P2X7 receptors in cerebral ischemia

Bai, Hui‐Yu; Li, Aiping

doi:10.1007/s12264-013-1338-7

Cited by 19 publications

(14 citation statements)

References 64 publications

(209 reference statements)

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“…All application protocols are described in the 'Methods' section staining with specific antibodies revealed astroglial expression of P2X7 receptors in the juvenile rat hippocampus (Kukley et al 2001). It is especially interesting that both mechanical and ischemic injury led to the appearance of previously absent P2X7 receptor-immunoreactivity in accumbal and cortical astrocytes of rats (Franke et al 2001(Franke et al , 2004Bai and Li 2013).…”

Section: Discussionmentioning

confidence: 99%

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Rubini

Pagel

Mehri

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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P2X7 receptors have been suggested to be located both on neurons and astrocytes of the central and peripheral nervous systems. In the present Ca(2+)-imaging and patch-clamp study, we reinvestigated these findings on mixed neuronal-astrocytic cell cultures prepared from embryonic or newborn rat hippocampi. We found in a Mg(2+)-free bath medium that the prototypic P2X7 receptor agonist dibenzoyl-adenosine triphosphate (Bz-ATP) increased the intracellular Ca(2+) concentration ([Ca(2+)]i) both in the neuronal cell bodies and in their axo-dendritic processes only to a very minor extent. However, Bz-ATP produced marked [Ca(2+)]i transients in the neuronal processes, when they grew above a glial carpet, which was uniformly sensitive to Bz-ATP. These glial signals might be misinterpreted as neuronal responses because of the poor focal discrimination by a fluorescent microscope. Most astrocytes had a polygonal shape without clearly circumscribable boundaries, but a subgroup of them had neuron-like appearance. The cellular processes of this astrocytic subgroup, just as their cell somata and their polygonal counterparts, appeared to possess a high density of functional P2X7 receptors. In contrast to astrocytes, in a low Ca(2+)/no Mg(2+)-containing bath medium, hippocampal neurons failed to respond to Bz-ATP with membrane currents. In addition, neither the amplitude nor the frequency of spontaneous excitatory postsynaptic currents, representing the quantal release of glutamate, was modified by Bz-ATP. We conclude that cultured hippocampal neurons, in contrast to astrocytes, possess P2X7 receptors, if at all, only at a low density.

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Section: Discussionmentioning

confidence: 99%

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Rubini

Pagel

Mehri

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Downregulation of P2X 7 receptor expression in rat oligodendrocyte precursor cells occurs after hypoxic ischemia (Wang et al, 2009b). There is a recent review that discusses the role of P2X 7 receptors in cerebral ischemia (Bai and Li, 2013). Endothelial cells at the BBB were shown to be extremely susceptible to cell death in ischemic conditions, whereas the other BBB cells, astrocytes, and pericytes, were more resistant .…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…Medial cerebral artery occlusion as a model of focal cerebral ischemia leads to a massive outflow of ATP from damaged CNS cells and upregulates P2X7R-IR in the penumbra of the damaged brain area [39,40]. There is an early microglial response associated with the activation of this cell type followed by a late response restricted to neurons and astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone

et al. 2018

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Organotypic hippocampal slice cultures were used to model the effects of neuroinflammatory conditions following an epileptic state on functional P2X7 receptors (Rs) of subgranular zone (SGZ) neural progenitor cells (NPCs). The compound, 4-aminopyridine (4-AP), is known to cause pathological firing of neurons, consequently facilitating the release of various transmitter substances including ATP. Lipopolysaccharide (LPS) and interleukin-1β (IL-1β) both potentiated the dibenzoyl-ATP (Bz-ATP)-induced current amplitudes in NPCs, although via different mechanisms. Whereas LPS acted via promoting ATP release, IL-1β acted via its own receptor to directly influence P2X7Rs. Thus, the effect of LPS was inhibited by the ecto-ATPase inhibitor, apyrase, but not by the IL-1β antagonist, interleukin-1RA (IL-1RA); by contrast, the effect of IL-1β was inhibited by IL-1RA, but not by apyrase. Eventually, incubation with 4-AP upregulated the number of nestin/glial fibrillary acidic protein/P2X7R immunoreactive cells and their appropriate staining intensity, suggesting increased synthesis of P2X7Rs at NPCs. In conclusion, inflammatory cytokines accumulating after epilepsy-like neuronal firing may facilitate the effect of endogenous ATP at P2X7Rs of NPCs, thereby probably promoting necrosis/apoptosis and subsequent cell death.

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P2X7 receptors in cerebral ischemia

Cited by 19 publications

References 64 publications

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons

Purinergic Signaling and Blood Vessels in Health and Disease

Inflammatory Cytokines Facilitate the Sensitivity of P2X7 Receptors Toward Extracellular ATP at Neural Progenitor Cells of the Rodent Hippocampal Subgranular Zone

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