Figure 1

Functional and molecular effects of HDAC inhibitor treatment in stroke and CNS trauma. Examples of common cell damage mechanisms shared by traumatic CNS impact and stroke include excitotoxicity, calcium overload, oxidative stress, acute inflammation and apoptosis. The discovery that relative over-deacetylation is a hallmark of neurodegenerative disorders led to the hypothesis that its correction will improve injury outcome. HDAC inhibitor administration was shown to improve neurobehavioral performance, decrease lesion volume, reduce BBB permeability and attenuate neurodegeneration. This step has been suggested to be mediated by multiple mechanisms leading to the restoration of acetylation homeostasis, most likely involving augmented acetylation of histones as well as nonhistone targets, as described in the text. Functional improvement was associated with a multitude of cellular and molecular changes affecting factors known to convey neuroprotective or antiapoptotic properties and with antiinflammatory effects including attenuated gliosis as well as reduced levels of inflammatory mediators. Ac-p53, acetylated p53; COX-2, cyclooxygenase-2; GSK-3, glycogen synthase kinase 3; iNOS, inducible nitric oxide synthase; MMP9, matrix metalloproteinase 9; TF, transcription factor; TNFα, tumor necrosis factor-α.