Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis

Abstract

Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

Ca2+, Astrocyte Activation and Calcineurin/NFAT Signaling in Age-Related Neurodegenerative Diseases

“…Cell-specific expression patterns of CN in both humans and animal models can exhibit striking changes characterized by intense upregulation in subsets of activated astrocytes (Hashimoto et al, 1998 ; Celsi et al, 2007 ; Abdul et al, 2009 ; Lim et al, 2013 ; Liu et al, 2015 ; Watanabe et al, 2015 ; Pleiss et al, 2016b ; Sompol et al, 2017 ). Recent work using custom antibodies generated toward calpain-dependent proteolysis sites in the CN catalytic subunit, observed extensive labeling for a 45–48 kDa ΔCN proteolytic fragment in astrocytes and, to a seemingly lesser extent, neurons (Pleiss et al, 2016b ).…”

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

“…Certainly, calcineurin/NFAT signaling involvement was also shown in pathogenic processes of other models of status epilepticus, including intracerebral injection of kainic acid [ 255 ], bicuculline [ 256 ], and pilocarpine [ 33 ]. Notably, calcineurin inhibitor ascomycin mediated anticonvulsant and neuroprotective effects, in different epilepsy models, including picrotoxin and latrunculin A models [ 257 – 259 ].…”

Astroglial role in the pathophysiology of statusepilepticus: an overview

“…Moreover, astrocytic swelling has been reported to increase calcium-dependent gliotransmitter release due to volume-sensitive organic anion channels activation in hippocampal CA1 neurons [ 143 , 144 ]. Although the pathophysiological mechanisms of ischemia and brain traumatic injury are different from those of SE, both astrocytic activation and edema have been reported to be present in SE [ 145 ].…”

“…Other markers related to inflammatory actions in astrocytes have been studied in SE. A recent study done in a mice lithium-pilocarpine-induced model of SE, documented a link between calcineurin overexpression, brain edema and reactive astrogliosis in SE [ 145 ]. In this work, calcineurin expression matched the time of brain edema occurrence and preceded astrocytic proliferation.…”