Rapid astrocyte and microglial activation following pilocarpine‐induced seizures in rats

Abstract

SUMMARYAstrocyte and microglial activation occurs following seizures and plays a role in epileptogenesis. However, the precise temporal and spatial response to seizures has not been fully examined. The pilocarpine model of temporal lobe epilepsy was selected to examine glial changes following seizures because morphological changes in the hippocampus closely mimic the human condition. Astrocytic and microglial changes in the hippocampus were examined during the first 5 days after pilocarpine-induced seizures in rats by analyzing GFAP, Iba1 and S100B-immunolabeling in CA1, CA3, and the hilus. Also, 3-dimensional reconstructions of microglial cells from the hilus and granule cell layer were analyzed. Lastly, astrocyte hypertrophy was examined in the hilus using electron microscopy. At 1 day after seizures and continuing throughout the 5 days examined, hypertrophied Iba1-labeled microglial cells and glial fibrillary acidic protein (GFAP)-labeled astrocytes were observed. At 1 and 2 days after seizures, significantly greater Iba1 immunolabeling was observed in CA1, CA3, and the hilus. In addition, both the area of Iba1 labeled processes and the number of their endings were increased in the hilus beginning at 1 day after seizures. S100B-immunolabeling was significantly elevated in CA3 at 1 day, in CA3 and CA1 at 2 days, and in all three hippocampal regions at 3 days after seizures. Electron microscopy confirmed astrocytic hypertrophy and demonstrated astrocytic cell bodies in the location where glial endfeet normally appear on capillaries. The differential response patterns of astrocytes and microglial cells following pilocarpine-induced seizures may signify their detrimental role in neuroinflammation after seizures.

Seizure-Induced Sympathoexcitation Is Caused by Activation of Glutamatergic Receptors in RVLM That Also Causes Proarrhythmogenic Changes Mediated by PACAP and Microglia in Rats

“…In the KA-induced seizure group, MAP and HR were increased by 21 Ϯ 4 mmHg ( p ϭ 0.008) and 32 Ϯ 7 bpm ( p ϭ 0.0001), respectively, compared with the vehicle-treated group (Fig. 3 B, C): the findings support the notion that seizure is the cause of the dramatic increase in sympathetic nerve activity, tachycardia, and pressor effects (Sakamoto et al, 2008;Bealer et al, 2010). Bilateral microinjection of PBS (50 nl) had a transient and nonsignificant effect on MAP, HR, and SNA, that lasted for only a few minutes (Fig.…”

“…Seizure-induced cardiovascular autonomic dysfunction is a common cause of sudden unexpected death in epilepsy (SUDEP), which accounts for 5%-17% deaths in people with epilepsy (Sakamoto et al, 2008;Surges et al, 2009;Bardai et al, 2012;Massey et al, 2014). The rostral ventrolateral medulla (RVLM) contains sympathetic premotor neurons (C1), which are a subset of catecholaminergic neurons that express all of the enzymes necessary for the synthesis of adrenaline (Schreihofer and Guyenet, 1997;Phillips et al, 2001).…”

“…The rostral ventrolateral medulla (RVLM) contains sympathetic premotor neurons (C1), which are a subset of catecholaminergic neurons that express all of the enzymes necessary for the synthesis of adrenaline (Schreihofer and Guyenet, 1997;Phillips et al, 2001). Sympathetic vasomotor tone and blood pressure are regulated by C1 neurons, and another smaller population of neurons that is also located in the RVLM, through their direct projections to the intermediolateral (IML) cell column (Ross et al, 1984;Guyenet, 2006;Pilowsky et al, 2009). Seizure-induced increased activity of C1 catecholaminergic neurons (c-fos) is well documented (Kanter et al, 1995;Silveira et al, 2000).…”

Investigations of hippocampal astrocytes in lipopolysaccharide-preconditioned rats in the pilocarpine model of epilepsy

“…approximately on days 1-3, immediate activation of astrocytes and microglia [8] and similar astrogliosis were demonstrated after KA administration to the rat hippocampus [21,22]. Two to three weeks after KA application, the astrocytes displayed changed morphology, but there were no changes after 90 days.…”

ONO‐2506 inhibits spike–wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation

“…Indeed, both pre-clinical and clinical studies have demonstrated the presence of glial abnormalities in epileptic regions (Griffin et al, 1995;Lee et al, 2007;Somera-Molina et al, 2007;Shapiro et al, 2008). Epileptic brain is characterized by profound astrogliotic reaction with morphological and functional changes in astrocytes (Seifert et al, 2006).…”