NOX4 and brain ischemia: On the other hand, Kleinschnitz et al. demonstrated that mice deficient in Nox4 (Nox4(–/–)) of either sex, but not those deficient for Nox1 or Nox2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia [58].