Francesca Pischiutta

Bio: Francesca Pischiutta is an academic researcher from Mario Negri Institute for Pharmacological Research. The author has contributed to research in topics: Traumatic brain injury & Mesenchymal stem cell. The author has an hindex of 15, co-authored 20 publications receiving 915 citations.

The ischemic environment drives microglia and macrophage function.

Abstract: Cells of myeloid origin, such as microglia and macrophages, act at the crossroads of several inflammatory mechanisms during pathophysiology. Besides pro-inflammatory activity (M1 polarization), myeloid cells acquire protective functions (M2) and participate in the neuroprotective innate mechanisms after brain injury. Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Environmental changes affect microglia/macrophage functions. Hypoxia can affect myeloid cell distribution, activity, and phenotype. With their intrinsic differences, microglia and macrophages respond differently to hypoxia, the former depending on ATP to activate and the latter switching to anaerobic metabolism and adapting to hypoxia. Myeloid cell functions include homeostasis control, damage-sensing activity, chemotaxis, and phagocytosis, all distinctive features of these cells. Specific markers and morphologies enable to recognize each functional state. To ensure homeostasis and activate when needed, microglia/macrophage physiology is finely tuned. Microglia are controlled by several neuron-derived components, including contact-dependent inhibitory signals and soluble molecules. Changes in this control can cause chronic activation or priming with specific functional consequences. Strategies, such as stem cell treatment, may enhance microglia protective polarization. This review presents data from the literature that has greatly advanced our understanding of myeloid cell action in brain injury. We discuss the selective responses of microglia and macrophages to hypoxia after stroke and review relevant markers with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site. We also cover the functional consequences of chronically active microglia and review pivotal works on microglia regulation that offer new therapeutic possibilities for acute brain injury.

Human umbilical cord blood mesenchymal stem cells protect mice brain after trauma.

Abstract: Objective:To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential: 1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant change

Shape descriptors of the “never resting” microglia in three different acute brain injury models in mice

Abstract: The study of microglia and macrophage (M/M) morphology represents a key tool to understand the functional activation state and the pattern of distribution of these cells in acute brain injury. The identification of reliable quantitative morphological parameters is urgently needed to understand these cell roles in brain injury and to explore strategies aimed at therapeutically manipulating the inflammatory response. We used three different clinically relevant murine models of focal injury, namely, controlled cortical impact brain injury (traumatic brain injury (TBI)) and transient and permanent occlusion of middle cerebral artery (tMCAo and pMCAo, respectively). Twenty-four hours after injury, M/M cells were labeled by CD11b, and ×40 photomicrographs were acquired by unbiased sampling of the lesion core using a motorized stage microscope. Images were processed with Fiji software to obtain shape descriptors. We validated several parameters, including area, perimeter, Feret’s diameter (caliper), circularity, aspect ratio, and solidity, providing quantitative information on M/M morphology over wide tissue portions. We showed that the shape descriptors that best represent M/M ramification/elongation are area and perimeter, while circularity and solidity provide information on the ameboid shape. We also provide evidence of the involvement of different populations in local inflammatory events, with macrophages replacing microglia into the lesion core when reperfusion does not occur. Analysis of CD45high+ cell morphology, whose shape does not change, did not yield any difference, thus confirming the reliability of the approach. We have defined specific morphological features that M/M acquire in response to different acute insults by applying a sensitive and readily applicable approach to cell morphological analysis in the brain tissue. Potential application of this method can be extended to all cell types able to change shape following activation, e.g., astrocytes, or to different disease states, including chronic pathologies.

Microglia in Physiology and Disease

Abstract: As the immune-competent cells of the brain, microglia play an increasingly important role in maintaining normal brain function. They invade the brain early in development, transform into a highly ramified phenotype, and constantly screen their environment. Microglia are activated by any type of pathologic event or change in brain homeostasis. This activation process is highly diverse and depends on the context and type of the stressor or pathology. Microglia can strongly influence the pathologic outcome or response to a stressor due to the release of a plethora of substances, including cytokines, chemokines, and growth factors. They are the professional phagocytes of the brain and help orchestrate the immunological response by interacting with infiltrating immune cells. We describe here the diversity of microglia phenotypes and their responses in health, aging, and disease. We also review the current literature about the impact of lifestyle on microglia responses and discuss treatment options that modulate microglial phenotypes.

Modulators of microglial activation and polarization after intracerebral haemorrhage.

Abstract: Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment Microglia are among the first non-neuronal cells on the scene during the innate immune response to ICH Microglia respond to acute brain injury by becoming activated and developing classic M1-like (proinflammatory) or alternative M2-like (anti-inflammatory) phenotypes This polarization implies as yet unrecognized actions of microglia in ICH pathology and recovery, perhaps involving microglial production of proinflammatory or anti-inflammatory cytokines and chemokines Furthermore, alternatively activated M2-like microglia might promote phagocytosis of red blood cells and tissue debris, a major contribution to haematoma clearance Interactions between microglia and other cells modulate microglial activation and function, and are also important in ICH pathology This Review summarizes key studies on modulators of microglial activation and polarization after ICH, including M1-like and M2-like microglial phenotype markers, transcription factors and key signalling pathways Microglial phagocytosis, haematoma resolution, and the potential crosstalk between microglia and T lymphocytes, neurons, astrocytes, and oligodendrocytes in the ICH brain are described Finally, the clinical and translational implications of microglial polarization in ICH are presented, including the evidence that therapeutic approaches aimed at modulating microglial function might mitigate ICH injury and improve brain repair