Cerullo, Pierpaolo
(2014)
ROLE OF SODIUM/CALCIUM EXCHANGER IN NEURONAL DISFUNCTIONS FOLLOWING HYPOXIC-ISCHEMIC INJURY IN NEONATAL MICE.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
ROLE OF SODIUM/CALCIUM EXCHANGER IN NEURONAL DISFUNCTIONS FOLLOWING HYPOXIC-ISCHEMIC INJURY IN NEONATAL MICE |
| Autori: |
| Autore | Email |
|---|
| Cerullo, Pierpaolo | pierpaolocerullo@gmail.com |
|
| Data: |
31 Marzo 2014 |
| Numero di pagine: |
87 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Neuroscienze e Scienze Riproduttive ed Odontostomatologiche |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Neuroscienze |
| Ciclo di dottorato: |
26 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Annunziato, Lucio | lannunzi@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Pignataro, Giuseppe | [non definito] |
|
| Data: |
31 Marzo 2014 |
| Numero di pagine: |
87 |
| Parole chiave: |
neonatal hypoxia ischemia, NCX, behavioral studies |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/14 - Farmacologia |
[error in script]
[error in script]
| Depositato il: |
09 Apr 2014 08:29 |
| Ultima modifica: |
08 Mag 2017 01:00 |
| URI: |
http://www.fedoa.unina.it/id/eprint/9954 |
Abstract
Background: Hypoxic-ischemic encephalopathy (HIE) accounts for the majority of developmental, motor and cognitive deficits in children, leading to life-long neurological impairments. Since (1) transient brain ischemia followed by reoxygenation alters ionic homeostasis in adult brain and the plasma membrane sodium/calcium exchanger (NCX) plays a fundamental role in the maintenance of ionic homeostasis during brain ischemia, we aim to demonstrate the involvement of NCX in the pathophysiology of HIE.
Methods: Experimental HIE was induced in postnatal day 7 (P7) mice by unilateral elettrocoagulation of the right common carotid artery and subsequent 60 minutes exposure of animals to 8% O2. Expression profiles of NCX from embryos stage to adulthood was done using HI and naïve hippocampus mice. To assess the effect of NCX pharmacological activation, brain infarct volume was evaluated in propidium iodide stained hippocampus sections, obtained at several time points after the administration of the newly synthesized NCX activator, Neurounina. Moreover, the effect of NCX activation on learning and memory was evaluated in P60 mice.
Results: An age-dependent NCX-1 and NCX-3 increased expression was evidenced in immature hippocampus in wild-type untreated animals. By contrast NCX-1 and NCX-3 expression was significantly reduced starting from 7 days until 60 days after the hypoxic-ischemic insult. NCX-2 expression did not show any change in the naïve and HI mice at all considered time intervals. Notably, NCX pharmacological activation by the newly synthesized compound neurounina not only reduced infarct volume but improved also the spatial and object memory 8 weeks after HI induction in P7 mice. These findings suggest that an altered ionic homeostasis mediated by the reduced expression of NCX contributes to long-term cognitive deficits in neonatal mice exposed to HIE.
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