Date of Completion

6-28-2013

Embargo Period

1-28-2014

Keywords

hypoxia ischemia, neuroprotectants, animal model

Major Advisor

Dr. R. Holly Fitch

Associate Advisor

Dr. Ted Rosenkrantz

Associate Advisor

Dr. John Salamone

Associate Advisor

Dr.James Chrobak

Associate Advisor

Dr. Heather Bortfeld

Field of Study

Psychology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Children born prematurely or at very low birth weight (VLBW) are at increased risk for sustained brain injury, including hypoxic ischemic (HI) injury that can arise from blood and/or oxygen deprivation. Additionally, HI injury can arise in term infants suffering from birth complications (e.g., cord prolapse, placental disruptions). The location and type of HI injury is dependent on the time at which injury is sustained. Premature infants diagnosed with HI injury more often show white matter fiber tract damage, where-as term infants with HI typically show gray matter damage. Furthermore, studies on the neuro-inflammatory profile following neonatal HI injury in rodent models have demonstrated an exaggerated expression of inflammatory factors in P12 (term model) as compared to P1 (preterm) rodents. Given this background the first study presented here was desgined to investigate the differences in behavioral deficits and neuropathology characterizing P3 (preterm model) and P7 (term model) HI injured rodents. Results indicated wide-spread behavioral deficits and neuropathology in P7 HI injured rodents, and more specific behavioral deficits with no apparent neuropathology in P3 HI rodents. Based on the more severe behavioral and neuropathological outcomes seen following P7 HI injury, subsequent studies went on to explore the use of the putative neuroprotectants erythropoietin (Epo) and caffeine in this model. Results show that Epo can be used to prevent neuroanatomical alterations following neonatal HI injury, as well as resulting behavioral deficits. Additionally, data presented here further show that caffeine may only be effective in ameliorating task-specific behavioral deficits. Finally, results suggest that both of these compounds need to be administered as soon as possible following the induction of HI injury in order to obtain an optimal outcome. Our cummlative results have implications for future research investigating the effects of preterm versus term HI injury, as well as for th development of neuroprotective strategies following HI injury. Thuss, our results could be applied to human neonatal HI injured populations in order to optimaize treatment strategies.

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