Table 1 Pre-clinical data on effects of rhEPO and cEPO in models of central nervous (cerebral and spinal cord) I/R injury
From: Erythropoietin in the critically ill: do we ask the right questions?
Species | Model | Dose (IU·kg-1) | Protocol | Outcome | Histology | Apoptosis | Reference |
|---|---|---|---|---|---|---|---|
Rat | Stroke: embolic middle cerebral artery occlusion | 500, 1,150, or 5,000 | 6, 24, and 48 h post-embolus | 50% improvement of foot-fault test and modified Neurological Severity Score | Dose-dependent reduction of infarct volume (17, 28, 36%); 3% reduction in activated microglial cells | 31% drop in TUNEL cells | [18] |
Rat | Stroke: left internal carotid artery occlusion | 5,000 | Immediately, 12, and 24 h after ischemia | 20% improved 'corner test'; reduced oxidative stress and inflammation | Reduced infarct size (7 versus 25%); enhanced angiogenesis | 50% drop in TUNEL cells; increased Bcl expression | [19] |
Swine | Aortic balloon occlusion spinal cord ischemia/reperfusion injury | 5,000; cEPO-FC 50 μg·kg-1 | 30 minutes before, over 4 h after ischemia | Improved lower limb neurological function (response score: vehicle 0, rhEPO 4, cEPO-FC 4) and motor evoked potentials (vehicle 0, rhEPO 10, cEPO-FC 63% recovery); reduced oxidative stress (blood isoprostane levels) | Less NISSL-positive neurons (thoracic: vehicle 27, rhEPO 5 cEPO-FC 8%; lumbar: vehicle 26, rhEPO 8, cEPO-FC 7%) | No TUNEL and caspase-3-positive neurons | [17] |
Swine | Hypothermic circulatory arrest | 500 | 60 minutes before cardiac arrest | No difference in mortality or neurological outcome; lower glutamate and glycerol levels (cerebral microdialysis) | No difference in brain histology | Apoptotic index (TUNEL) 0.0 versus 0.99 | [27] |
Swine | Deep hypothermic circulatory arrest | 500 | 24 and 3 h before, 24 h after cardiac arrest | No difference in mortality or neurological outcome; lower S-100ß, lactate, and glycerol levels (cerebral microdialysis) | No difference in histology; reduced brain infarction (2/8 versus 8/8) | ND | [28] |
Swine | Aortic balloon occlusion spinal cord ischemia/reperfusion injury | 300 | 30 minutes before, over 4 h after ischemia | No differences in motor evoked potentials | Less NISSL-positive neurons in thoracic (25 versus 38%) spinal cord, lumbar spinal cord no difference | Thoracic spinal cord: less TUNEL cells (18 versus 65); lumbar spinal cord: no difference | [39] |