TGFβ1 Treatment Reduces Hippocampal Damage, Spontaneous Recurrent Seizures, and Learning Memory Deficits in Pilocarpine-Treated Rats

Studies have demonstrated the neuroprotective activity of transforming growth factor beta-1 (TGF beta 1), protecting neurons against different kinds of insults. However, the role of exogenous TGF beta 1 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 TGF beta 1 administration on SRS and cognitive function following lithium-pilocarpine-induced SE and associated hippocampal damage. We found that intranasal TGF beta 1 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 TGF beta 1-treated rats compared to rats without TGF beta 1 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 TGF beta 1-treated rats compared to those without TGF beta 1 treatment. Our results indicate that intranasal delivery of TGF beta 1 immediately after SE induction not only protected against SRS but also improved cognitive function. The anti-epileptogenic properties of TGF beta 1 may be related to its effect of neuroprotection or to its effect of apoptosis pathway changes.