Stem cells in addition to hypothermia for neuroprotection in perinatal hypoxic-ischemic brain injury
Janessa Law, MD
BACKGROUND: Perinatal hypoxic ischemic injury (HII) is due to the unpredictable and unpreventable loss of blood and oxygen supply to the brain of an otherwise healthy neonate around the time of delivery resulting in global brain injury. GAP: Therapeutic hypothermia (HT) is the current standard of care for HII; however, it has limited utility for those infants with severe HII. Prior work demonstrates that human neural stem cells (hNSCs) salvage injured brain tissue leading to improved imaging, histologic, and behavioral outcomes in an animal model of HII. We suggest that combining HT and hNSC therapies appears feasible and must be completed prior to progression to human studies. HYPOTHESIS: We hypothesize that hNSCs will work synergistically with HT by providing neuroprotection via different yet complementary mechanisms to improve imaging, histologic, and behavioral outcomes in a rat model of HII. METHODS: To approximate a term human neonate, developmentally equivalent ten day old rat pups will be subjected to HII via unilateral common carotid artery occlusion followed by hypoxia - a well-studied and well-accepted procedure to induce hypoxic brain injury in an animal model. We will assess the interaction between HT and hNSC transplantation 3 days post-injury by MRI, histology, and standardized behavioral metrics. RESULTS: Pending IMPACT: This study may support early MRI as a non-invasive modality for HII scoring to aid in optimal treatment and prognosis. Most importantly, it will lay a concrete groundwork for the 1st clinical trial using hNSCs for neuroprotection against perinatal HII.