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

Neurobiol Dis. 2018 Jan;109(Pt A):163-173. doi: 10.1016/j.nbd.2017.10.012. Epub 2017 Oct 23.


Status epilepticus (SE) triggers a myriad of neurological alterations that include unprovoked seizures, temporal lobe epilepsy (TLE), and cognitive deficits. Although SE-induced loss of hippocampal dendritic structures and synaptic remodeling are often associated with this pathophysiology, the underlying mechanisms remain elusive. Recent evidence points to the classical complement pathway as a potential mechanism. Signaling through the complement protein C1q to C3, which is cleaved into smaller biologically active fragments including C3b and iC3b, contributes to the elimination of synaptic structures in the normal developing brain and in models of neurodegenerative disorders. We recently found increased protein levels of C1q and iC3b fragments in human drug-resistant epilepsy. Thus, to identify a potential role for C1q-C3 in SE-induced epilepsy, we performed a temporal analysis of C1q protein levels and C3 cleavage in the hippocampus along with their association to seizures and hippocampal-dependent cognitive functions in a rat model of SE and acquired TLE. We found significant increases in the levels of C1q, C3, and iC3b in the hippocampus at 2-, 3- and 5-weeks after SE relative to controls (p<0.05). In the SE group, greater iC3b levels were significantly correlated with higher seizure frequency (p<0.05). Together, these data support that hyperactivation of the classical complement pathway after SE parallels the progression of epilepsy. Future studies will determine whether C1q-C3 signaling contributes to epileptogenic synaptic remodeling in the hippocampus.

Keywords: C1q; Classical complement pathway; Cognitive deficits; Epilepsy; Hippocampus; Microglia; Pilocarpine; Seizures; Status epilepticus.

MeSH terms

  • Animals
  • Complement C1q / metabolism*
  • Complement C3 / metabolism*
  • Epilepsy / chemically induced
  • Epilepsy / complications
  • Epilepsy / metabolism*
  • Hippocampus / metabolism*
  • Male
  • Pilocarpine / administration & dosage
  • Rats, Sprague-Dawley
  • Recognition, Psychology
  • Signal Transduction
  • Spatial Memory
  • Status Epilepticus / chemically induced
  • Status Epilepticus / complications
  • Status Epilepticus / metabolism*


  • Complement C3
  • Pilocarpine
  • Complement C1q