ABSTRACT
BACKGROUND: Studies have demonstrated improvements in arm motor function after constraint-induced (CI) therapy. Few studies of CI therapy for lower extremity conditions have been done. Our purpose was to evaluate the effect of modified CI therapy for the lower extremity in terms of motor control in elderly persons with chronic stroke. METHOD: A single-subject experimental AB design was used, with 3 months of follow-up. The A phase consisted of a baseline period of 2 weeks with 6 measurements, and the B phase was a 4-week intervention with 8 measurements. Two men and 1 woman were included. The intervention consisted of intensive rehabilitation of the affected leg for 2 hours each weekday. A whole-leg orthosis was used to immobilize the nonaffected leg. The following tests were conducted: a step test for dynamic balance, Fugl-Meyer assessment for lower-extremity motor function, the Timed Up and Go test for mobility, and the 6-minute and 10-meter walk tests for walking ability. Statistical significance was analyzed by using Shewhart charts with a 2-standard deviation band method. RESULTS: A positive change was observed in 14 of 18 variables. Significant improvements existed in 7 of the 14 positively changed variables. Positive changes remained in 13 of 14 variables at the 3-month follow-up evaluation. CONCLUSION: Modified CI therapy may result in positive changes in balance and motor function in elderly persons with chronic stroke.
Subject(s)
Lower Extremity/physiopathology , Physical Therapy Modalities , Stroke Rehabilitation , Aged , Chronic Disease , Data Interpretation, Statistical , Exercise Therapy , Female , Humans , Male , Postural Balance , Psychomotor Performance , Recovery of Function , Stroke/physiopathology , Treatment Outcome , WalkingABSTRACT
Several different receptor molecules act in concert to regulate cell adhesion. Among these are cell-surface proteoglycans and integrins, which collaborate extensively in mediating binding of cells to extracellular matrix molecules fibronectin and vitronectin. However, very little is known about possible functional synergism between proteoglycans and integrins during adhesion of cells to collagen, although collagen is the most abundant protein in the human body. Here we show that cell-surface heparan sulphate proteoglycans (HSPGs) support integrin alpha2beta1-mediated adhesion to collagen. Cells made devoid of HSPGs either by genetic means or by enzymatic digestions were unable to adhere to collagen via alpha2beta1 integrin. HSPG-deficient cells also displayed impaired spreading and actin organization on collagen. Among different HSPG molecules syndecan-1 was found to play an important role in supporting alpha2beta1 integrin-mediated adhesion. Using overexpression and knock-down experiments we demonstrated that syndecan-1, but not syndecan-2 or -4, enhanced binding of alpha2beta1 to collagen. Moreover, syndecan-1 co-localized with alpha2beta1 integrin and contributed to proper organization of cortical actin. Finally, crosstalk between syndecan-1 and alpha2beta1 integrin was found to enhance the transcription of matrix metalloproteinase-1 in response to collagen binding. Our findings thus suggest that a previously unknown link between integrin alpha2beta1 and syndecan-1 is important in regulating cell adhesion to collagen and in triggering integrin downstream signalling.
Subject(s)
Collagen/metabolism , Heparan Sulfate Proteoglycans/physiology , Integrin alpha2beta1/metabolism , Syndecan-1/metabolism , Actins/metabolism , Animals , CHO Cells , Cell Adhesion/physiology , Cell Line , Cricetinae , Cricetulus , Flow Cytometry , Fluorescent Antibody Technique , Heparan Sulfate Proteoglycans/pharmacology , Integrin alpha2beta1/drug effects , Integrin alpha2beta1/genetics , Mutation , Peptides/genetics , Peptides/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Up-RegulationABSTRACT
Dynamic turnover of integrin cell adhesion molecules to and from the cell surface is central to cell migration. We report for the first time an association between integrins and Rab proteins, which are small GTPases involved in the traffic of endocytotic vesicles. Rab21 (and Rab5) associate with the cytoplasmic domains of alpha-integrin chains, and their expression influences the endo/exocytic traffic of integrins. This function of Rab21 is dependent on its GTP/GDP cycle and proper membrane targeting. Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, whereas its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone. Finally, overexpression of Rab21 fails to induce cell adhesion via an integrin point mutant deficient in Rab21 association. These data provide mechanistic insight into how integrins are targeted to intracellular compartments and how their traffic regulates cell adhesion.
