Abstract TMP86: Hippocampal Neuron Loss, Synaptic Plasticity Deficits, And Impaired Learning And Memory In A Mouse Model Of Neonatal Middle Cerebral Artery Stroke

Abstract

Background: Cognitive deficits are common long-term sequelae after neonatal stroke, occurring in to 70% of school aged children. Despite this, chronic cognitive deficits have not been evaluated in animal models of neonatal stroke. Objective: To determine whether neonatal mice have behavioral memory and hippocampal cellular and plasticity changes after transient middle cerebral artery occlusion (tMCAO). Methods: C57/BL6 mice underwent 60 minutes of right tMCAO using the intraluminal filament model, or sham surgery, followed by reperfusion on postnatal day 10 (p10). Mice underwent contextual fear conditioning (CFC) testing to evaluate spatial memory 14 days after tMCAO (p24, juvenile equivalent). A separate set of animals were sacrificed at the same timepoint for Crestly Violet staining and stereology of CA1 neurons, or for LTP recordings. Increase in field excitatory post-synaptic potential (fEPSP) slope 60 min after theta-burst stimulation (TBS) was analyzed as a measurement of synaptic plasticity (LTP). Results: Animals had a significant decrease in % time freezing in the CFC paradigm 14 days after p10 tMCAO compared to sham surgery animals, indicating behavioral spatial memory impairment (Figure 1A). Animals who underwent p10 tMCAO also had a deficit in LTP after TBS in ipsilateral compared to contralateral CA1 (figure 1B). Animals had a decrease density of CA1 hippocampal neurons in the ipsilateral hippocampus compared to contralateral hippocampus 14 days after p10 tMCAO (Figure 1C). Conclusion: Our results show that neonatal stroke causes CA1 hippocampal pyramidal cell death and synaptic plasticity deficits which contribute to chronic memory impairment.