Inhibition of LPA Activity Provides Long-Term Neuroprotection in Mice with Brain Ischemic Stroke.

Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA antagonist, TCLPA, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA activity can provide long-term neuroprotection to mice with brain ischemic stroke.