Apocynin in the Treatment of Ischemic Stroke

ABSTRACT

Apocynin has been used as an efficient inhibitor of the NADPH oxidase complex in experimental studies. NADPH oxidase was originally identified immune cells as playing an important microbicidal role. In cerebral ischemia, inflammation is increasingly being recognized as contributing negatively to neurological outcome, with NADPH-oxidase as an important source of superoxide. Recently, several forms of this oxidase have been found in a variety of non-immune cells. Neuronal NADPH oxidase is thought to participate in long-term potentiation and intercellular signaling. However, excessive superoxide production is damaging and has been shown to play an important role in the progression of brain injury. NADPH oxidase is a multisubunit complex composed of membrane-associated gp91phox and p22^phox subunits and cytosolic subunits, p47^phox, p67^phox, and p40^phox and Rac. When NADPH oxidase is activated through phosphorylatoin of p47^phox, cytosolic subunits translocate to the cell membrane and fuse with the catalytic subunit, gp91phox. The activated enzyme complex transports electrons to oxygen, thus producing the superoxide anion (O2 ^°–), a precursor of reactive oxygen species. An NADPH oxidase assembly inhibitor, apocynin, has been shown alleviate oxidative stress and improves neurological outcome after cerebral ischemia. There is recent interest in the role of NADPH oxidase and apocynin as neuroprotective strategies against ischemia. This review will focus on therapeutic effects of NADPH oxidase assembly and its inhibitor apocynin in stroke and other brain injuries.

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