Ionic transporter activity in astrocytes, microglia, and oligodendrocytes during brain ischemia

Abstract

Glial cells constitute a large percentage of cells in the nervous system. During recent years, a large number of studies have critically attributed to glia a new role which no longer reflects the long-held view that glia constitute solely a silent and passive supportive scaffolding for brain cells. Indeed, it has been hypothesized that glia, partnering neurons, have a much more actively participating role in brain function. Alteration of intraglial ionic homeostasis in response to ischemic injury has a crucial role in inducing and maintaining glial responses in the ischemic brain. Therefore, glial transporters as potential candidates in stroke intervention are becoming promising targets to enhance an effective and additional therapy for brain ischemia. In this review, we will describe in detail the role played by ionic transporters in influencing astrocyte, microglia, and oligodendrocyte activity and the implications that these transporters have in the progression of ischemic lesion.

Figure 1

Schematic anatomic diagram describing distribution of the different astrocyte phenotypes in the postischemic brain. MCAO, middle cerebral artery occlusion.

Figure 2

Schematic anatomic diagrams describing the distribution of the different microglia phenotypes in the postischemic brain. MCAO, middle cerebral artery occlusion.

Figure 3

Schematic anatomic diagrams describing the distribution of the different adult oligodendrocyte (OLG) progenitor cells (OPCs) and OLG phenotypes in the postischemic brain. MCAO, middle cerebral artery occlusion.

Figure 4

Major ionic transporters expressed in microglia, astrocytes, and oligodendrocytes (OLGs). NBC, Na⁺/HCO3⁻ cotransporter; NCX, Na⁺/Ca²⁺ exchanger; NHE, Na⁺/H⁺ exchanger; NKCC, Na⁺–K⁺–Cl⁻ cotransporter.

Figure 5

Putative topology of Na⁺/Ca²⁺ exchanger (NCX).

Figure 6

(A–I) Photomicrographs showing round phagocytic croglia displaying both Na⁺/Ca²⁺ exchanger 1 (NCX1) and Iba1 immunoreactivity in the inner periischemic region (A–C), in the ischemic region more distal (D–F) or more proximal (G–I) to the middle cerebral artery. The schematic anatomical diagram at the left side of each photograph set describes the ischemic region from where the images were taken. Scale bars 50 μm.

Figure 7

(A) Schematic diagram of primary microglial cell culture obtained from brain of rats bearing tMCAO; (B–C) Colocalization of Na⁺/Ca²⁺ exchanger 1 (NCX1) with IB4–fluorescein isothiocyanate (FITC) in microglial cells obtained from the contralateral hemisphere (B) or from the core region of the ipsilateral hemisphere (C). Scale bars: 20 μm. (D) I_NCX traces recorded from IB4(+) microglia and IB4 (−) cells isolated from the core. (E) I_NCX quantification is expressed as current densities recorded in IB4(+) and IB4(−) cells obtained from the core and in the IB4(+) cells from the corresponding contralateral cortex (n=20 per group). *P<0.05. Modified from Boscia et al 2009. License number 3110331370094.

Figure 8

Putative topology of Na⁺/H⁺ exchanger (NHE).

Figure 9

Putative topology of Na⁺–K⁺–Cl⁻ cotransporter (NKCC).

Figure 10

Putative topology of Na⁺/HCO3⁻ cotransporter (NBC).