Biology Reference
In-Depth Information
Chapter 9
Erythropoietin and Cytoprotective Cytokines
in Experimental Traumatic Brain Injury
Samson Kumar Gaddam , Jovany Cruz , and Claudia Robertson
Abstract
The various biochemical cascades that follow primary brain injury result in secondary brain injury which
can adversely affect the clinical outcome. Over the last few years it has been well established that molecules
like erythropoietin (Epo) have a neuroprotective role in experimental traumatic brain injury (TBI). Epo is
shown to produce this effect by modulating multiple cellular processes, including apoptosis, inflammation,
and regulation of cerebral blood flow. Derivatives of Epo, including asialo Epo and carbamylated Epo,
have been developed to separate the neuroprotective properties from the erythropoiesis-stimulating activi-
ties of Epo which may have adverse effects in clinical situations. Peptides that mimic a portion of the Epo
molecule, including Helix B surface peptide and Epotris, have also been developed to isolate the neuro-
protective activities. The TBI model in rodents most commonly used to study the effect of Epo and these
derivatives in TBI is controlled cortical impact injury, which is a model of focal contusion following a high
velocity impact to the parietal cortex. Following TBI, rodents are given Epo or an Epo derivative vs. pla-
cebo and the outcome is evaluated in terms of physiological parameters (cerebral blood flow, intracranial
pressure, cerebral perfusion pressure), behavioral parameters (motor and memory), and histological param-
eters (contusion volumes, hippocampus cell counts).
Key words
Anesthesia, Behavior, Brain, Controlled cortical impact, Erythropoietin, Impactor,
Craniectomy, Traumatic brain injury
1
Introduction
TBI is the leading cause of disabling injuries in all age groups.
Apart from high mortality it can also result in significant morbid-
ity; both short term and long term. In USA alone, an estimated 5.3
million people live with TBI related disability (
1
). Even mild TBI
can result in cognitive problems that can affect activities of daily
living (
2
). The primary brain injury that occurs at the time of injury
is followed by several biochemical pathways in the brain that result
in secondary brain injury leading to raised intracranial pressure and
cerebral ischemia. Ischemia due to extracerebral causes (hypoten-
sion, anemia, and hypoxia) can also augment the secondary brain
injury. The current management of head injury patients involves
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