Traumatic brain injury (TBI) is the major cause of high mortality and disability rates worldwide. Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma (PPARγ) that can reduce inflammation following TBI. Clinically

neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPARγ in TBI animals

only few could be converted into clinical

since TBI mechanisms in humans and animals are not completely consistent. The present study

provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI. First

we detected interleukin-6 (IL-6)

nitric oxide (NO) and Caspase-3 in TBI clinical specimens

confirming a presence of a high expression of inflammatory factors. Western blot (WB)

quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect PPARγ

IL-6

and p-NF-κB to identify the mechanisms of neuroinflammation. Then

in the rat TBI model

neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPARγ activator) or T0070907 (PPARγ inhibitor)

and PPARγ

IL-6 and p-NF-κB were detected again by qRT-PCR

WB and immunofluorescence (IF). The obtained results revealed that: 1) increased expression of IL-6

NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI

and decreased PPARγ in brain tissue; 2) pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI; 3) the protective effect of pioglitazone was achieved by activating PPARγ and reducing NF-κB and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-κB/IL-6 pathway.