Motheaten (me/me) mice deficient in SHP‐1 are less susceptible to focal cerebral ischemia

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.

Modulation of Inflammatory Responses After Global Ischemia by Transplanted Umbilical Cord Matrix Stem Cells

“…More recent studies have suggested the possibility that the increases in GFAP + astrocytic hypertrophy might be an astroglia reaction to ischemia and can actually have neuroprotective functions 31–33. Astrocytes can play a number of protective roles after ischemia, including the uptake and transport of glutamate and glucose, repair of the blood brain barrier, and the production and release of neurotrophic factors 34, 35.…”

On a Possible Growth Mechanism for Polycyclic Aromatic Hydrocarbon Dications: C7H62++C2H2

“…Previous reports have shown that increases in GFAP correlates well with neuronal death following injury [29, 30]. More recent studies have suggested the possibility that the increases in GFAP + astrocytic hypertrophy might be an astroglial reaction to ischemia and can actually have neuroprotective functions [31, –33]. Astrocytes can play a number of protective roles after ischemia, including the uptake and transport of glutamate and glucose, repair of the blood brain barrier, and the production and release of neurotrophic factors [34, 35].…”

Protein tyrosine phosphatase inhibition reduces degeneration of dopaminergic substantia nigra neurons and projections in 6‐OHDA treated adult rats

“…The identities of tyrosine phosphatases whose inhibition leads to improved neuronal survival remain to be identified. Phosphatases such as SHP‐1 are candidates, as it negatively regulates nerve growth factor (NGF)‐dependent neuronal survival in vitro through dephosphorylating TrkA (Marsh et al ., 2003) and conversely, ischemia‐induced neuronal death is decreased in SHP‐1 deficient mice in vivo (Beamer et al ., 2006). Several other protein tyrosine phosphatases undergo increased expression in polyglutamine expansion‐induced neurodegeneration and their inhibition can prevent neuronal cell death in vitro (Wu et al ., 2002).…”