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After ischemic stroke, apoptosis of neurons is a primary factor in determining outcome. Wnt3a is a naturally occurring protein that has been shown to have protective effects in the brain for traumatic brain injury. Although wnt3a has been investigated in the phenomena of neurogenesis, anti-apoptosis, and anti-inflammation, it has never been investigated as a therapy for stroke. We hypothesized that the potential neuroprotective agent wnt3a would reduce infarction and improve behavior following ischemic stroke by attenuating neuronal apoptosis and promoting cell survival through the Frizzled-1/PIWI1a/FOXM1 pathway in middle cerebral artery occlusion (MCAO) rats. A total of 229 Sprague Dawley rats were assigned to male, female, and 9-month-old male MCAO or sham groups followed by reperfusion 2 h after MCAO. Animals assigned to MCAO were either given wnt3a or its control. To explore the downstream …