In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 20 ( 2001-09-25), p. 11720-11724
Abstract:
Neuronal injury in ischemic stroke is partly mediated by cytotoxic
reactive oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood–brain barrier (BBB),
its oxidized form, dehydroascorbic acid (DHA), enters the brain by means of facilitative transport. We hypothesized that i.v. DHA would
improve outcome after stroke because of its ability to cross the BBB and augment brain antioxidant levels. Reversible or permanent focal
cerebral ischemia was created by intraluminal middle cerebral artery occlusion in mice treated with vehicle, AA, or DHA (40, 250, or 500
mg/kg), either before or after ischemia. Given before ischemia, DHA
caused dose-dependent increases in postreperfusion cerebral blood flow, with reductions in neurological deficit and mortality. In reperfused
cerebral ischemia, mean infarct volume was reduced from 53% and 59% in vehicle- and AA-treated animals, respectively, to 15% in 250
mg/kg DHA-treated animals ( P 〈 0.05). Similar
significant reductions occurred in nonreperfused cerebral ischemia. Delayed postischemic DHA administration after 15 min or 3 h also
mediated improved outcomes. DHA (250 mg/kg or 500 mg/kg) administered at 3 h postischemia reduced infarct volume by 6- to
9-fold, to only 5% with the highest DHA dose ( P 〈 0.05). In contrast, AA had no effect on infarct volumes, mortality, or
neurological deficits. No differences in the incidence of intracerebral hemorrhage occurred. Unlike exogenous AA, DHA confers in
vivo , dose-dependent neuroprotection in reperfused and
nonreperfused cerebral ischemia at clinically relevant times. As a naturally occurring interconvertible form of AA with BBB permeability,
DHA represents a promising pharmacological therapy for stroke based on its effects in this model of cerebral ischemia.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.171325998
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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