Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia.
OBJECTIVE
The Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. In the brain, there are 3 different genes coding for 3 different proteins: NCX1, NCX2, and NCX3. The aim of this study was to determine whether NCX1, NCX2, and NCX3 might play a differential role in the development of cerebral injury induced by permanent middle cerebral artery occlusion (pMCAO).


METHODS
By means of Western blotting, NCX1, NCX2, and NCX3 protein expression was evaluated in the ischemic core and in the remaining nonischemic area of the slice at different time intervals starting from ischemia induction. The role of each isoform was also assessed with antisense oligodeoxynucleotides (ODNs) targeted for each isoform. These ODNs were continuously intracerebroventricularly infused with an osmotic minipump (1 microL/h) for 48 hours, 24 hours before pMCAO.


RESULTS
The results showed that after pMCAO all 3 NCX proteins were downregulated in ischemic core; NCX3 decreased in periinfarctual area whereas NCX1 and NCX2 were unchanged. The ODNs for NCX1 and NCX3 gene products were capable of inducing an increase in the ischemic lesion and to worsen neurological scores.


CONCLUSIONS
The results of this study suggest that in the neuroprotective effect exerted by NCX during ischemic injury, the major role is prevalently exerted by NCX1 and NCX3 gene products.
Pignataro
Giuseppe
G
Division of Pharmacology, Department of Neuroscience, University of Naples, Federico II Via S. Pansini 5, 80131 Naples, Italy.
Gala
Rosaria
R
Cuomo
Ornella
O
Tortiglione
Anna
A
Giaccio
Lucia
L
Castaldo
Pasqualina
P
Sirabella
Rossana
R
Matrone
Carmela
C
Canitano
Adriana
A
Amoroso
Salvatore
S
Di Renzo
Gianfranco
G
Annunziato
Lucio
L
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015870:Gene Expression; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
D026901:Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; C110927:Slc8a2 protein, rat; C491102:Slc8a3 protein, rat; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1