title: Increased CCL2, CCL3, CCL5, and IL-1β cytokine concentration in piriform cortex, hippocampus, and neocortex after pilocarpine-induced seizures.
abstract: BACKGROUND
  Cytokines and chemokines play an important role in the neuroinflammatory response to an initial precipitating injury such as status epilepticus (SE). These signaling molecules participate in recruitment of immune cells, including brain macrophages (microglia), as well as neuroplastic changes, deterioration of damaged tissue, and epileptogenesis. This study describes the temporal and brain region pattern expression of numerous cytokines, including chemokines, after pilocarpine-induced seizures and discusses them in the larger context of their potential involvement in the changes that precede the development of epilepsy.
  
  
  RESULTS
  Adult rats received pilocarpine to induce SE and 90 min after seizure onset were treated with diazepam to mitigate seizures. Rats were subsequently deeply anesthetized and brain regions (hippocampus, piriform cortex, neocortex, and cerebellum) were freshly dissected at 2, 6, and 24 h or 5 days after seizures. Using methodology identical to our previous studies, simultaneous assay of multiple cytokines (CCL2, CCL3, CCL5, interleukin IL-1β, tumor necrosis factor (TNF-α)), and vascular endothelial growth factor (VEGF) was performed and compared to control rats. These proteins were selected based on existing evidence implicating them in the epileptogenic progression. A robust increase in CCL2 and CCL3 concentrations in the hippocampus, piriform cortex, and neocortex was observed at all time-points. The concentrations peaked with a ~200-fold increase 24 h after seizures and were two orders of magnitude greater than the significant increases observed for CCL5 and IL-1β in the same brain structures. TNF-α levels were altered in the piriform cortex and neocortex (24 h) and in the hippocampus (5 days) after SE.
  
  
  CONCLUSIONS
  Pilocarpine-induced status epilepticus causes a rapid increase of multiple cytokines in limbic and neocortical regions. Understanding the precise spatial and temporal pattern of cytokines and chemokine changes could provide more viable therapeutic targets to reduce, reverse, or prevent the development of epilepsy following a precipitating injury.
authors.affiliation: Texas A&M University Health Science Center, Department of Surgery, Temple, TX, 76504, USA. arisi@unifesp.br.|Baylor Scott and White Health Care, Department of Neurosurgery, Temple, TX, 76504, USA. arisi@unifesp.br.|Central Texas Veterans Health Care System, Temple, TX, 76504, USA. arisi@unifesp.br.|Present address: Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, Lab 3A, São Paulo, SP, 04039-032, Brazil. arisi@unifesp.br.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Arisi
authors.affiliation: Texas A&M University Health Science Center, Department of Surgery, Temple, TX, 76504, USA. mairalicia@yahoo.com.br.|Baylor Scott and White Health Care, Department of Neurosurgery, Temple, TX, 76504, USA. mairalicia@yahoo.com.br.|Central Texas Veterans Health Care System, Temple, TX, 76504, USA. mairalicia@yahoo.com.br.|Present address: Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, Lab 3A, São Paulo, SP, 04039-032, Brazil. mairalicia@yahoo.com.br.
authors.forename: Maira L
authors.initials: ML
authors.lastname: Foresti
authors.affiliation: Texas A&M University Health Science Center, Department of Surgery, Temple, TX, 76504, USA. kakatki@txch.org.|Baylor Scott and White Health Care, Department of Neurosurgery, Temple, TX, 76504, USA. kakatki@txch.org.|Central Texas Veterans Health Care System, Temple, TX, 76504, USA. kakatki@txch.org.
authors.forename: Khurshed
authors.initials: K
authors.lastname: Katki
authors.affiliation: Texas A&M University Health Science Center, Department of Surgery, Temple, TX, 76504, USA. lshapiro@medicine.tamhsc.edu.|Baylor Scott and White Health Care, Department of Neurosurgery, Temple, TX, 76504, USA. lshapiro@medicine.tamhsc.edu.|Central Texas Veterans Health Care System, Temple, TX, 76504, USA. lshapiro@medicine.tamhsc.edu.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D010862:Pilocarpine / Q000009:adverse effects; D066195:Piriform Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D010862:Pilocarpine