Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat brain after pentylenetetrazole-induced status epilepticus

Epilepsy Behav. 2013 Nov;29(2):275-80. doi: 10.1016/j.yebeh.2013.08.002. Epub 2013 Sep 6.


Population-based studies suggest that seizure incidence is highest during the first year of life, and early-life seizures frequently result in the development of epilepsy and behavioral alterations later in life. The early-life insults like status epilepticus often lead to epileptogenesis, a process in which initial brain injury triggers cascades of molecular, cellular, and network changes and eventually spontaneous seizures. Caffeic acid phenethyl ester is an active component of propolis obtained from honeybees and has neuroprotective properties. The aim of this study was to investigate whether caffeic acid phenethyl ester exerts neuroprotective effects on the developing rat brain after status epilepticus. Twenty-one dams reared Wistar male rats, and 21-day-old rats were divided into three groups: control group, pentylenetetrazole-induced status epilepticus group, and caffeic acid phenethyl ester-treated group. Status epilepticus was induced on the first day of experiment. Caffeic acid phenethyl ester injections (30 mg/kg intraperitoneally) started 40 min after the tonic phase of status epilepticus was reached, and the injections of caffeic acid phenethyl ester were repeated over 5 days. Rats were sacrificed, and brain tissues were collected on the 5th day of experiment after the last injection of caffeic acid phenethyl ester. Apoptotic cell death was evaluated. Histopathological examination showed that caffeic acid phenethyl ester significantly preserved the number of neurons in the CA1, CA3, and dentate gyrus regions of the hippocampus and the prefrontal cortex. It also diminished apoptosis in the hippocampus and the prefrontal cortex. In conclusion, this experimental study suggests that caffeic acid phenethyl ester administration may be neuroprotective in status epilepticus in the developing rat brain.

Keywords: CAPE; Caffeic acid phenethyl ester; Developing rat brain; Natural product: honeybee propolis; Neuroprotection; Propolis; SE; Seizure activity; Status epilepticus; TUNEL; Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling.

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Brain* / drug effects
  • Brain* / growth & development
  • Brain* / pathology
  • Caffeic Acids / therapeutic use*
  • Caspase 3 / metabolism
  • Convulsants / toxicity
  • Disease Models, Animal
  • In Situ Nick-End Labeling
  • Male
  • Neurons / drug effects*
  • Neuroprotective Agents / therapeutic use*
  • Pentylenetetrazole / toxicity
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / therapeutic use
  • Rats
  • Rats, Wistar
  • Status Epilepticus / chemically induced
  • Status Epilepticus / drug therapy
  • Status Epilepticus / pathology*


  • Caffeic Acids
  • Convulsants
  • Neuroprotective Agents
  • Caspase 3
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol
  • Pentylenetetrazole