title: Granulocyte colony-stimulating factor treatment prevents cognitive impairment following status epilepticus in rats.
abstract: Status epilepticus (SE) rendered selective neuronal loss and cognitive impairments. Previous studies proved that granulocyte colony-stimulating factor (G-CSF) acted as a neuroprotectant in some nervous diseases. However, no investigations were focused on whether G-CSF could protect the hippocampus from SE. In this study, we administered recombinant human G-CSF into Sprague-Dawley rats with lithium-pilocarpine-induced SE subcutaneously for three times. The Morris water maze was employed to determine spatial learning ability from the 15th to 20th days after the treatment. The quantitative terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining and levels of apoptosis-related molecules including cleaved caspase-3, Bcl-xL and Bax on hippocampal CA1 region were examined by immunohistochemical staining at the 3rd and the 5th day after the treatment. Moreover, the phosphorylation of AKT was evaluated with Western blot at the 6th, 24th and 48th hours after the treatment to explore apoptosis and detect the protective effects of G-CSF. We found G-CSF treatment prevented SE-induced cognitive impairments with the decreased escape latency time on the 17th (29.86+/-9.09 vs. 38.33+/-6.94, p<0.05) and 18th days (23.83+/-6.17 vs. 33.52+/-8.48, p<0.05). The reduced TUNEL staining demonstrated reduced neuronal apoptosis occurrences. The anti-apoptotic effects were associated with decreased cleaved caspase-3 and Bax expression and increased phosphorylation of AKT and Bcl-xL expression. Taken together, our results suggested that systemic G-CSF treatment conducted neuroprotective function following SE through an anti-apoptotic pathway and prevented cognitive impairments, which may provide novel insights into pathogenesis and treatment following SE injury.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenyong
authors.initials: W
authors.lastname: Wang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Sun
authors.forename: Dongyun
authors.initials: D
authors.lastname: Feng
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Deng
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Huaning
authors.initials: H
authors.lastname: Wang
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008094:Lithium; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D010862:Pilocarpine; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D010862:Pilocarpine; D016179:Granulocyte Colony-Stimulating Factor; D008094:Lithium; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3