The ubiquitin editing enzyme A20 (TNFAIP3) is upregulated during permanent middle cerebral artery occlusion but does not influence disease outcome

Cerebral ischemia is characterized by the activation of glial cells, causing a rapid and massive local inflammatory reaction that leads to tissue damage and neuronal cell death.1 Over the past decade, it has become increasingly clear that the transcription factor nuclear factor κB (NF-κB) has a central role in the pathogenesis of cerebral ischemia. The NF-κB family consists of five members, RelA (p65), RelB, c-Rel, p50 and p52, all of which are activated in the ischemic hemisphere of mice shortly after permanent middle cerebral artery occlusion (pMCAO), a well-established rodent model of focal cerebral ischemia.2 Furthermore, p50-deficient mice show a reduction in ischemic damage after pMCAO and transient MCAO followed by reperfusion, suggesting a cell death promoting role for NF-κB in this model.3, 4 In addition, mice lacking RelA in the central nervous system (CNS) also show reduced infarct size after 48 h of pMCOA, whereas germline deletion of the p52 or c-Rel subunits did not affect infarct volume.2 In line with findings that NF-κB has a detrimental role during ischemia, mice lacking IKK2 in all neuroectodermal cells or specifically in neurons show a decreased infarct volume 48 h after pMCAO, whereas constitutive activation of IKK2 increased infarct size.5 However, NF-κB may also act beneficial in conditions of ischemic preconditioning, which was shown to protect against a subsequent prolonged ischemic insult through transcriptional activation of NF-κB.6