Hypoxic ischemic brain injury pathophysiology: a deeper understanding of hypoxia-resilient neurons and microvasculature modulation for post-cardiac arrest recovery (HIBImod)
| Componente | Categoria |
|---|---|
| Sonia Canterini | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Gianfranco Piccirillo | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Carmine Savoia | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Componente | Qualifica | Struttura | Categoria |
|---|---|---|---|
| Daniela Marazziti | Researcher | Institute of Cell Biology and Neurobiology, Italian National Research Council, Rome, Italy | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
| Piergiorgio La Rosa | RTD-A | Dipartimento Psicologia, Sapienza Università di Roma (hiring in process) | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Hypoxic-ischemic brain injury (HIBI) after cardiac arrest remains a challenging condition and an unresolved issue in clinical practice. The depletion of energy during ischemia and the induction of oxidative stress during reperfusion activates a number of molecular pathways that lead to cell death and finally to severe neurological damage. A reliable indicator of this damage is the insufficient recovery of normal EEG activity.
However, the brain is endowed with remarkable self-protection mechanisms, relying on the activation of a large array of molecular pathways, involving the so-called neurovascular unit (NVU). The reinstatement of the integrity of NVU, which includes the basal lamina, astrocytes, neurons, peri-capillary microglia, endothelial cells (ECs) and pericytes, is emerging as a crucial factor for successful recovery of ischemia-injured brain.
This proposal is grounded by the hypothesis that hypoxia resistant neurons in the post-ischemic brain can be gently electrically stimulated to trigger neuroprotection mechanisms in the ischemia-lesioned regions, steering durable changes towards normal activity patterns and functions. Using a rodent model of post-cardiac arrest recovery and ischemic brain damage, we will characterize neuroprotective mechanisms activated by ischemia-induced brain injury (HIBI), focusing the attention on both neuronal and microvasculature response. As a means to enhance intrinsic neuroprotective mechanisms, a non-invasive paradigm of broad neuronal activation by the cervical branch of the vagus nerve stimulation will be exploited. Biochemical changes activated by HIBI per se, and potentiated by VNS, are part of an enduring neuroprotective response, thus providing a significant window for pharmacological interventions.