Saudi Cultural Missions Theses & Dissertations
Permanent URI for this communityhttps://drepo.sdl.edu.sa/handle/20.500.14154/10
Browse
4 results
Search Results
Item Restricted Investigation of a Low Sulphated Heparan Sulphate Mimetic for CNS Repair in an Animal Model of Demyelination(University of Glasgow, 2024-08-05) Zubair, Jood; Lindsay, SusanCentral nervous system (CNS) diseases, which include multiple sclerosis (MS), pose significant challenges due to their complex pathology and impact on patient quality of life. This investigation assesses the therapeutic potential of LS-mHep7, a low-sulphated heparan sulphate mimetic, using the cuprizone-induced demyelination model, which mimics MS characteristics such as demyelination, astrocyte reactivity, and microglia activation. Mice received cuprizone diet for five weeks to induce demyelination, followed by a two-week treatment with LS-mHep7 or PBS. Immunohistochemical analysis of brain sections was performed using markers for myelin (PLP), astrocytes (GFAP), and microglia (IBA-1). In vitro experiments investigated the effects of LS-mHep7 on microglia morphology, proliferation, and reactivity, using GM-CSF as an activator. In vivo experiments revealed that LS-mHep7 did not significantly improved PLP staining in the corpus callosum compared to PBS-treated mice, indicating that the treatment did not improve remyelination within the twoweek timeframe. Moreover, LS-mHep7 did not significantly reduce astrocyte reactivity or microglia activation, as seen by GFAP and IBA-1 staining. In vitro experiments demonstrated that LS-mHep7 had no significant effect on microglial morphology or GM-CSF-induced reactivity. While LS-mHep7 showed potential for promoting remyelination previously in vitro, it did not have any effect in this in vivo investigation nor did it effect glial reactivity. More accurate results may be obtained by optimizing approaches to treatment and using alternative quantification methods. Future studies should investigate different dosages, treatment durations, and combination therapies to improve LS-mHep7's efficacy in CNS repair.10 0Item Restricted Olfactory Mesenchymal Stromal Cells: A Potential Therapeutic Approach for Central Nervous System Repair(University of Glasgow, 2024) Alamoudi, Wesal; Lindsay, SusanMultiple sclerosis (MS) is an autoimmune mediated demyelinating disease that occurs in the central nervous system (CNS). The loss of myelin creates a disturbance in the flow of the electrical signals in the nerve cells leading to a range of neurological symptoms. Currently, only the inflammatory component is managed with no cure for the disease itself. A possible therapeutic approach is stem-cell based therapies. Bone marrow derived mesenchymal stromal cells (BM-MSCs) have been considered, but have limitations in promoting myelination. A newer approach is to utilize olfactory mucosa-derived MSCs (OM-MSCs) since they exist in a neurogenetic niche and provide more myelination enhancement. In this investigation, an in vitro and in vivo comparison of BM-MSCs and OM-MSCs was undertaken. OM-MSC condition media (CM) showed significant outcomes regarding OPC differentiation and the promotion of myelination in vitro. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), OM-MSC transplanted animals had reduced inflammation, myelin loss and astrocyte reactivity unlike BM-MSCs. This study also investigated the effect of OM-MSC-CM on IL-16-induced astrocyte reactivity in vitro. However, there was no significant effect. Taken together, our findings suggest that OM-MSCs should be considered as a therapeutic candidate to promote myelin repair in MS.16 0Item Restricted Medication Choice and Management Decision Making Considering Family Planning for Women Living with Multiple Sclerosis.(University College London, 2023-11-28) Almouzain, Lubna; Hamilton, Fiona; Stevenson, Fiona; Chard, DeclanBackground Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disorder that affects women more than men. Most women are diagnosed during their childbearing years when they have not yet completed their family. Starting disease modifying drugs (DMDs) is vital in some MS cases to control the disease and prevent further disability. Choosing whether to start treatment or to complete their family first, or choosing to continue, stop, or switch treatment to conceive are all tricky decisions for both healthcare providers and women with MS. This difficulty arises from the novelty and management complexity of DMDs, not to mention the personal circumstances of patients which need to be taken into consideration in order to eventually reach a shared decision. Aim To explore and understand the holistic decision-making experience of treatment choices and family planning for women living with MS, to facilitate an improvement in the quality of the processes and decisions involved. Objectives 1. To identify the available literature on the effects of switching and managing treatment to allow for pregnancy in women with MS. 2. To explore the real-life experiences of women with MS when choosing, switching, or managing medications, and how they arrange their family plans accordingly. 3. To explore the experiences of key healthcare providers (HCPs) who support these women in such decisions. 4. To identify available resources to help women with these decisions. 7 5. To explore what women needs to see in decision tools to help them with decisions through evaluation of an available online decision aid. Methods The methods were selected to match the objectives: Objective 1 was addressed via a systematic review; Objectives 2, 3, and 4 were reached through qualitative interviews with women with MS and their HCPs (consultants, nurses, and pharmacists); and Objective 5 was attained through qualitative Think Aloud sessions with women with MS. Results The systemic review showed the scarcity of published research focusing on medication decision-making when planning pregnancy, as well as its effect on a woman’s MS. The interview studies showed that despite the importance of this area, it still needs more attention and standardisation of services to create a better care experience. The lack of all kinds of resources (time, information, human) for this for both women and their HCPs is also a challenge. The interviews highlighted the importance of the timing of decisions and patient readiness to decide, which has been found to be regularly compromised by the biographical disruption caused by illness. The Think Aloud sessions collected very useful ideas from its primary users to amend the online MS Trust tool. This serves as an important outcome/output of this thesis. Conclusion This thesis sheds light on medication management as it intersects with family planning decisions, and addresses the need for service standardisation, more patient-friendly information resources, the consideration of patient readiness to make decisions, and27 0Item Restricted Brain Imaging Biomarkers in Multiple Sclerosis(2023-05-10) Altokhis, Amjad; Evangelou , Nikos; Constantinescu, CrisBackground: Iron rim lesions (IRLs), white matter lesions (WMLs) accumulation and linear brain atrophy measurements have been suggested to be important imaging biomarkers in multiple sclerosis (MS). The extent to which these markers are related to MS diagnosis and predict disease prognosis remains unclear. Furthermore, research Magnetic Resonance Imaging (MRI) findings need validation in clinical settings before they can be incorporated into clinical practice. Methods: I conducted two reviews one was a mapping review on IRLs and the other was a meta-analysis on WMLs in MS. I then tested the diagnostic and prognostic usefulness of the IRL in two studies: (1) a large, cross-sectional, multi-centre study of patients with MS and mimicking disorders using 3T MRI, (2) a retrospective single-centre study of patients with first presentation of a clinically isolated syndrome (CIS) or at the early stage of the disease using 7T MRI. I also explored the utility of routine, non-standardised MRI scans measuring WMLs number, volume and linear measures of atrophy at the early stage of the disease and examined their role in predicting long-term disability. Results: The IRLs achieved high specificity (up to 99%) in diagnosing MS compared to MS-mimics but low sensitivity of 24%. All patients with IRLs showing a central vein sign (CVS) had MS or CIS, giving a diagnostic specificity of 100% but equally low sensitivity of 21%. Moreover, the presence of IRLs was also a predictor of long-term disability, especially in patients with ≥4 IRLs. IRLs had a greater impact on disability compared to the WMLs number and volume. Linear brain atrophy of Inter-Caudate Distance (ICD) and Third Ventricle Width (TVW) had a significant impact in predicting disability after 10 years. Conclusions: The perilesional IRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS. Also, the presence and number of IRLs hold prognostic value for long-term physical disability in MS. Simple and reliable assessment of brain atrophy remains challenging in clinical practice.18 0