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Deferoxamine posttreatment reduces ischemic brain injury in neonatal rats.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Palmer, Charles Roberts, Rebecca L. Bero, C. J. |
| Copyright Year | 1994 |
| Abstract | BACKGROUND AND PURPOSE Iron catalyzes the formation of damaging reactive species during cerebral reperfusion. Brain iron concentration is highest at birth, so the brain of the asphyxiated newborn may be at increased risk of iron-dependent injury. We investigated whether the ferric iron chelator deferoxamine could reduce hypoxic-ischemic brain injury in neonatal rats. Because deferoxamine has concentration-dependent activities other than iron chelation, we measured brain deferoxamine levels and calculated deferoxamine pharmacokinetic parameters. METHODS We produced hypoxic-ischemic injury to the right cerebral hemisphere of 7-day-old rats by right common carotid artery ligation followed by 2.25 hours of hypoxia in 8% oxygen. At 5 minutes of recovery from hypoxia the rats received 100 mg/kg deferoxamine mesylate or saline subcutaneously. Rats (saline, n = 33; deferoxamine, n = 38) were killed at 42 hours of recovery to assess early acute edema by measurement of hemispheric water content. Other rats (saline, n = 31; deferoxamine, n = 32) were killed at 30 days of age for morphometric determination of right hemisphere atrophy. In still other rats, we measured deferoxamine levels in blood and brain after hypoxia-ischemia. RESULTS Deferoxamine significantly reduced right hemisphere injury as measured by early water content (P < .01) and later atrophy (P = .019). Deferoxamine brain levels peaked between 100 and 200 mumol/L at 40 to 60 minutes after injection and exceeded serum levels by +/- 70%. CONCLUSIONS Deferoxamine administered after induction of cerebral hypoxia-ischemia reduces injury in 7-day-old rats. Deferoxamine concentrates in the brain at levels between 100 and 200 mumol/L. At the concentrations achieved, deferoxamine might protect the brain through mechanisms unrelated to its ability to chelate iron. |
| Starting Page | 1424 |
| Ending Page | 1428 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://stroke.ahajournals.org/content/strokeaha/25/5/1039.full.pdf?download=true |
| Alternate Webpage(s) | http://stroke.ahajournals.org/content/strokeaha/25/5/1039.full.pdf |
| PubMed reference number | 8165675v1 |
| Volume Number | 25 |
| Issue Number | 5 |
| Journal | Stroke |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Atrophic Brain Hypoxia Brain Injuries Carotid Arteries Cerebral Hypoxia-Ischemia Cerebral Infarction Cerebral hemisphere structure (body structure) Chelating Activity Edema Ferric Hypoxia-Ischemia, Brain Hypoxic-Ischemic Encephalopathy Infant, Newborn Iron Chelating Agents Iron Chelation Ischemia Leukemia, Myelocytic, Acute Ligation Mesylates Oxygen deferoxamine mesylate mg/kg |
| Content Type | Text |
| Resource Type | Article |
