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318 LONG-TERM BENEFICIAL EFFECTS OF ERYTHROPOIETIN GIVEN AFTER NEONATAL STROKE IN POSTNATAL DAY-7 RATS
  1. T. C. Wen,
  2. M. Rogido,
  3. B. Lee,
  4. R. Thompson,
  5. T. Genetta,
  6. A. Sola
  1. Emory University School of Medicine, Atlanta

Abstract

Background We and others have shown that erythropoietin (Epo) attenuates neonatal brain injury caused by hypoxia-ischemia and neonatal stroke; however, little is known about the long-term effects of Epo on injury to the developing brain.

Objective To investigate the long-term effects of Epo on brain injury caused by focal cerebral ischemia (FCI) in postnatal day-7 (P7) rat pups.

Methods FCI was induced by using a modified intraluminal catheter technique causing middle cerebral artery occlusion in P7 rats, as previously described. The experimental groups included sham-operated (n = 15), FCI plus vehicle (n = 17) and FCI plus recombinant human Epo (n = 18). In Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg at 15 minutes after FCI, which was repeated at 1 and 2 days after FCI. At 6 and 12 weeks after surgery, animals were sacrificed, and body weight and brain weight were determined, and then their brains were cut into 2 mm coronal slices. The infarct area and volume were measured using Windows Image J. Statistical comparisons were conducted by using the two-tailed Mann-Whitney U-test.

Results In the vehicle-treated FCI group, focal cerebral insult caused a marked reduction in brain weight (6 weeks: 1.23 ± 0.1 g; 12 weeks: 1.50 ± 0.1 g; p = .0017), but there was no significant difference in body weight (6 weeks: 104.4 ± 13.7 g; 12 weeks: 352.0 ± 77.5 g), compared to the sham-operated group. Mean brain weight in the Epo-treated FCI group was significantly increased at 6 weeks (1.39 ± 0.1 g; p = .0015) and at 12 weeks (1.75 ± 0.14 g; p = .001) after FCI compared to the vehicle-treated group. Moreover, Epo treatment after FCI produced significant reductions in the mean infarct area and volume in comparison to vehicle-treated group at 6 weeks (infarct area: 38.2 ± 33.6 mm< vs 94.3 ± 23.4 mm<, p = .002; infarct volume: 67.8 ± 53.1 mm> vs 188.5 ± 46.9 mm>, p = .002) and at 12 weeks (infarct area: 67.4 ± 45.0 mm< vs 127.2 ± 21.9 mm<; infarct volume: 134.9 ± 89.9 mm> vs 253.3 ± 44.2 mm>).

Conclusion Epo administration after focal cerebral insult produces a significant neuroprotective benefit over a prolonged period in the developing rat brain with neonatal stroke. These findings indicate that Epo may indeed be of clinical use as a potential neuroprotective agent in neonatal ischemic injury.

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