Repository logo

Department of Allied Health and Human Performance

Permanent link for this collection

https://hdl.handle.net/20.500.14078/26

Browse

Browsing Department of Allied Health and Human Performance by Subject "cerebral ischemia"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Intracerebral stem cell transplantation in experimental stroke models
    (2009) Hicks, Anna
    Cerebral ischemia causes severe functional deficits leaving majority of patients with permanent disabilities. Physical rehabilitation remains the only widely accessible therapy that facilitates functional recovery. Stem cells are suggested to possess the ability to replace lost cells and tissue and thus may enhance functional recovery after stroke. Indeed, according to previous studies stem cells moderately facilitated recovery in animal models of stroke. We used rat models of focal cerebral ischemia and intracerebral transplantation of stem cells. Cells were injected into close proximity of the injured brain tissue one week after the stroke. The animals were tested in sensorimotor tests in various timepoints to quantify functional recovery. We transplanted neurospheres isolated from subventricular zone (SVZ) of mice or human neuronal progenitor cells (hNPC) derived from human embryonic stem cells (hESC). Survival, migration and differentiation of stem cells were examined using immunohistochemistry, immunofluorescence techniques, stereology and confocal microscopy. In addition, the effects of enriched environment (EE) rehabilitation and running exercise combined with stem cell therapy were examined. Animals received immunosuppressive drug to minimize rejection of the transplants. Results show that the combination therapy of rehabilitation and SVZ stem cell transplantation resulted into enhanced migration of stem cells and better functional outcome within first weeks after the ischemic insult. Longterm studies of SVZ cells revealed that the majority of transplanted cells disappeared after the first month and the remaining cells differentiated into glial cells within two and three months after the transplantation. Transplantation of hESC-derived hNPCs resulted into modest functional recovery. Again the survival of cells was minimal. Majority of hNPCs expressed precursor marker nestin, however some of the cells had neuronal phenotypes two months after the transplantation. In longterm studies the EE rehabilitation had no effect on the transplanted SVZ/hNPC cells. We found sustained activation of immune cells in the brains that had received cell transplantation. In conclusion, stem cell therapy supports endogenous brain repair mechanisms during the first weeks after transplantation, and EE rehabilitation supports the beneficial effects of stem cells. However, the cells fail to survive for protracted time periods after intracerebral transplantation. It is crucial to identify the factors restricting stem cell survival and migration in stroke injured cerebral microenvironment before the true effects of transplantation therapy can be measured.
  • Thumbnail Image
    Item
    Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery
    (2009) Rissanen, Anna; Lappalainen, Riikka S.; Narkilahti, Susanna; Suuronen, Riitta; Corbett, Dale; Sivenius, Juhani; Hovatta, Outi; Jolkkonen, Jukka
    Cortical stem cell transplantation may help replace lost brain cells after stroke and improve the functional outcome. In this study, we transplanted human embryonic stem cell (hESC)-derived neural precursor cells (hNPCs) or vehicle into the cortex of rats after permanent distal middle cerebral artery occlusion (dMCAO) or sham-operation, and followed functional recovery in the cylinder and staircase tests. The hNPCs were examined prior to transplantation, and they expressed neuroectodermal markers but not markers for undifferentiated hESCs or non-neural cells. The rats were housed in either enriched environment or standard cages to examine the effects of additive rehabilitative therapy. In the behavioral tests dMCAO groups showed significant impairments compared with sham group before transplantation. Vehicle groups remained significantly impaired in the cylinder test 1 and 2 months after vehicle injection, whereas hNPC transplanted groups did not differ from the sham group. Rehabilitation or hNPC transplantation had no effect on reaching ability measured in the staircase test, and no differences were found in the cortical infarct volumes. After 2 months we measured cell survival and differentiation in vivo using stereology and confocal microscopy. Housing had no effect on cell survival or differentiation. The majority of the transplanted hNPCs were positive for the neural precursor marker nestin. A portion of transplanted cells expressed neuronal markers 2 months after transplantation, whereas only a few cells co-localized with astroglial or oligodendrocyte markers. In conclusion, hESC-derived neural precursor transplants provided some improvement in sensorimotor function after dMCAO, but did not restore more complicated sensorimotor functions.