DOCOSAHEXAENOIC ACID UPREGULATES AKT PHOSPHORYLATION IN THE PENUMBRA AND IS NEUROPROTECTIVE IN EXPERIEMENTAL STROKE
Document Type
Presentation
Start Date
22-10-2010 8:30 AM
End Date
22-10-2010 8:45 AM
Description
The reperfusion phase of brain ischemia-reperfusion triggers the activation of pro-inflammatory, pro-apoptotic signaling cascades that ultimately result in cellular death and behavioral deficits. Systemically administered docosahexaenoic acid (DHA) attenuates infarct size and enhances recovery after middle cerebral artery occlusion (MCAo) (Belayev et al, Stroke, 2009). We hypothesize that DHA elicits neuroprotection by amplifying the activation of alternative prosurvival cascades thus tipping the overall cellular fate towards recovery and survival.
Sprague-Dawley rats (280-300g) underwent middle cerebral artery occlusion for 120mins followed by reperfusion. Arterial blood gases, plasma glucose, rectal and cranial temperatures were monitored throughout the surgery to ensure all animals remained within normal physiological conditions. Animals were randomly assigned to one of two treatment groups: ( 1) 5mg/kg DHA or (2) vehicle: 5ml/kg saline. Treatment was administered into the femoral vein 60 minutes after suture removal. All rats had a high-grade neurological deficit (at least 11 of a maximum 12) 60min after onset of MCA occlusion. Brain protein extracts from ipsilateral and contralateral penumbra! regions were collected at four and twenty-four hours and were analyzed by Western blots to compare the relative abundance of phosphorylated (activated) and total AKT1. The phosphorlyation of AKT is the first step in a variety of pro-survival cellular signaling cascades.
DHA given one hour after reperfusion significantly improves neurobehavioral outcome after MCAo. Systemic treatment with DHA significantly upregulates pAKT phosphorylation at Thr 308 (300%) and Ser473 (136%) in the penumbra at 4hrs relative to saline. The DHA induced upregulation of pAKT at Thr308 and Ser473 phosphorylation declines by 24hrs. This data suggests that DHA-mediated neuroprotection involves the initiation of pro-survival signaling pathways requiring the phosphorylation of AKT1 after stroke damage.
Recommended Citation
Eady, Tina; Belayev, L.; Khoutorova, L.; Atkins, K. D.; and Bazan, N. G., "DOCOSAHEXAENOIC ACID UPREGULATES AKT PHOSPHORYLATION IN THE PENUMBRA AND IS NEUROPROTECTIVE IN EXPERIEMENTAL STROKE" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 1.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation1/1
DOCOSAHEXAENOIC ACID UPREGULATES AKT PHOSPHORYLATION IN THE PENUMBRA AND IS NEUROPROTECTIVE IN EXPERIEMENTAL STROKE
The reperfusion phase of brain ischemia-reperfusion triggers the activation of pro-inflammatory, pro-apoptotic signaling cascades that ultimately result in cellular death and behavioral deficits. Systemically administered docosahexaenoic acid (DHA) attenuates infarct size and enhances recovery after middle cerebral artery occlusion (MCAo) (Belayev et al, Stroke, 2009). We hypothesize that DHA elicits neuroprotection by amplifying the activation of alternative prosurvival cascades thus tipping the overall cellular fate towards recovery and survival.
Sprague-Dawley rats (280-300g) underwent middle cerebral artery occlusion for 120mins followed by reperfusion. Arterial blood gases, plasma glucose, rectal and cranial temperatures were monitored throughout the surgery to ensure all animals remained within normal physiological conditions. Animals were randomly assigned to one of two treatment groups: ( 1) 5mg/kg DHA or (2) vehicle: 5ml/kg saline. Treatment was administered into the femoral vein 60 minutes after suture removal. All rats had a high-grade neurological deficit (at least 11 of a maximum 12) 60min after onset of MCA occlusion. Brain protein extracts from ipsilateral and contralateral penumbra! regions were collected at four and twenty-four hours and were analyzed by Western blots to compare the relative abundance of phosphorylated (activated) and total AKT1. The phosphorlyation of AKT is the first step in a variety of pro-survival cellular signaling cascades.
DHA given one hour after reperfusion significantly improves neurobehavioral outcome after MCAo. Systemic treatment with DHA significantly upregulates pAKT phosphorylation at Thr 308 (300%) and Ser473 (136%) in the penumbra at 4hrs relative to saline. The DHA induced upregulation of pAKT at Thr308 and Ser473 phosphorylation declines by 24hrs. This data suggests that DHA-mediated neuroprotection involves the initiation of pro-survival signaling pathways requiring the phosphorylation of AKT1 after stroke damage.