Comparative Analysis of Neonatal versus Adult Brain in Unilateral Brain Injury Mice Model Revealing Genes Involved in High Compensatory Motor Functional Recovery Mechanism

Previously, while studying the development, especially of corticospinal neurons, it was concluded that the main compensatory mechanism after unilateral brain injury in rat at neonatal stage was due to in part by nonlesioned ipsilateral corticospinal neurons that escaped selection by axonal elimination or neuronal apoptosis (Yoshikawa et al., 2011, Dev Neuroscience). However, above result suggesting compensatory mechanism in neonate brain could not be correlated with high functional recovery. Therefore, we asked - what is the difference among neonate and adult in context of functional recovery and mechanism/s therein, especially focused on the corticospinal neurons? Toward this goal, in the present study, we have utilized a unilateral brain injury mice model and compared motor functional recovery mechanism post-neonatal brain injury (hereafter termed, NBI) with adult brain injury (hereafter termed, ABI). Three analyses were perfomed: i) quantitative behavioral analysis of the forelimb movements using the ladder walking test, where the corticospinal system has been suggested to play an important role ii) a neuroanatomical retrogradely tracing analysis of unlesioned side corticospinal neurons; and iii) differentially global gene expressions profiling in the unlesioned-side neocortex (rostral from bregma) in NBI and ABI using a high-throughput DNA microarray approach on a 8x60 K whole genome Agilent DNA chip using a two-color (Cy3/Cy5) dye-swap approach. Behavioral data confirmed the higher recovery ability in NBI over ABI is related to non-lesional frontal neocoetex including rostral caudal forelimb area. With a overall aim to unravel the underlying molecular events, in the present study a first inventory of the differential expressed gene expressions genome-wide in the NBI and ABI model mice has been provided. The neonatal (n=20) and adult (n=12) left hemidecortication animals were made to perform the ladder rung walking test after 4, 8, and 12 weeks of lesion creation. The control animals (n=9) did the same test postnatal 8-12 weeks. The hemidecortication animal model was perfomed at postnatal day 7 (NBI group) and postnatal 8-12 weeks (ABI group). In the NBI and ABI groups, we decided to aspirate area of left cerebral cortex including the sensorimotor cortex (SMC). In order to confirm different motor functional mechanism between NBI and ABI, the right side neocortex (rostral from bregma) was individually ground to a very fine powder with liquid N2 t prepare teh samples for DNA microarray analysis.