Abstract
Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction and neurological deficits following traumatic brain injury (TBI). The aim of the present study was to investigate the effects of progesterone on the expression of the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α) in the brain, BBB permeability, cerebral edema and neurological outcome, as well as to explore the mechanism of its neuroprotective effect. In this study, male rats were randomly divided into three groups: a sham-operated group (SHAM), a TBI group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was established using a modified Feeney’s weight-dropping method. Brain samples were extracted 24 h following injury. The expression levels of COX-2 and NF-κB were examined using immunohistochemistry, whilst the expression levels of PGE2 and TNF-α were detected by enzyme-linked immunosorbent assay. BBB permeability was analyzed using Evans blue and cerebral edema was determined using the dry-wet method. The neurological outcome was evaluated using the modified neurological severity score test. The results revealed that progesterone treatment significantly reduced post-injury inflammatory response, brain edema and Evans blue dye extravasation, and improved neurological scores compared with those in the TBI group. In conclusion, the inhibition of inflammation may be an important mechanism by which progesterone protects the BBB and improves neurological outcome.
Highlights
Traumatic brain injury (TBI) is caused by both primary and secondary injury
Nuclear factor κB (NF‐κB) is an important transcription factor complex that modulates the expression of numerous genes involved in immune and inflammatory responses, including COX‐2 and tumor necrosis factor‐α (TNF‐α), which are considered to be significant in secondary injury [4]
Immunohistochemical analysis revealed that the expression levels of COX‐2 and nuclear factor κB (NF‐κB) in the cortex were low in the sham‐operated group (SHAM) group
Summary
Primary injury occurs from the forces at the time of injury and is known to be irreversible It is the complex secondary mechanisms initiated at the time of trauma that have an important role in the delayed progression of the brain damage, which may present novel opportunities for therapeutic strategies. During post‐traumatic inflammation, metabolic products of arachidonic acid, known as prostanoids, including prostaglandins, prostacyclin and thromboxanes, are released These aggravate the injury process and have a central role in the central nervous system (CNS) in brain injury [2]. Following TBI, the overproduction of inflammatory mediators within the injured brain, including PGE2, COX‐2, NF‐κB and TNF‐α, are believed to contribute to the cerebral damage, cell death and BBB dysfunction [5]. Inflammation is a significant contributor to secondary injury, and control of the inflammatory response benefits BBB and neurological outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
