Status epilepticus triggers long-lasting activation of complement C1q-C3 signaling in the hippocampus that correlates with seizure frequency in experimental epilepsy

Emerging Roles for Microglial Phagocytic Signaling in Epilepsy

“…Although microglia are the professional phagocytes of the CNS, relatively little is known regarding their phagocytic profiles in epilepsy or their contribution to the neuropathology and pathophysiology of this disorder. The studies described here are the first to show that seizures promote alterations in phagocytosis-associated signaling molecules that result in neuroimmune interactions, 13,17,[19][20][21][22] increases in "find-me" 17,22,41 and "eat-me" 9,13,[33][34][35][36] signals, decreases in the phagocytosis of newborn apoptotic cells, 16 phagocytosis of viable newborn cells, 16,38 and increases in microglial phagocytic activity and/ or proliferation that parallel neuronal/synaptic loss, seizures, and cognitive decline. 21,35,41,42,[44][45][46] Thus, it is possible that microglia may modulate synaptic circuitries in epilepsy by improperly phagocytosing synaptic structures and neurons.…”

“…34 Similarly, long-lasting increases in the levels of C1q-C3 that correlate with seizure severity occur in adult rodent models of SE and acquired TLE. 33,35,36 It is possible that a complement-dependent microglial elimination of synapses may contribute to the exacerbated synaptic loss, seizures, and memory impairments that occur after SE and in epilepsy. 35 The overall functional impact of aberrant C1q-C3 signaling to epileptic networks would depend on the proportion of excitatory or inhibitory cells/synapses being phagocytosed-an idea that requires further investigation.…”

The impact of postsynaptic density 95 blocking peptide (Tat‐NR2B9c) and an iNOS inhibitor (1400W) on proteomic profile of the hippocampus in C57BL/6J mouse model of kainate‐induced epileptogenesis

“…They were accordingly considered to reflect the impact of KA‐induced SE rather than intervention with either PSD95BP or 1400W. Those proteins included complement C1q subcomponent subunit B (C1qB), GFAP, and galectin‐1, all of which have previously been implicated in epileptogenesis (Bischoff, Deogracias, Poirier, & Barde, ; Schartz, Wyatt‐Johnson, Price, Colin, & Brewster, ).…”

“…There is very recent evidence suggesting that C1q activation in microglia is an important mediator of neuroinflammation and epileptogenesis (Schartz et al, ). C1q proteins expressed during epileptogenesis also serve as extracellular organizers, responsible for recruitment, and clustering of functional KA receptors on the postsynaptic membrane in hippocampal pyramidal neurons (Matsuda et al, ), suggesting a role in the perpetuation of SRS and the possibility that they might be viable targets for antiepileptogenic drug development.…”

Microglia and its role in neurodegenerative diseases

“…Status epilepticus (SE) is a serious neurological condition. It has been mentioned in animal studies that SE may cause hyperactivation in hippocampal neurons related to seizure frequency (Schartz et al, 2018). In a recent study, glial cell activation was noted to be important in the development of epilepsy, and high-mobility group box-1was found to have an effect on glial cell activation through Toll-like receptor 4 / NFκB signaling pathway in epileptic seizures (Shi et al, 2018).…”