28 - Motor Deficits Following Neonatal Hypoxic-Ischemic Brain Injury

Motor deficits following neonatal brain injury are common, yet often underreported and not fully understood. From cerebral palsy to subtle deficits in motor planning and learning, hypoxia-ischemia’s outcomes can have a detrimental impact on the lives of affected children. Rodent models of motor deficits in neonatal hypoxia-ischemia (HI) allow improved understanding of the underlying mechanisms of motor deficits and testing of novel neuroprotective strategies.

Objective:

To test complex motor performance and learning in a mouse model of neonatal HI.

Design/Methods:

We induce HI (unilateral carotid ligation+60 min 8%O2) or sham procedure (incision + anesthesia only) on postnatal day (p)10 c57 mice. Complex motor performance and learning on p28-p33 was assessed using the accelerating rotarod task and complex running wheel task.

For rotarod, mice are placed on the rotating cylinders, speed accelerates gradually (0.4 to 4.0 rpm). Mice undergo 3 training days of 10 trials/day. Latency to fall is compared across trials within day and across days to assess short and long-term performance.

For complex running wheel, mice are given continuous access to a simple running wheel (gross motor test) followed by a complex wheel (complex motor test, a pattern of spokes removed) x4 days each. Average time/wheel rotation is measured across days for each portion of the task.

Results:

We observed a significant difference in rotarod performance on days 1, 2 and 3 between HI and sham groups (n=19, day1 p=0.0146, day2 p=0.0088, day3 p=0.0347; unpaired t-test). Improvement across days was significantly greater in sham mice (n=7, p=0.0046; linear regression) compared to HI (n=12, p= 0.1566). [Fig1A]

There were no differences in simple running wheel performance between HI and sham (n=5/group, day 1 p=0.7, day 4 p=0.6; unpaired t-test) [Fig1B]. On the complex running wheel, HI mice exhibited slower performance than sham on day 1&2 (n=5/group, day 1 p=0.02), but by day 4 were similar (p=0.67). [Fig1C]

Conclusion(s):

Overall, we demonstrate that young adult mice exposed to HI exhibit significant deficits in complex motor performance compared to sham. HI mice do not show deficits in gross motor performance; however, more subtle deficits are present in complex motor performance and learning. This neonatal HI model exhibits translatable deficits in complex motor performance and learning that are relevant to findings in humans that experience neonatal HI. Ongoing work examines changes in the motor circuit in this model to further understand underlying mechanisms of motor differences in this population.