维生素C前体降低小鼠卒中所致损害
&nbps;&nbps;&nbps;&nbps;WESTPORT, CT (Reuters Health) - New York-based scientists have identified a chemical form of vitamin C, dehydroascorbic acid (DHA), that is actively transported across the blood-brain barrier and limits neurologic damage in a mouse model of stroke.
&nbps;&nbps;&nbps;&nbps;Dr. E. Sander Connolly, Jr., of Columbia University and collaborators from Memorial Sloan-Kettering Cancer Center and Progenics Pharmaceuticals, Inc., report their discovery in the Proceedings of the National Academy of Sciences for September 25.
, http://www.100md.com
&nbps;&nbps;&nbps;&nbps;Vitamin C is effective in protecting cultured cells from the harmful effects of oxygen free radicals triggered by stroke, and therefore has been investigated as a stroke therapy, Dr. Connolly noted in comments to Reuters Health. Unfortunately, the antioxidant is ineffective against stroke-induced brain damage because it cannot penetrate the blood-brain barrier.
&nbps;&nbps;&nbps;&nbps;The scientists gave mice injections of sucrose, ascorbic acid, or DHA (40 mg/kg, 250 mg/kg, or 500 mg/kg) either before or after induction of focal cerebral ischemia. When given before ischemia was induced, DHA led to a dose-dependent increase in postreperfusion cerebral blood flow, with reductions in neurologic deficits and mortality, the team reports.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;Moreover, DHA injected either 15 minutes or 3 hours after induction of stroke significantly decreased the volume of damaged brain tissue and improved neurologic function in mice.
&nbps;&nbps;&nbps;&nbps;Specifically, the team reports that DHA administered at the higher doses 3 hours after ischemia onset reduced infarct volume 6- to 9-fold. Ascorbic acid injections had no effect on infarct volume, neurologic deficits, or mortality. There were no between-group differences in the occurrence of intracerebral hemorrhage.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;"The mechanism of this protection is, at least in part, mediated through improvements in collateral circulation," Dr. Connolly said. "DHA protected both animals undergoing early mechanical reperfusion as well as those with permanent vascular obstruction."
&nbps;&nbps;&nbps;&nbps;"Our results suggest that an antioxidant precursor that readily penetrates the blood-brain barrier has great promise in the treatment of stroke in humans," said Dr. Connolly. If additional studies in animals and then humans are encouraging, vitamin-based antioxidant therapy may play a major role in the hyperacute pre-hospital therapy of evolving stroke, she added.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;In a commentary, Drs. James McCulloch and Deborah Dewar from the University of Glasgow say that "anti-ischemic drug development is at a crossroads. In excess of $1 billion has already been expended in evaluating neuroprotective drugs targeted at neurotransmitter receptors or ion channels in stroke patients, without success."
&nbps;&nbps;&nbps;&nbps;"Pharmacological modification of oxidative damage is one of the most promising avenues," they conclude., 百拇医药
&nbps;&nbps;&nbps;&nbps;Dr. E. Sander Connolly, Jr., of Columbia University and collaborators from Memorial Sloan-Kettering Cancer Center and Progenics Pharmaceuticals, Inc., report their discovery in the Proceedings of the National Academy of Sciences for September 25.
, http://www.100md.com
&nbps;&nbps;&nbps;&nbps;Vitamin C is effective in protecting cultured cells from the harmful effects of oxygen free radicals triggered by stroke, and therefore has been investigated as a stroke therapy, Dr. Connolly noted in comments to Reuters Health. Unfortunately, the antioxidant is ineffective against stroke-induced brain damage because it cannot penetrate the blood-brain barrier.
&nbps;&nbps;&nbps;&nbps;The scientists gave mice injections of sucrose, ascorbic acid, or DHA (40 mg/kg, 250 mg/kg, or 500 mg/kg) either before or after induction of focal cerebral ischemia. When given before ischemia was induced, DHA led to a dose-dependent increase in postreperfusion cerebral blood flow, with reductions in neurologic deficits and mortality, the team reports.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;Moreover, DHA injected either 15 minutes or 3 hours after induction of stroke significantly decreased the volume of damaged brain tissue and improved neurologic function in mice.
&nbps;&nbps;&nbps;&nbps;Specifically, the team reports that DHA administered at the higher doses 3 hours after ischemia onset reduced infarct volume 6- to 9-fold. Ascorbic acid injections had no effect on infarct volume, neurologic deficits, or mortality. There were no between-group differences in the occurrence of intracerebral hemorrhage.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;"The mechanism of this protection is, at least in part, mediated through improvements in collateral circulation," Dr. Connolly said. "DHA protected both animals undergoing early mechanical reperfusion as well as those with permanent vascular obstruction."
&nbps;&nbps;&nbps;&nbps;"Our results suggest that an antioxidant precursor that readily penetrates the blood-brain barrier has great promise in the treatment of stroke in humans," said Dr. Connolly. If additional studies in animals and then humans are encouraging, vitamin-based antioxidant therapy may play a major role in the hyperacute pre-hospital therapy of evolving stroke, she added.
, 百拇医药
&nbps;&nbps;&nbps;&nbps;In a commentary, Drs. James McCulloch and Deborah Dewar from the University of Glasgow say that "anti-ischemic drug development is at a crossroads. In excess of $1 billion has already been expended in evaluating neuroprotective drugs targeted at neurotransmitter receptors or ion channels in stroke patients, without success."
&nbps;&nbps;&nbps;&nbps;"Pharmacological modification of oxidative damage is one of the most promising avenues," they conclude., 百拇医药
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