Introduction: Traumatic brain injury (TBI) is the leading cause of death and severe morbidity for healthy-born infants. No multi-center intervention trials have been conducted for infants with TBI. Currently, the primary treatment for TBI in children is supportive; no targeted intervention exists to promote recovery. The developing infant brain has both unique potential for repair and response to injury, and both vary with maturation. We developed a pre-clinical model of moderate to severe TBI in infants to better characterize the extent of injury and neuropathology, with the goal of directing restorative therapy.

Methods: Under anesthesia, rats on postnatal day 12 (P12) underwent left parietal craniotomy. Heads were held in position and an air-powered piston delivered a controlled cortical parietal impact (CCI) of 0.6mm deflection. Sham animals underwent equal time anesthesia with a scalp incision only. Animals underwent computerized treadmill gait analysis at age P25-26. Specimens were collected at multiple post-injury time points for magnetic-resonance imaging (MRI) and biomarker analysis using multi-array electrochemiluminescence detection.

Results: Thirty-two animals (20 CCI, 12 sham) were included. Mortality in CCI was 5percent, zero in sham. Digigait analysis showed a functional gait abnormality with both coordination and stability difficulties in CCI right fore and hind-limbs. Serum analysis revealed elevated TNF-a (tumor-necrosis-factor-alpha) and CXCL1 (CXC-chemokine-ligand 1) levels in CCI (nequal6) versus sham animals (nequal4, both p lessthan 0.01), and reduction of IL-6 (interleukin-6, p equals0.02) at 3 days post-injury. MRI analysis is pending.

Conclusions: We developed a novel, clinically relevant model to investigate targeted-therapies in infantile moderate to severe TBI. Injured animals demonstrated a reproducible injury that resembles the subacute clinical course of infantile TBI. Serum biomarkers revealed increased levels of TNFa and CXCL1, markers of glial inflammation. This preclinical model will facilitate testing of neuroreparative strategies in this previously-neglected population.

Patient Care: This model will help to elucidate the unique characteristics of infantile TBI, and potentially identify populations that may benefit from restorative therapies.

Learning Objectives: By the conclusion of this session participants should be able to 1) Describe the unique characteristics of TBI in the infant population 2) Discuss, in small groups the neuropathology of TBI in infants 3) Identify potential treatment mechanisms for this population.

References: Shein, SL, Bell, MJ, Kochanek, PM, Tyler-Kabara, EC, Wisniewski, SR, Feldman, K, Makoroff, K, Scribano, PV, and Berger, RP. Risk factors for mortality in children with abusive head trauma J Pediatr, 2012. 161(4): p. 716-722 e1 Li, L and Liu, J. The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review Dev Med Child Neurol, 2013. 55(1): p. 37-45 Li, L and Liu, J. The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review Dev Med Child Neurol, 2013. 55(1): p. 37-45