diseases. This book reviews the emerging role of microRNAs in cerebral ischemia, providing comprehensive details of the links between this small RNA molecule and ischemic stroke, the more prevalent of the two main types of stroke. The...

Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm-born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microgl...

Genetic anomalies have a role in autism spectrum disorders (ASD). Each genetic factor is responsible for a small fraction of cases. Environment factors, like preterm delivery, have an important role in ASD. Preterm infants have a 10-fold higher risk of developing ASD. Preterm birth is often associated with maternal/fetal inflammation, leading to a...

Microglia of the developing brain have unique functional properties but how their activation states is regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microgli...

Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic...