Abstract TP105: Short-Term Intraventricular Infusion of IGF-1 Following Stroke Decreases Behavioral Phenotypes of Depression in a Rat Ischemic Stroke Model

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Abstract

Background: Post stroke depression effects over one third of stroke survivors and adversely effects recovery. When left untreated, post stroke depression can lead to an increase in mortality rates, poorer prognosis, and a decrease in the quality of life during recovery. The peptide hormone insulin like growth factor IGF-1 has been shown in short term studies to reduced infarct volume and suppress inflammatory proteins, when measured 24h and 5d after stroke. We hypothesized that acute IGF-1 treatment will reduce the incidence of post stroke depression and will in turn improve long term recovery from stroke.

Methods: Middle aged (12 mo) female rats were used for these studies. All animals were pre-tested for sucrose preference and burrowing behavior and then subject to middle cerebral artery occlusion (MCAo). At 4h post-stroke, animals were randomly assigned to receive an intraventricular infusion of IGF-1 or artificial CSF control for 7 days. Animals were monitored for 5-9 weeks post stroke for survival and tested periodically for sucrose preference and burrowing (measures of anhedonia), and social interaction.

Results: Sucrose preference, measured at d10, 20, 30 post stroke was reduced in both groups following stroke, however there was a significant effect of IGF-1, such that sucrose preference was better preserved in IGF-1 treated animals as compared to controls. In the case of burrowing activity, which is a species typical behavior, control animals showed a decline in burrowing activity over day 10 to day 60 post stroke, while IGF-1 treated animals showed no significant decline. Social interaction at 60 days post stroke, as measured by time spent with a conspecific, was significantly reduced in control animals as compared to IGF-1 treated animals. Mortality among IGF-1-treated animals was 16.6% while mortality among vehicle treated animals was 38.8%. Kaplan Maier analysis of post stroke survival indicated a trend toward decreased mortality due to IGF-1 treatment (p<0.14).

Conclusion: The present data shows that behavioral phenotypes of depression are improved in IGF-1 treated animals. The data suggest that short term post-stroke IGF-1 treatment can exert beneficial effects on long term disability such as post stroke depression.

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