Neuroprotection with erythropoietin administration following controlled cortical impact injury in rats.
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 within 6 h of injury.
Cherian
Leela
L
Department of Neurosurgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. lcherian@bcm.tmc.edu
Goodman
J Clay
JC
Robertson
Claudia
C
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017078:Laser-Doppler Flowmetry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011994:Recombinant Proteins
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D001120:Arginine