PMID- 30755225
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20200225
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 16
IP  - 1
DP  - 2019 Feb 12
TI  - Annexin A1-derived peptide Ac(2-26) in a pilocarpine-induced status epilepticus 
      model: anti-inflammatory and neuroprotective effects.
PG  - 32
LID - 10.1186/s12974-019-1414-7 [doi]
LID - 32
AB  - BACKGROUND: The inflammatory process has been described as a crucial mechanism in 
      the pathophysiology of temporal lobe epilepsy. The anti-inflammatory protein 
      annexin A1 (ANXA1) represents an interesting target in the regulation of 
      neuroinflammation through the inhibition of leukocyte transmigration and the 
      release of proinflammatory mediators. In this study, the role of the 
      ANXA1-derived peptide Ac(2-26) in an experimental model of status epilepticus 
      (SE) was evaluated. METHODS: Male Wistar rats were divided into Naive, Sham, SE 
      and SE+Ac(2-26) groups, and SE was induced by intrahippocampal injection of 
      pilocarpine. In Sham animals, saline was applied into the hippocampus, and Naive 
      rats were only handled. Three doses of Ac(2-26) (1 mg/kg) were administered 
      intraperitoneally (i.p.) after 2, 8 and 14 h of SE induction. Finally, 24 h after 
      the experiment-onset, rats were euthanized for analyses of neuronal lesion and 
      inflammation. RESULTS: Pilocarpine induced generalised SE in all animals, causing 
      neuronal damage, and systemic treatment with Ac(2-26) decreased neuronal 
      degeneration and albumin levels in the hippocampus. Also, both SE groups showed 
      an intense influx of microglia, which was corroborated by high levels of ionised 
      calcium binding adaptor molecule 1(Iba-1) and monocyte chemoattractant protein-1 
      (MCP-1) in the hippocampus. Ac(2-26) reduced the astrocyte marker (glial 
      fibrillary acidic protein; GFAP) levels, as well as interleukin-1beta (IL-1beta), 
      interleukin-6 (IL-6) and growth-regulated alpha protein (GRO/KC). These effects 
      of the peptide were associated with the modulation of the levels of formyl 
      peptide receptor 2, a G-protein-coupled receptor that binds to Ac(2-26), and the 
      phosphorylated extracellular signal-regulated kinase (ERK) in the hippocampal 
      neurons. CONCLUSIONS: The data suggest a neuroprotective effect of Ac(2-26) in 
      the epileptogenic processes through downregulation of inflammatory mediators and 
      neuronal loss.
FAU - Gimenes, Alexandre D
AU  - Gimenes AD
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), 
      Sao Paulo, SP, 04023-900, Brazil.
FAU - Andrade, Bruna F D
AU  - Andrade BFD
AD  - Department of Molecular Biology, Sao Jose do Rio Preto School of Medicine 
      (FAMERP), Sao Jose do Rio Preto, SP, 15090-000, Brazil.
FAU - Pinotti, Jose Victor P
AU  - Pinotti JVP
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), 
      Sao Paulo, SP, 04023-900, Brazil.
FAU - Oliani, Sonia M
AU  - Oliani SM
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), 
      Sao Paulo, SP, 04023-900, Brazil.
AD  - From the Post-Graduation in Biosciences, Instituto de Biociencias, Letras e 
      Ciencias Exatas, Sao Paulo State University (IBILCE/UNESP), Sao Jose do Rio 
      Preto, SP, 15054-000, Brazil.
FAU - Galvis-Alonso, Orfa Y
AU  - Galvis-Alonso OY
AD  - Department of Molecular Biology, Sao Jose do Rio Preto School of Medicine 
      (FAMERP), Sao Jose do Rio Preto, SP, 15090-000, Brazil.
FAU - Gil, Cristiane D
AU  - Gil CD
AUID- ORCID: 0000-0001-6979-4126
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), 
      Sao Paulo, SP, 04023-900, Brazil. cristiane.gil@unifesp.br.
AD  - From the Post-Graduation in Biosciences, Instituto de Biociencias, Letras e 
      Ciencias Exatas, Sao Paulo State University (IBILCE/UNESP), Sao Jose do Rio 
      Preto, SP, 15054-000, Brazil. cristiane.gil@unifesp.br.
LA  - eng
GR  - 2017/26872-5/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 2016/02012-4/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 308144/2014-7/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
PT  - Journal Article
DEP - 20190212
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Annexin A1)
RN  - 0 (Anticonvulsants)
RN  - 0 (Cytokines)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Lipoxin)
RN  - 0 (annexin A1 peptide (2-26))
RN  - 0 (lipoxin A(4) receptor, rat)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - Q3JTX2Q7TU (Diazepam)
SB  - IM
MH  - Animals
MH  - Annexin A1/metabolism/*therapeutic use
MH  - Anticonvulsants/therapeutic use
MH  - Blood-Brain Barrier/drug effects/physiopathology
MH  - Cytokines/*metabolism
MH  - Diazepam/therapeutic use
MH  - Disease Models, Animal
MH  - Gliosis/etiology
MH  - Hippocampus/drug effects/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Muscarinic Agonists/toxicity
MH  - Nerve Degeneration/*drug therapy/etiology/pathology
MH  - Nerve Tissue Proteins/metabolism
MH  - Neuroglia/pathology
MH  - Neurons/drug effects
MH  - Neuroprotective Agents/*therapeutic use
MH  - Peptides/*therapeutic use
MH  - Pilocarpine/toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Lipoxin/metabolism
MH  - Status Epilepticus/chemically induced/*complications/*drug therapy
PMC - PMC6371492
OTO - NOTNLM
OT  - Cytokines
OT  - ERK
OT  - Fpr2
OT  - Glia
OT  - Hippocampus
OT  - Neuroinflammation
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All procedures were approved by the 
      Ethics Committee in Animal Experimentation of the Federal University of Sao Paulo 
      - UNIFESP (CEUA n degrees  295,805,081) and agreed with the guidelines established by the 
      National Council for the Control of Animal Experimentation (CONCEA). CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2019/02/14 06:00
MHDA- 2019/05/29 06:00
PMCR- 2019/02/12
CRDT- 2019/02/14 06:00
PHST- 2018/11/06 00:00 [received]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/02/14 06:00 [entrez]
PHST- 2019/02/14 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2019/02/12 00:00 [pmc-release]
AID - 10.1186/s12974-019-1414-7 [pii]
AID - 1414 [pii]
AID - 10.1186/s12974-019-1414-7 [doi]
PST - epublish
SO  - J Neuroinflammation. 2019 Feb 12;16(1):32. doi: 10.1186/s12974-019-1414-7.