Expression and clinical significance of non-phagocytic cell oxidase 2 and 4 after human traumatic brain injury

Abstract

The goal of this study was to examine NOX2 and NOX4 expression in clinical samples of patients with traumatic brain injury (TBI), and to explore the correlation of NOX2 and NOX4 expression with the severity of injury, duration of injury, and prognosis. Brain samples of 20 TBI patients within 1 cm of the contusion site were collected and grouped based on duration of injury, Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS), and immunofluorescence staining were performed to examine the expression levels of NOX2 and NOX4 in the neurons and astrocytes. We found that the expression level of NOX2 in neurons and positive rate of NOX2 expression in astrocytes peaked at 12-24 and 6-12 h after injury, respectively. The expression level of NOX4 in neurons peaked at 24-48 h, and the positive rate of NOX4 expression gradually increased with prolonged injury. We also found that the higher the GCS score, the lower the expression levels of NOX2 and NOX4 in neurons was, while higher the GCS score, the lower the positive rate of NOX4 expression in astrocytes was and the higher the GOS grade, the lower the positive rate of expression in astrocytes was. In conclusion, NOX2 and NOX4 expressions significantly increase at an early stage after TBI, and abnormal expressions of NOX2 and NOX4 are correlated to patient prognosis to certain extent.

NADPH oxidase in brain injury and neurodegenerative disorders

“…Similar to the results obtained in animal studies described above, immunofluorescent staining of human post-mortem TBI brain samples showed that NOX2 and NOX4 expression was increased in the cortex at 6–24 and 24–48 h after TBI, respectively, and abnormal NOX2 and NOX4 expression showed correlation to patient prognosis [188]. NOX4 expression has also been reported to be increased in postmortem brain samples from athletes diagnosed with chronic traumatic encephalopathy, and the increase in NOX4 activity correlated with increased superoxide formation [187].…”

“…Similarly, NOX2 knockout mice have decreased contusion size, as well as decreased superoxide and peroxynitrite metabolism, and a decreased number of apoptotic cells in the cortex after TBI, confirming a possible role for NOX2 in TBI pathology [185] (Table 2). While NOX4 has been reported to be elevated after TBI (like NOX2) [71, 187, 188], there have been as yet no comparable studies examining TBI pathology or outcome in NOX4 knockout mice. Thus, studies to address this deficit are needed.…”

Central Nervous System Injury and Nicotinamide Adenine Dinucleotide Phosphate Oxidase: Oxidative Stress and Therapeutic Targets

“…NOX2 and NOX4 have been identified in clinical brain tissue samples from 6 to 24 h and 24-48 h after injury, respectively. 77 Positive immunostaining for both NOX2 and NOX4 was negatively correlated with Glasgow Coma Score (GCS) in this study. Unfortunately, to date, no study has examined NOX expression beyond 48 h in clinical samples.…”

“…NOX2 and NOX4 have been specifically co-labeled within neurons and astrocytes after brain injury in human patients. 77 In this study, NOX2 was found to be upregulated in astrocytes acutely (6-12 h) and in neurons at a somewhat delayed time course (12-24 h). Rats show a similar pattern, with acute elevations in neuronal NOX2 and NOX4.…”

NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury

“…Several NOX isoforms have been studied in the context of TBI pathology both in humans and in rodents [12]. Postmortem analysis demonstrated a correlation between elevated NOX2 and NOX4 expression and clinical TBI severity [13, 14], and circulating neutrophils of TBI patients show increased NOX2 expression [15]. In rodents, our laboratory showed acutely increased NOX2 expression in the cortex and CA1 hippocampus in the days following TBI [16].…”