Stem cell therapies hold great promise for diseases such as stroke, where few effective treatment options exist. Clinical translation of experimental stem cell therapies requires the ability to monitor delivery and behaviour of cells non-invasively in-vivo with clinical imaging modalities such as MRI. This thesis presents the translation of established methods for labelling and imaging stem cells with specialized MRI systems to a more clinically relevant setting. A methodology for harvesting and labelling a cell population containing stem cells with iron oxide for detection with a clinical MRI system is presented and single cell detection is demonstrated in-vitro. The feasibility of detecting iron oxide labelled stem cells intravenously delivered in a rat model of stroke is tested. Results demonstrate that while MRI is highly sensitive to the presence and distribution of iron oxide containing cells in-vivo the true origin of these cells remains ambiguous with the current methodology.

Survivors of subarachnoid hemorrhage (SAH) often have learning and memory deficits. This study tested the hypothesis that SAH in rats is associated with similar deficits and that they are due to neuronal injury in the hippocampus. SAH was induced in rats. Behaviour was investigated in the Morris water maze and brain injury by microscopy. Rats with SAH had deficits in spatial learning and working memory and had significantly more fluoro-Jade- and TUNEL-positive neurons in the hippocampus, cerebral cortex and cerebellum. Microthromboemboli in microvessels were more frequent in brains of rats with SAH and deficits there was vasospasm of the anterior and middle cerebral arteries. The amount of cell death in the hippocampus did not appear to be sufficient to cause the observed in the Morris water maze. This suggests that other factors such as dysfunction of neurotransmission or other pathology in hippocampal pathways might contribute to the impairment.

Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from rupture of a blood vessel in the brain. Tissue inside the hematoma is irreversibly damaged soon after ICH onset and when this thesis research began, there was a dearth of information regarding pathological changes outside the hematoma. Inflammation is often proposed as a mechanism of injury, but very little information was available to show that inflammatory cells were in the right place at the right time to cause secondary brain injury. Using the collagenase-induced model of ICH, this work sought to better define spatial and temporal relationships between secondary brain injury and the inflammatory response after ICH. To test the hypothesis that reducing inflammation can protect the brain from secondary injury, minocycline, an antibiotic with established anti-inflammatory effects, was administered 6 hours after ICH onset. A small number of neurons die in the parenchyma bordering the hematoma between 6 hours and 3 days after ICH onset. This area was not associated with neutrophil infiltration, and most activated microglia/macrophages did not accumulate until after most neuron death had occurred. Despite a pronounced microglial response and prolonged increase in expression of many inflammatory genes, including complement receptor-3, interleukin-1 beta, interleukin-6, and interleukin-1 converting enzyme, no dying neurons were observed further outside the hematoma at any time. Interestingly, less early neuron death was observed in aged than in young animals, without a concomitant difference in the amount of tissue lost at 28 days. However, aged animals had less early microglial activation and a larger residual lesion, which might have resulted from impaired phagocytosis by activated microglia/macrophages. Minocycline was less effective in reducing microglial activation in aged animals, and did not reduce neuron death in either young or aged animals. Edema and BBB disruption was associated with degradation of the basal lamina protein, collagen type IV, and that damaged vessels are associated with tumor necrosis factor-alpha (TNFα)-positive neutrophils and active matrix metalloprotease-12 (MMP-12), all of which were reduced by delayed minocycline treatment. In contrast to ischemic stroke, there is a limited ‘penumbra’ outside the hematoma. Nevertheless, BBB damage in this region appears to be a potential target for protection. Furthermore, the prominent inflammatory response that continues for days after ICH does not appear to be associated with damage to other areas of the brain. Minocycline appears to protect the BBB by reducing neutrophil infiltration and the MMP-12 mediated basal lamina degradation. Future studies should investigate other targets for protection (i.e., white matter injury), and seek drugs that modulate the inflammatory response in aged animals and promote lesion resolution.

Hyperthermia worsens outcome after ischemia. While it seems reasonable that hyperthermia would also worsen outcome after intracerebral hemorrhage (ICH), clinical studies attempting to find a causative relationship between hyperthermia and outcome have been inconclusive. We induced ICH with an injection of autologous whole blood (100 l) immediately followed by 3 hours of hyperthermia (HYPER; 39C) or normothermia (NORMO; 37C). Surprisingly, hyperthermia reduced edema at 72 hours, and improved outcome on day 3 post-ICH. There were no behavioural differences at later time points (day 11 and 32 post-ICH) and no difference in lesion volume (NORMO 14.0 mm3, HYPER: 14.5 mm3). Overall, this study does not support the hypothesis that mild, transient hyperthermia worsens outcome after ICH. Further research is needed to determine if more severe or prolonged hyperthermia worsens outcome, or if the cause of hyperthermia (e.g. infection) is important.

<p>Lack of knowledge about stroke in general and specific knowledge of the risk factors, signs, and symptoms of stroke results in the late presentation of patients at hospital. The aim of this study was to determine the knowledge of stroke among hypertensive patients in the Tanga region of Tanzania. To investigate this, a cross-sectional survey using a quantitative research design was used.</p>

No description available.

Diffusion Tensor Magnetic Resonance Imaging (DTI) is a recently-developed technique that can image in vivo the white matter pathways of the central nervous system. This study used 12-direction diffusion-weighted MRI data from nine stroke patients acquired as part of a three-year stroke rehabilitation study coordinated by the Movement Neuroscience Laboratory at the University of Auckland. DTI was used to investigate corticospinal connectivity. From the FA maps, it is found that in those patients whose motor connectivity has been compromised by the stroke to the extent that no motor evoked potential (MEP) can be elicited from a selected affected muscle group, the asymmetry in mean FA values in the posterior limbs of the internal capsules (PLICs) is correlated with functional recovery as measured by the Fugl-Meyer clinical score. Using probabilistic tractography in the contralesional hemisphere produced CST location and somatotopy results that were consistent with those of previous studies. However, in the ipsilesional hemisphere, connectivity results were highly variable. A measure of change in symmetry of mean connectivity is found to correlate with functional recovery as measured by change in FM score. This supports previous work which has correlated CST integrity and functional improvement and it supports the theory that functional recovery after stroke depends on the extent to which motor CNS symmetry can be regained in the new post-stroke architecture. It also suggests that the movement of the fMRI activations occurs in such a way as to make the most of the preserved white matter connectivity.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet , 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2006. / Härtill 5 uppsatser.