Anat Cell Biol.  2010 Sep;43(3):201-210. 10.5115/acb.2010.43.3.201.

Combined actions of Na+/K+-ATPase, NCX1 and glutamate dependent NMDA receptors in ischemic rat brain penumbra

• Park S
• Jung Y

• KMID: 2168875
• DOI: http://doi.org/10.5115/acb.2010.43.3.201

Abstract

Instrumental role of Na+ and Ca2+ influx via Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) and Na+/Ca2+ exchanger 1 (NCX1) is examined in the N-Methyl-D-aspartate (NMDA) receptor-mediated pathogenesis of penumbra after focal cerebral ischemia. An experimental model of 3, 6, and 24 h focal cerebral ischemia by permanent occlusion of middle cerebral artery was developed in rats. The changes in protein expression of Na+/K+-ATPase and NCX1 as well as functional subunits of NMDA receptor 2A and 2B (NR2A and NR2B) in the penumbra were assessed using by quantitative immunoblottings. The most prominent changes of Na+/K+-ATPase (78+/-6%, n=4, *P<0.05) and NCX1 (144+/-2%, n=4, *P<0.05) in the penumbra were developed 24 h after focal cerebral ischemia. The expression of NR2A in the penumbra was significantly increased (153+/-9%, n=4, *P<0.05) whereas the expression of NR2B was significantly decreased (37+/-2%, n=4, *P<0.05) as compared with sham-operated controls 3 h after focal cerebral ischemia. However, the expression of NR2A and NR2B in the penumbra was reversed 24 h after focal cerebral ischemia (NR2A: 40+/-7%; NR2B: 120+/-16%, n=4, *P<0.05). Moreover, the decreased expression of neuronal nuclei (NeuN) in the penumbra was most prominent than that of glial fibrillary acidic protein (GFAP) 24 h after focal cerebral ischemia. These findings imply that intracellular Na+ accumulation via decreased Na+/K+-ATPase exacerbate the Ca2+ overload cooperated by the increased NCX1 and NR2B-containing NMDA receptor which may play an important role in the pathogenesis of the penumbra.

Keyword

penumbra; Na+/K+-ATPase; NCX1; NMDA receptor

MeSH Terms

Adenosine Triphosphatases
Animals
Brain
Brain Ischemia
Glial Fibrillary Acidic Protein
Glutamic Acid
Immunoblotting
Middle Cerebral Artery
Models, Theoretical
N-Methylaspartate
Neurons
Rats
Receptors, N-Methyl-D-Aspartate
Adenosine Triphosphatases
Glial Fibrillary Acidic Protein
Glutamic Acid
N-Methylaspartate
Receptors, N-Methyl-D-Aspartate