Date of Completion
James Chrobak; John Salomone; Etan Markus; Ted Rosenkrantz
Field of Study
Master of Arts
Children born prematurely or at very low birth weight (VLBW) have an increased risk for hypoxic ischemic brain injury (HI). HI refers to a lack of adequate blood and oxygen flow in the brain. HI can also occur in the term infant due to birth complications such as prolonged labor, placental dysfunction, or cord prolapse. In both populations (though exact patterns of neuropathology vary) brain damage is likely to occur in the form of decreased hippocampal and cortical volume, and enlargement of the ventricles (Kesler et al., 2004, Nagy et al., 2009). Resulting neuropathology can in turn lead to cognitive and behavioral deficits as children age. For example, children who suffer from HI are more likely to be diagnosed with developmental disabilities such as ADHD, as well as language and memory impairments throughout childhood.
Fortunately, hypoxia ischemia can be modeled in neonatal rats via carotid artery ligation, followed by a period of induced hypoxia. This animal model can produce brain injuries that roughly equate to functional injuries seen in term infants with HI when performed on P7, and also leads to similar cognitive and behavioral impairments. Using this P7 HI model to assess behavioral outcomes, our lab has previously reported deficits in HI males on a Morris water maze task (a measure of simple spatial learning and memory). Based on those findings, the current study sought to assess HI males on a more difficult memory task: the eight arm radial water maze, in which performance requires a heightened reliance on spatial working memory. This paradigm was modified to make the task progressively harder throughout 8 testing weeks, by way of opening additional arms every 2 weeks. Thus, testing proceeded as follows: Condition 1 (Weeks 1 and 2) --3 arms open; Condition 2 (Weeks 3 and 4) --5 arms open; Condition 3 (Weeks 5 and 6) --8 arms open; and Condition 4 (Weeks 7 and 8) --8 arms open, with a 1 hour delay between sample and test trials.
Results revealed that HI animals performed close to Sham levels in the earlier weeks of testing (Condition 1-3). However, during Week 2 of Condition 4, when a retention interval of 1 hour was introduced, we saw an emergent deficit in HI animals with more errors made. Further analysis of Weeks within each Condition revealed that both HI and Sham animals were learning the task as testing progressed. This combination of findings indicates that though both groups could learn the memory task, HI animals showed a deficit on the hardest Condition (implementation of an hour delay). Interestingly, though HI animals were making more errors than Shams in the later weeks of testing, they also were taking significantly less time to make an arm choice-- suggesting HI animals may act more impulsively. Taken together, our findings indicate a spatial working memory impairment in HI animals, as well as a potential attentional deficit that might be associated with the characteristics of ADHD in clinical populations. These results build a framework for additional studies assessing memory and attentional impairments in HI animals and provide further insight into the consequence of HI within the clinical population.
Smith, Amanda L., "Effects of Neonatal Hypoxic Ischemic Brain Injury on Spatial Working Memory" (2012). Master's Theses. 366.
R. Holly Fitch