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http://dx.doi.org/10.5115/acb.2010.43.3.201

Combined actions of $Na^+/K^+$-ATPase, $NCX_1$ and glutamate dependent NMDA receptors in ischemic rat brain penumbra  

Park, Sung-Jin (Department of Anatomy, College of Medicine, Dongguk University)
Jung, Yong-Wook (Department of Anatomy, College of Medicine, Dongguk University)
Publication Information
Anatomy and Cell Biology / v.43, no.3, 2010 , pp. 201-210 More about this Journal
Abstract
Instrumental role of $Na^+$ and $Ca^{2+}$ influx via $Na^+/K^+$ adenosine triphosphatase ($Na^+/K^+$-ATPase) and $Na^+/Ca^{2+}$ 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 ($78{\pm}6%$, n=4, *P<0.05) and NCX1 ($144{\pm}2%$, 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 ($153{\pm}9%$, n=4, *P<0.05) whereas the expression of NR2B was significantly decreased ($37{\pm}2%$, 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: $40{\pm}7%$; NR2B: $120{\pm}16%$, 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 $Ca^{2+}$ overload cooperated by the increased NCX1 and NR2B-containing NMDA receptor which may play an important role in the pathogenesis of the penumbra.
Keywords
penumbra; $Na^+/K^+$-ATPase; NCX1; NMDA receptor;
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