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 glucose supply to the brain of an otherwise healthy neonate around the time of delivery resulting in global ischemic brain injury.
GAP: Therapeutic hypothermia (HT), our current standard of care, is ineffective in severe HII, whereas our work demonstrates that human neural stem cells (hNSCs) salvage injured brain tissue leading to improved histologic and behavioral outcomes in an animal model of HII. We suggest that combining HT and hNSC therapies in an animal model seems 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 histologic and behavior 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 the Rice Vannucci Method – a well-studied and well-accepted procedure to induce hypoxic brain injury in an animal model. After first establishing the baseline impact of HT on experimental HII, we will then assess the impact of merging hNSC administration with HT before ultimately determining the optimal timing of combination therapy using MRI, histology, and standardized behavioral metrics.
IMPACT: It will help us understand the mechanism by which our current SOC may be effective (as well as the reason for its lack of efficacy in severe cases). It will immediately standardize MRI as a non-invasive modality for HII scoring and aid in prognosis. Most importantly, it will lay a concrete groundwork for the 1st clinical trial using hNSCs for neuroprotection against perinatal HII.