Abstract
We have demonstrated previously that the protein tyrosine phosphatase SHP‐1 seems to play a role in glial development and is upregulated in non‐dividing astrocytes after injury. The present study examines the effect of loss of SHP‐1 on the CNS response to permanent focal ischemia. SHP‐1 deficient (me/me) mice and wild‐type littermates received a permanent middle cerebral artery occlusion (MCAO). At 1, 3, and 7 days after MCAO, infarct volume, neuronal survival and cell death, gliosis, and inflammatory cytokine levels were quantified. SHP‐1 deficient me/me mice display smaller infarct volumes at 7 days post‐MCAO, increased neuronal survival within the ischemic penumbra, and decreased numbers of cleaved caspase 3+ cells within the ischemic core compared with wild‐type mice. In addition, me/me mice exhibit increases in GFAP+ reactive astrocytes, F4‐80+ microglia, and a concomitant increase in the level of interleukin 12 (IL‐12) over baseline compared with wild‐type. Taken together, these results demonstrate that loss of SHP‐1 results in greater healing of the infarct due to less apoptosis and more neuronal survival in the ischemic core and suggests that pharmacologic inactivation of SHP‐1 may have potential therapeutic value in limiting CNS degeneration after ischemic stroke. © 2006 Wiley‐Liss, Inc.