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The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ.<jats:italic>Lnk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibited increased NSPC proliferation after stroke, but not in intact brain or following status epilepticus. Deletion of<jats:italic>Lnk<\/jats:italic>caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells<jats:italic>in vitro<\/jats:italic>. We found that<jats:italic>Lnk<\/jats:italic>expression after stroke increased in SVZ through the transcription factors STAT1\/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain.<\/jats:p>","DOI":"10.1523\/jneurosci.0474-12.2012","type":"journal-article","created":{"date-parts":[[2012,4,11]],"date-time":"2012-04-11T16:29:13Z","timestamp":1334161753000},"page":"5151-5164","source":"Crossref","is-referenced-by-count":14,"title":["Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after 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