title: TGFβ1 treatment reduces hippocampal damage, spontaneous recurrent seizures, and learning memory deficits in pilocarpine-treated rats.
abstract: Studies have demonstrated the neuroprotective activity of transforming growth factor beta-1 (TGFβ1), protecting neurons against different kinds of insults. However, the role of exogenous TGFβ1 in the neuronal damage following status epilepticus (SE) and the related spontaneous recurrent seizures (SRS) is unknown. The present study aimed to determine the effect of intranasal TGFβ1 administration on SRS and cognitive function following lithium-pilocarpine-induced SE and associated hippocampal damage. We found that intranasal TGFβ1 significantly attenuated the hippocampal insults marked by hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, and Fluoro-Jade B staining by 24, 48, and 72 h after SE was induced. The expression of the apoptosis-suppressing protein, Bcl-2, was elevated, whereas the expression of the apoptosis-promoting proteins, Bax and Caspase-3, was suppressed in TGFβ1-treated rats compared to rats without TGFβ1 treatment by 24, 48, and 72 h following induction of SE. The seizure number, severity, and duration of SRS over a 1-month period of monitoring starting 15 days after SE induction as well as the cognitive deficits detected 45 days after SE induction were significantly reduced in TGFβ1-treated rats compared to those without TGFβ1 treatment. Our results indicate that intranasal delivery of TGFβ1 immediately after SE induction not only protected against SRS but also improved cognitive function. The anti-epileptogenic properties of TGFβ1 may be related to its effect of neuroprotection or to its effect of apoptosis pathway changes.
authors.affiliation: Epilepsy and Headache Group, Department of Neurology, the First Hospital of Anhui Medical University, Jixi Road 218, Hefei 230022, China.
authors.forename: Liang-Yong
authors.initials: LY
authors.lastname: Li
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Li
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Zhang
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D008094:Lithium; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D053773:Transforming Growth Factor beta1; D010862:Pilocarpine; D008094:Lithium