Received for publication January 11, 2007.
Revised April 26, 2007.
Accepted for publication April 27, 2007.

Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats

Abstract

This study was designed to determine the effect of erythropoietin (Epo) on cerebral blood flow (CBF), nitric oxide (NO) concentration and on 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 (MAP), intracranial pressure (ICP), CBF using laser Doppler flowmetry (LDF), and brain tissue NO concentrations using an NO electrode. A total of 41 rats were given either Epo (5000units/kg) or saline SC three days prior to 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. Similarly, in animals pretreated with Epo, L-arginine but not D-arginine given post-injury increased brain tissue NO concentrations and increased CBF. In another experiment, 74 rats underwent CCII (3mm deformation, velocity 5m/sec) and were given saline or erythropoietin (Epo) 5000 units/kg SC at 5min, 1hr, 3hr, 6hr, 9hr, or 12hr post injury. The contusion volume and cell counts of viable neurons in the CA1 and CA3 regions of the hippocampus were assessed at 2 weeks post-injury. The contusion volume was significantly reduced at 5min, 1hr, 3hr and 6hr post injury EPO administration. The neuron density in the CA1and CA3 region of the hippocampus was increased at 1hr, 3hr, and 6hr after injury. These data demonstrate the neuroprotective effects of Epo in traumatic injury and the effects are optimal when Epo is given within 6 hrs of injury.

Key words: Cerebral blood flow, Neuroprotection, Nitric Oxide, cortical impact injury, erythropoietin, traumatic brain injury