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Stem cell transplantation therapy has emerged as a potential treatment for ischemic stroke and other neurodegenerative diseases. Effective delivery of exogenous cells and homing of these cells to the lesion region, however, have been challenging issues that hinder the efficacy and efficiency of cell-based therapy. In the present investigation, we tested a delayed treatment of noninvasive and brain-targeted intranasal delivery of bone marrow mesenchymal stem cells (BMSCs) in a mouse focal cerebral ischemia model. The investigation tested the feasibility and effectiveness of intranasal delivery of BMSCs to the ischemic cortex. Hypoxia preconditioning (HP) of BMSCs was performed before transplantation in order to promote their survival, migration, and homing to the ischemic brain region after intranasal transplantation. Hoechst dye-labeled normoxic- or hypoxic-pretreated BMSCs (1 × 10 6 cells/animal) were delivered intranasally 24 h after stroke. Cells reached the ischemic cortex and deposited outside of vasculatures as early as 1.5 h after administration. HP-treated BMSCs (HP-BMSCs) showed a higher level of expression of proteins associated with migration, including CXC chemokine receptor type 4 (CXCR4), matrix metalloproteinase 2 (MMP-2), and MMP-9. HP-BMSCs exhibited enhanced migratory capacities in vitro and dramatically enhanced homing efficiency to the infarct cortex when compared with normoxic cultured BMSCs (N-BMSCs). Three days after transplantation and 4 days after stroke, both N-BMSCs and HP-BMSCs decreased cell death in the peri-infarct region; significant neuroprotection of reduced infarct volume was seen in mice that received HP-BMSCs. In adhesive removal test of sensorimotor functional assay performed 3 days after transplantation, HP-BMSC-treated mice performed significantly better than N-BMSC- and vehicle-treated animals. These data suggest that delayed intranasal administration of stem cells is feasible in the treatment of stroke and hypoxic preconditioning of transplanted cells, significantly enhances cell's homing to the ischemic region, and optimizes the therapeutic efficacy.

Current research is demonstrating the effectiveness of comprehensive reading instruction for individuals with intellectual disabilities (ID; Allor, Mathes, Roberts, Cheatham, & Champlin, 2010; Allor, Mathes, Roberts, Jones, & Champlin, 2010; Browder, Ahlgrim-Delzell, Courtade, Gibbs, & Flowers, 2008). One overarching finding from these studies is that intense amounts of repetition and practice on critical literacy skills are needed to produce meaningful gains. Providing intensive instruction in the school setting is extremely challenging. The purpose of this article is to describe the various strategies used in one research project to intensify early literacy instruction for students with ID, including methods for providing practice outside of teacher-led instruction. Specifically, we describe (a) key factors in planning intensive instruction, (b) general strategies for increasing intensity during teacher-led lessons, and (c) selecting and designing specific activities to increase intensity. (Contains 1 table and 9 figures.)

This longitudinal experimental study investigated the reading progress of students with IQs ranging from 40 to 69 (i.e., range for students with mild or moderate mental retardation or intellectual disabilities [ID]) across at least two academic years, as well as the effectiveness of a comprehensive reading intervention for these students across the same period of time. Participants were 59 elementary students who were randomly placed into treatment and contrast groups. Students in the treatment condition received daily, comprehensive reading instruction in small groups of 1-4 students for 40-50 minutes per session across two or three academic years. Measures of phonemic awareness, phonics, word recognition, comprehension, and oral language were included. Findings indicate that students with IQs in the ID range made significant progress on multiple standardized measures of reading. Furthermore, significant differences between the treatment group and contrast group were found on several measures, including progress-monitoring measures of phoneme segmentation, phonics, and oral reading fluency. Results demonstrate that, on average, students with ID, even those with IQs in the moderate range, learn basic reading skills given consistent, explicit, and comprehensive reading instruction across an extended period of time. (Contains 5 tables and 4 figures.)

The primary purpose of our research was to determine if a comprehensive, phonics-based, direct instruction reading program would be effective in teaching early reading and language skills to students with moderate intellectual disabilities (ID). Participants were 28 elementary students from 10 public schools in an urban school district and one urban private school who were randomly placed into treatment and contrast groups. Students in the treatment condition received daily, comprehensive reading instruction in small groups of 1-4 students for approximately 40 minutes per session. A broad array of measures was studied, including phonemic awareness, phonics, word recognition, comprehension, and oral language. Means favored the intervention group on all measures, with moderate to strong effect sizes. Statistically significant differences were found on most measures, including phonemic awareness, phonics, vocabulary, and comprehension. These findings demonstrated that students with moderate ID can learn basic reading skills given consistent, explicit, and comprehensive reading instruction across an extended period of time. (Contains 6 tables and 2 figures.)

Jacob, Bart, and Carl are children with intellectual disabilities (ID; i.e., mental retardation) who experience significant difficulty in learning to read. In the past, most research about reading methods for students with ID focused on teaching students to memorize sight words, a method that is clearly effective. Memorization of sight words is definitely useful and is an important part of reading; however, reading is more than memorizing sight words. Educators often assume that children with ID are not capable of learning to read beyond memorizing a limited corpus of sight words. The result is that educators often make little effort to teach students with ID to become fully literate, and only one in five children with mild or moderate ID achieves even minimal literacy skills. This article presents the stories of Jacob, Bart, and Carl which highlight both the potential for students with ID to become more fully developed readers and the challenges that they face during research-based reading instruction. Three centers, recently funded by the Institute of Education Sciences, are conducting studies to explore methods for teaching students with ID to read. Jacob, Bart, and Carl have been participating in a study that seeks to determine whether methods that are effective with at-risk students with average IQs are also effective for students like Jacob, Bart, and Carl. All three made great strides in their reading abilities because of intense, individualized daily instruction. All three made important progress on phonemic awareness and basic phonics skills. They are currently able to read very simple text independently and are on their way to becoming more fluent readers. However, achieving this success has taken a long time and has required persistent, careful instruction tailored to individual student progress and needs. Common instructional needs included struggles with memory, application of skills, mastery, and language. Behaviorally, modifications increased attention, promoted positive peer relationships, and maximized compliance. Responding effectively to individual challenges required the work of the entire team of educators, coaches, and researchers. With daily implementation of the research-based curriculum tailored to individual progress and needs, the students continued to grow toward acquiring first-grade-level benchmarks. The stories of these students confirm that teachers need to maintain high expectations and continue to provide high-quality research-based reading instruction for all students. Current research demonstrates the potential for reading ability in all students, including those with ID. (Contains 1 figure.)