Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
-
J. Cereb. Blood Flow Metab. · Apr 2013
Multicenter Study Clinical TrialUltrasonographic markers of vascular risk in patients with asymptomatic carotid stenosis.
Six-hundred twenty-one subjects with unilateral asymptomatic severe internal carotid artery (ICA) stenosis were prospectively evaluated with a median follow-up of 27 months (min=6, max=68). Vascular risk profile, plaque characteristic, stenosis progression, and common carotid artery intima-media thickness (IMT) were investigated in all patients. Outcome measures were occurrence of ischemic stroke ipsilateral to ICA stenosis and vascular death, while myocardial infarction, contralateral strokes, and transient ischemic attack were considered as competing events. ⋯ The progression of stenosis was a strong risk factor (hazard ratio=4.32). Finally, the role of carotid IMT was confirmed as crucial additional measure, with an increased risk by 25% for each 0.1 mm IMT increase. Our data suggest that IMT, stenosis progression and severity should be considered as risk factors for cerebrovascular events in asymptomatic subjects with severe ICA stenosis.
-
J. Cereb. Blood Flow Metab. · Apr 2013
Phenelzine mitochondrial functional preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation-derived aldehyde 4-hydroxy-2-nonenal.
Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, we first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), we evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. ⋯ In PZ-treated rats, RCR suppression was prevented (P<0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% (P<0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.
-
J. Cereb. Blood Flow Metab. · Apr 2013
P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse.
Glia-based neuroprotection strategies are emerging as promising new avenues to treat brain damage. We previously reported that activation of the glial-specific purinergic receptor, P2Y(1)R, reduces both astrocyte swelling and brain infarcts in a photothrombotic mouse model of stroke. These restorative effects were dependent on astrocyte mitochondrial metabolism. ⋯ Mice deficient in the astrocyte-specific type 2 inositol 1,4,5 trisphosphate (IP(3)) receptor exhibited aggravated ischemic dendritic damage after photothrombosis. Treatment of these mice with 2MeSADP did not invoke an intracellular Ca(2+) response, did not repolarize astrocyte mitochondria, and did not reduce or partially reverse neuronal lesions induced by photothrombotic stroke. These results demonstrate that IP(3)-Ca(2+) signaling in astrocytes is not only critical for P2Y(1)R-enhanced protection, but suggest that IP(3)-Ca(2+) signaling is also a key component of endogenous neuroprotection.