martino_personalecopia

Neuroimmunology

INSPE UNIT
Gianvito Martino, Head of Unit

martino.gianvito@hsr.it

Physiological (spontaneous) and reactive (reparative) regenerative processes are fundamental part of life and greatly differ among the different animals and tissues. While spontaneous regeneration naturally occurs upon cell attrition, reparative regeneration occurs as a consequence of tissue damage. Both spontaneous and reparative regeneration play an important role in maintaining the normal equilibrium of the central nervous system (CNS) as well as in promoting its repair upon injury. The Unit’s research activity is mainly focused on the study of the molecular and cellular pathways sustaining both spontaneous and reparative CNS regenerative processes in both the healthy and pathological conditions such as inflammation and neurodegeneration. The ultimate main goal of the unit is to develop more efficacious therapeutic strategies to combat still incurable CNS pathological conditions.

Research activities (updated 2014)

The central nervous system (CNS) has the intrinsic capability to repair itself when injured. Over the years a series of molecular and cellular innate repair mechanisms have been discovered and their ability to prevent irreversible tissue damage and irreversible neurological deficits has been characterized. Among cellular mechanisms, those sustained by neural stem/precursor cells (NPCs) – the self-renewing and multipotent cells of the CNS capable of driving neurogenesis and gliogenesis during development and adult life – play a crucial role. On one hand, endogenous NPCs maintain CNS homeostasis via a series of different mechanisms of action among which the most important ones are the production of newly generated neuronal and glial cells and the release of neuroprotective substances (i.e. cannabinoids). On the other hand, transplanted NPCs are capable of migrating into damaged CNS areas to promote functional and structural tissue repair via different mechanisms of action spanning from cell replacement to the release of soluble neuroprotective molecules (i.e. bystander effect).
The Neuroimmunology Unit main goals are the following:

  • analyze which are the molecular pathways that support the development of the brain during embryonic life and to understand whether or not those pathways are recapitulated after an inflammatory and/or degenerative insult in order to promote the regeneration of the CNS;
  • understand the molecular mechanisms that alter synaptic function during inflammatory processes and/or degenerative CNS processes;
  • develop genetic tools to study the function of endogenous NPCs residing within the CNS during the development and in the adult life, both in physiological and pathological conditions;
  • analyze the role of endogenous NPCs in maintaining the homeostasis of the CNS and/or to induce tissue repair by developing genetic and molecular tools capable of marking or effectively eliminate these cells;
  • establish alternative therapeutic strategies based on the transplantation of adult or reprogrammed NPCs or aimed at fostering the reparative potential of endogenous NPCs in acute and chronic CNS inflammatory disorders leading to irreversible neurodegeneration (i.e. multiple sclerosis, stroke
and spinal cord injury).

Whole mount reconstruction of blood vessels within the subventricular zone of the adult central nervous system (CNS). Blood vessels (white, CD31) are covered by pericytes (green, PDGFRb) and astrocytes (red, aSMA). The proliferation marker Ki67 is in blue (scale bar = 20 μm).

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