RT Journal Article
SR Electronic
T1 Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 789
OP 794
DO 10.1124/jpet.107.119628
VO 322
IS 2
A1 Leela Cherian
A1 J. Clay Goodman
A1 Claudia Robertson
YR 2007
UL http://jpet.aspetjournals.org/content/322/2/789.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics