Ischemic stroke is a serious yet poorly studied problem in infants and children with a variety of acute and chronic illnesses. In spite of this, stroke in the immature brain has received little attention in basic science research. One reason for this is the lack of feasible animal models, which closely mimic the clinical picture of pediatric stroke. From the few studies that have been done in immature animal models, it appears that there are age-related differences in the mechanisms of focal ischemic injury in the brain. These mechanistic differences suggest that treatment strategies to reduce ischemic brain injury may need to be different in the immature compared to the mature brain. We recently developed a large animal model of ischemic stroke in two- to four-week-old infant piglets using a transorbital approach to produce photothrombotic occlusion of the middle cerebral artery. We measured acute changes in regional cerebral blood flow, examined histopathology at four hours after stroke onset and demonstrated that this method produces a moderate size infarct, which includes both cortical and subcortical tissue. The purpose of this exploratory project is to further establish this model of ischemic stroke in piglets at different stages of development for future investigations of age-related mechanisms of injury, repair and response to therapeutic interventions.
The specific aims are (1) to improve our method of producing stroke so that chronic survival is achieved in pigs at three stages of development, (2) to determine age-related differences in regional cerebral blood flow, size of the infarct, functional neurological outcome and magnetic resonance imaging twenty-fours hours and three, seven and thirty days after stroke onset, and (3) To explore whether age-related and time-dependent differences occur in three mechanisms of injury and repair after stroke, e.g., leukocyte accumulation, angiogenesis and apoptosis. This study is important because there are no large animal models of pediatric stroke, which include chronic survival to allow for investigations of age-related mechanisms of and recovery from ischemic brain injury. The results of these experiments will demonstrate whether, in fact, the immature brain recovers from stroke more rapidly and more completely than the adult brain and provide insight into which injury and repair mechanisms are responsible for the improved outcome from stroke during development.
| Kuluz, John W; Prado, Ricardo; He, Dansha et al. (2007) New pediatric model of ischemic stroke in infant piglets by photothrombosis: acute changes in cerebral blood flow, microvasculature, and early histopathology. Stroke 38:1932-7 |
| Huang, Tingting; He, Dansha; Kleiner, Gary et al. (2007) Neuron-like differentiation of adipose-derived stem cells from infant piglets in vitro. J Spinal Cord Med 30 Suppl 1:S35-40 |
