Objective  To investigate the effect of nuclear factor-κB (NF-κB) on the regulation of cyclooxygenase-2 (COX-2) and Caspase-3 in hippocampal neurons after traumatic brain injury (TBI) in rats

and explore the neuroprotective effect and the possible mechanism of progesterone (PROG) in hippocampal neurons after TBI. Methods  Forty-five male Spraque-Dawley rats were randomly divided into 3 groups: sham-ope

rated group (

n

=15)

TBI group (

n

=15) and PROG-treated group (

n

=15

intraperitoneal injection of PROG 16 mg/kg in 1 and 6 h after injury). The rat model of TBI was duplicated with the improved Feeney’s method. The rats were sacrificed in 24 h after injury and their brain was resected. Nissl staining

immunohistochemical staining and Western blot assay for NF-κB

COX-2 and Caspase-3 was used to observe the changes of positive cell numbers and protein levels in the hippocampal neurons. Results  The numbers of immunoreactive neurons to NF-κB (24.0±2.5)

COX-2 (35.9±2.7) and Caspase-3 (25.1±2.7) were significantly increased in the hippocampus at 24 h after TBI when compared with the positive neuron numbers of NF-κB (1.9±0.9)

COX-2 (1.5±0.7) and Caspase-3 (1.8±0.8) in sham group. After the treatment of PROG

the positive cell number of NF-κB (14.2±1.8)

COX-2 (16.6±2.7)

Caspase-3 (11.2±2.4) was reduced obviously as compared with the TBI group (

P

<

0.05). Conclusion  NF-κB signaling pathway may play an important role in the regulation of COX-2 and Caspase-3 in the hippocampus neurons after TBI in rats. PROG may influence the expression of NF-κB and protect the hippocampal neurons.