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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on April 30, 2007; DOI: 10.1124/jpet.107.119628


0022-3565/07/3222-789-794$20.00
JPET 322:789-794, 2007
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TOXICOLOGY

Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats

Leela Cherian, J. Clay Goodman, and Claudia Robertson

Department of Neurosurgery Baylor College of Medicine, Houston, Texas

This study was designed to determine the effect of erythropoietin (Epo) on cerebral blood flow (CBF), nitric oxide (NO) concentration, and neurological outcome after traumatic brain injury. In one experiment, the hemodynamic effects of Epo were determined after controlled cortical impact injury (CCII) by measuring mean arterial pressure, intracranial pressure, CBF using laser Doppler flowmetry, and brain tissue NO concentrations using an NO electrode. In total, 41 rats were given either Epo (5000 U/kg) or saline s.c. 3 days before injury. In animals pretreated with saline, L-arginine but not D-arginine administration resulted in a significant increase in tissue NO concentrations and an improvement in CBF at the impact site. Likewise, in animals pretreated with Epo, L-arginine but not D-arginine given postinjury increased brain tissue NO concentrations and increased CBF. In another experiment, 74 rats underwent CCII (3-mm deformation, velocity 5 m/s), and they were given saline or Epo 5000 U/kg s.c. at 5 min, 1 h, 3 h, 6 h, 9 h, or 12 h postinjury. The contusion volume and cell counts of viable neurons in the CA1 and CA3 regions of the hippocampus were assessed at 2 weeks postinjury. The contusion volume was significantly reduced at 5 min, 1 h, 3 h, and 6 h postinjury Epo administration. The neuron density in the CA1 and CA3 region of the hippocampus was increased at 1, 3, and 6 h after injury. These data demonstrate the neuroprotective effects of Epo in traumatic injury, and the effects are optimal when Epo is given with in 6 h of injury.


Received January 11, 2007; accepted April 27, 2007.

Address correspondence to: Dr. Leela Cherian, Department of Neurosurgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: lcherian{at}bcm.tmc.edu







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