Abstract
BackgroundStroke is an important cause of morbidity and mortality and few therapies exist thus far. Mild hypothermia (33°C) is a promising neuroprotective strategy to improve outcome after ischemic stroke. However, its complete mechanism of action has not yet been fully elaborated. This study is the first to investigate whether this neuroprotection occurs through modulation of the neuroinflammatory response after stroke in a time-dependent manner.MethodsThe Endothelin-1 (Et-1) model was used to elicit a transient focal cerebral ischemia in male Wistar rats. In this model, the core and penumbra of the insult are represented by the striatum and the cortex respectively. We assessed the effects of 2 hours of hypothermia, started 20 minutes after Et-1 injection on neurological outcome and infarct volume. Furthermore, pro- and anti-inflammatory cytokine expression was determined using ELISA. Microgliosis and astrogliosis were investigated using CD-68 and GFAP staining respectively. All parameters were determined 8, 24, 72 hours and 1 week after the administration of Et-1.ResultsEt-1 infusion caused neurological deficit and a reproducible infarct size which increased up to 3 days after the insult. Both parameters were significantly reduced by hypothermia. The strongest reduction in infarct volume with hypothermia, at 3 days, corresponded with increased microglial activation. Reducing the brain temperature affected the stroke induced increase in interleukin-1β and tumor necrosis factor α in the striatum, 8 hours after its induction, but not at later time points. Transforming growth factor β increased as a function of time after the Et-1-induced insult and was not influenced by cooling. Hypothermia reduced astrogliosis at 1 and 3 days after stroke onset.ConclusionsThe beneficial effects of hypothermia after stroke on infarct volume and functional outcome coincide with a time-dependent modulation of the cytokine expression and gliosis.
Highlights
Stroke is an important cause of morbidity and mortality and few therapies exist far
To address these essential questions, we investigated the effects of a 2 hours mild hypothermic treatment on microgliosis, astrogliosis and cytokine production as a function of time up to 1 week after an Et-1-induced insult and compared the results with neurological outcome and infarct size at the same time points
This study is the first to examine the neuroinflammatory response as a function of time after hypothermia in the Et-1 model for transient focal cerebral ischemia
Summary
Stroke is an important cause of morbidity and mortality and few therapies exist far. It is generally acknowledged that many agents, proven neuroprotective in experimental models, fail in clinical practice, possibly because they cannot respond to the of the insult are represented by the ipsilateral striatum and cortex, respectively In this and in other MCA occlusion (MCAO) models, mild hypothermia (33°C) has proven to reduce the infarct volume by half, 24 hours after the administration of Et-1, as the result of an almost complete recovery of the penumbra [7,8]. At an early stage, reactive microglia have shown neurotoxic properties, while sustained activation appeared beneficial to neuronal repair [16,21] To address these essential questions, we investigated the effects of a 2 hours mild hypothermic treatment on microgliosis, astrogliosis and cytokine production as a function of time up to 1 week after an Et-1-induced insult and compared the results with neurological outcome and infarct size at the same time points. This study is the first to show that hypothermia has a modulatory effect on the neuroinflammatory response after an Et-1-induced stroke
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
