Morris water maze function and histologic characterization of two age-at-injury experimental models of controlled cortical impact in the immature rat
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Controlled cortical impact (CCI) is commonly used in adult animals to study focal traumatic brain injury (TBI). Our study aims to further study injury mechanisms in children and variable models of pathology in the developing brain.
Develop a focal injury model of experimental TBI in the immature, postnatal days (PND) 7 and 17 rats that underwent a CCI at varying depths of deflection, 1.5–2.5 mm compared with sham and then tested using the Morris water maze (MWM) beginning on post-injury day (PID) 11. Histopathologic analysis was performed at PID 1 and 28.
In PND 7, the 1.75- and 2.0-mm deflections (diameter (d) = 3 mm; velocity = 4 m/s; and duration = 500 ms) resulted in significant MWM deficits while the 1.5-mm injury did not produce MWM deficits vs. sham controls. In PND 17, all injury levels resulted in significant MWM deficits vs. sham controls with a graded response; the 1.5-mm deflection (d = 6 mm; velocity = 4 m/s; and duration = 500 ms) produced significantly less deficits as compared WITH the 2.0- and 2.5-mm injuries. Histologically, a graded injury response was also seen in both ages at injury with cortical and more severe injuries, hippocampal damage. Cortical contusion volume increased in most injury severities from PID 1 to 28 in both ages at injury while hippocampal volumes subsequently decreased.
CCI in PND 7 and 17 rat results in significant MWM deficits and cortical histopathology providing two different and unique experimental models of TBI in immature rats that may be useful in further investigations into the mechanisms and treatments of pediatric TBI.
KeywordsAge Animal studies Models of injury Pediatric brain injury Traumatic brain injury
The authors wish to thank the National Institute of Health for its support for PDA (NIH RO1 NS42298) and PMK (NIH RO1 NS 30318 and NS 38087). The authors also wish to thank Ms. Christina Casanova for her help in the manuscript preparation.
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