ABSTRACT
Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity.
Subject(s)
Axonal Transport/physiology , Brain Ischemia/surgery , Cerebral Cortex/cytology , Neural Stem Cells , Neuronal Plasticity/physiology , Analysis of Variance , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Infarction/etiology , Brain Infarction/pathology , Brain Ischemia/complications , Cell Survival , Cells, Cultured , Corpus Callosum/pathology , Dendrites/physiology , Dextrans/metabolism , Disease Models, Animal , Fetus , Gene Expression Regulation , Humans , Male , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/physiology , Neural Stem Cells/transplantation , Psychomotor Performance/physiology , RNA, Messenger/metabolism , Rats , Rats, Nude , Rats, Sprague-Dawley , Time Factors , Vibrissae/innervationABSTRACT
OBJECTIVES: Prenatal infectious diseases are a major cause of mortality and morbidity among newborns, but many are preventable with proper maternal screening and treatment. METHODS; Adherence to prenatal infectious disease screening guidelines and demographic factors that influence adherence were determined utilizing existing data on 1837 live births from 1999-2003. RESULTS: We found higher rates of testing for syphilis (94.54%), rubella (92.69%) and hepatitis B (94.23%) than for HIV (73.82%) and GBS (69.05%). Adherence to testing guidelines varied by both disease and maternal factors. Lack of insurance, geographic location, inadequate prenatal care and incarceration were the main maternal factors associated with lack of testing. CONCLUSIONS: Disease screening rates may be improved by reducing socioeconomic barriers to prenatal testing, supporting access to insurance, eliminating provider biases and providing adequate prenatal care.