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We used a total of 26 sexually-naive male and female Long Evans rats. The rats were housed in two microenvironments closed nest box (CN) or typical animal facility (AF) nesting. At PND7 neonatal HI was induced under Isoflurane using the Rice-Vannucci model of right common carotid artery ligation. After a 2 hr rest, the neonates were placed in a hypoxia chamber infused with 8% oxygen 92% nitrogen for 90 min.

The rats were exposed to cognitive testing to assess short and long-term visuo-spatial memory using the Morris water maze (MWM). MWM testing occurred PND 35-37 for three days of visible platform (VP) training with four different drop off locations (S,W,E,N) followed by five days of invisible platform (IP) training and 2 drop off locations (NW,NW,N,N).

On PND 50, the study was terminated: all study animals were given a novel stressor for 5 min in the elevated plus maze (EPM) then sacrificed 30 min later using live decapitation to harvest trunk blood and remove organs (including brain and spleen) for assessing weight and morphometry.

All analyses were done using SPSS 20.0 statistical software. We used a General Linear Mixed Model with repeated measures to analyze different time points across trials. Morphometry was assessed and reported with the help of a trained researcher.

Hypoxic-ischemic (HI) injury is one of the leading causes of severe neurological and behavioral deficits among full-term newborns. The purpose of this study was to determine whether an early, closed nest (CN) environment would reduce the neurological and behavioral deficits typically found in HI rat offspring compared to standard animal facility housing (AF). The brain area affected by HI involve the hippocampus and cortex, which are critical areas for spatial memory and navigation. 

Conclusions

References Fares, R.P., Belmenguenai, A., Sanchez, P.E.,

Kouchi, H.Y., Bodennec, J., Morales, A., Georges, A.et al., (2013). Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

Ivy, A., Brunson, K., Sandman, C., & Baram, T. (2008). Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relavent model for early-life stress. Neuroscience, 154, 1132-1142.

Lubics, A., Reglodi, D., Tamas, A., Kiss, P., Szalai, M., Szalontay, L., et al. (2005). Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury. Behavioural Brain Research, 157, 157-165.

Weaver, I. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., & ... Meaney, M. J. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7(8), 847-854. doi:10.1038/nn1276

Results

Logo

Water Maze

Patterns of Injury

Hippocampal damage

These findings point to plasticity post hypoxic ischemic injury in animals reared in the two micro-environments (CN housing compared to AF). Animals reared in CN housing performed better in both visible and invisible platform trials compared to those from AF housing. This implies that the HI injured pups with CN were more capable of using long term memory. CN pups were able to remember cues and find their way to the MWM platform faster than AF animals.

We hypothesize that these differences are due to maternal behavior. Previous studies have shown that environmental enrichment (Fares et al., 2013) and proper nesting (Ivy et al. 2008) influence maternal care. Maternal care does so by impacting epigenetic mechanisms (Weaver et al., 2004) that may regulate memory and hippocampal integrity. CN animals had much less global injury (infarct, enlarged ventricles) and less hippocampal atrophy compared to AF animals, and this paralleled their improved MWM performance.

These results indicate that a closed nesting environment can impact the course of neurodevelopment and recovery in neonatal HI, and that decreasing stress in the nesting environment may buffer the impact of HI and facilitate repair and recovery.

The effects of a closed nest pre-weaning environment on memory deficits in neonatal hypoxic-ischemic rats

Mitzi Sweeney, Hayley Santolucito, B.A., Aaron Thai, B.S., Laura Grace Rollins, M.A. and S. Tiffany Donaldson, Ph.D. Department of Psychology, University of Massachusetts Boston, Boston MA 02125

Abstract

Design and Methods

Figs. 1-2. Over 3 trials CN animals found their way to the VP faster than animals reared in AF. (*p = 0.001).

Visible Platform

Morphometry

 

 

A large infarct in the ipsilateral hemisphere,

spreading to the contralateral hemisphere

Enlarged right ventricle in the ipsilateral

hemisphere

Atrophy of cortex in ipsilateral hemisphere

Diffuse white matter damage in

periventricular area

 

A.

D.

C.

E.

B.

L R

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Figs. 3-4. Over 5 trials CN animals found their way to the IP platform faster than animals reared in AF. (*p=0.04).

Invisible Platform

Figure 4

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*

*

*

AF

AF

AF

Figure 3

Figure 2

Figure 1

Housing Conditions Animal Facility Closed Nest

A. CN male: Slight contralateral atrophy

B. CN male: moderate contralateral atrophy

C. CN female: absence of contralateral hipp.  

D. AF male: mild ipsilateral atrophy and contralateral infarct

E. AF female: ipsilateral atrophy and contralateral infarct