411 - Behavioral Abnormalities and Their Mechanisms in a Model of Bronchopulmonary Dysplasia

Poster Number: 411
Publication Number: 411.237

Sakiko Suzuki, Nagoya University, Nagoya, Aichi, Japan; Yoshiaki Sato, Nagoya University Hospital, Nagoya, Aichi, Japan; Ryoko Goto, Nagoya University, Nagoya city, Aichi, Japan; Yukina Takamoto, Nagoya university, Nagoya-city, Aichi, Japan; Takahiro Kanzawa, Nagoya University, Nagoya, Aichi, Japan; Kazuto Ueda, Nagoya University Hospital, Nagoya, Aichi, Japan; Ryosuke Miura, Nagoya University, NAgoya, Aichi, Japan; Yoshiyuki Takahashi, Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Masahiro Hayakawa, Nagoya University Hospital, Nagoya, Aichi, Japan

Background: Bronchopulmonary dysplasia (BPD) is one of the most serious complications in preterm infants, affecting not only respiratory function but also neurological prognosis. However, the detailed mechanism by which BPD leads to brain injury remains unclear.

Objective: In the present study, we conducted various behavioral and histological evaluations, using a model of BPD induced by exposure to hyperoxia, to reveal the effect of BPD on the brain and its underlying mechanism.

Design/Methods: Neonatal pups were exposed to 83% oxygen from postnatal day 1 (P1) to postnatal day 15 (P15) to create a BPD animal model. Neonatal reflexes were tested using the negative geotaxis test from P8 to P16, and behavioral evaluations including horizontal ladder, rota rod, social interaction, and shuttle avoidance tests were performed between the 5th and 8th week of age. Histological evaluations of the cerebrum and cerebellum in the acute phase (on P7, P10, and P14), and chronic phase (at the 4th and 8th weeks of age) were performed.

Results: In the negative geotaxis test, the scores of the BPD group were significantly lower compared to the Sham group on P8, P14, and P15 (p < 0.05 on P8, p < 0.01 on P14 and P15). In the evaluation of motor deficit, the horizontal ladder test revealed significantly higher scores (more deficit) in the BPD group than those in the Sham group (p < 0.05). In the rota rod test, the latency to fall also tended to be shorter in the BPD group compared to the Sham group. In addition, the shuttle avoidance test for evaluation of learning impairment revealed significantly lower avoidance rates in the BPD group compared to the Sham group (p < 0.05). Moreover, in the social interaction test, the social interaction times were significantly shorter in the BPD group compared to the Sham group (p < 0.01). Histological evaluation showed greater thickening of the external granular layer in the cerebellar tissue of the BPD group compared to the Sham group (p < 0.05 on P7) in the acute phase, and reductions in the volume of the entire cerebrum and corpus callosum of the BPD group compared to the Sham group in the chronic phase.Conclusion(s): The results indicated that the model of BPD with exposure to hyperoxia indicated the development of sensory or proprioceptive dysfunction, along with motor and cognitive disabilities, and these abnormalities might be related to delayed cell migration in the cerebellum and abnormal development of the cerebrum.