BDNF represents one of the major mediators of neuroplasticity. We wanted to evaluate one of the most interesting hypotheses: NOX2 plays a role in the involvement of the neurotrophic factor BDNF dysregulation and cognitive deficient after sepsis.

Mice with deficits of NOX regulatory subunit/NOX2 organizer p47^phox (p47^phox-/-) and wild-type (WT) mice were used. Lipopolysaccharide (LPS) intraperitoneal injection was used to induce systemic inflammation. Spatial learning and memory were compared among treatment groups using the radial-arm maze task. Brain tissues were evaluated for the transcript levels of proinflammatory cytokines, while immunofluorescence staining and immunoblotting were used to determine the damaged neurons and the levels of BDNF.

Cognitive impairment following systemic inflammation was significantly attenuated in the p47^phox-/- mice compared with the WT mice. We found that the levels of BDNF in astroglia and neurons were significantly reduced within 10 days after the LPS injection in parallel with glia activation and increased cytokines in brains. We further revealed that p47^phox deletion could reduce glia activation, BDNF downregulation, and cognitive deficits, compared to those in WT-type mice following LPS injection.