Despite decades of research into the pathophysiology of hypoxic-ischemic brain injury and neuroprotection, effective therapy remains elusive and our clinical role after such an injury is largely supportive. More frustrating is the number of promising therapies that are effective in cell culture and animal models, but have subsequently failed to demonstrate benefit in clinical trials. The heterogeneity of injury and physiology, and the uncertain therapeutic window, are barriers to the translation of neuroprotective interventions. Additionally, pediatric brain injury studies must account for age related differences in cerebro-vascular physiology and susceptibility to brain ischemia, requiring prohibitively large multicenter trials to assess clinical benefit.
In an effort to overcome these barriers to translating neuroprotective interventions, we use small animal MRI to identify biomarkers of injury and therapeutic effect in animal models of pediatric cerebral ischemia. A combination of real-time imaging, conventional longitudinal imaging, and rodent behavioral testing is used to comprehensively assess neurodevelopmental differences in the physiology of ischemia and reperfusion, and the response to neuroprotective interventions. We have worked closely with the Sun Lab on their investigation into the role of the sodium/ hydrogen membrane ion exchanger (NHE1) in cerebral ischemia. We recently used T2 and Diffusion Weighted MRI to establish that genetic and chemical inhibition of NHE1 is neuroprotective in a mouse model of transient focal cerebral ischemia. Additionally, this work suggests that the size of the lesion seen on Diffusion Weighted images may be used as a biomarker of neuroprotection as early as one hour after reperfusion.
By identifying MRI biomarkers in animal models of pediatric brain injury, we hope to provide a means for selecting the patients most likely to benefit from a particular neuroprotective intervention in subsequent clinical trials. Basing patient selection on the physiologic target of therapy rather than simply the disease state will reduce the sample size needed, increase the likelihood of observing a drug effect, and facilitate the translation of promising neuroprotective interventions into clinical use.
The Midwest Society for Pediatric Research (MSPR) held its annual meeting at Lurie Children’s Hospital last week and the UW-Madison Department of Pediatrics was well represented. Members from all levels of the UW-Madison Department of …October 30, 2019
Severe traumatic brain injury (TBI) is the leading cause of death and long-term disability in children, affecting over 30,000 children each year. Although clinicians use advanced neuroimaging tools such as magnetic resonance imaging (MRI) to …May 12, 2016
Peter Ferrazzano, MD, was recently awarded an R01 grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH-NINDS) for his proposal entitled, “MRI Markers of Functional Outcome after Severe Pediatric TBI”. …May 1, 2016
Congratulations to the following students and their mentors who have been awarded 2015-2016 Wisconsin Hilldale Undergraduate/Faculty Research Fellowships. Award recipients receive $3,000 and faculty mentors $500 to sponsor a research project that will be presented …June 1, 2015
Peter Ferrazzano, MD, Receives NIH-NINDS Mentored Clinical Scientist Research Career Development Award
Congratulations to Peter Ferrazzano, MD, on receiving a National Institutes of Health – National Institute of Neurological Disorders and Stroke (NIH-NINDS) Mentored Clinical Scientist Research Career Development Award (K08) for his project entitled, “Age-dependent microglial …July 1, 2013
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