Browsing by Author "Rissanen, Anna"
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Item Cell-based therapies and functional outcome in experimental stroke(2009) Rissanen, Anna; Schallert, Timothy; Jolkkonen, JukkaOne of the most promising frontiers in neuroscience is the potential for stem cells to treat brain damage. Cell-based strategies are of particular interest in neurological conditions because mature brains have limited capacity for self-repair. It is often argued that stem cells might be used to replace lost neurons and restore function (Lindvall et al., 2004). Prior to clinical trials, safety and efficacy must be demonstrated in animal models. Indeed, a recent review strongly suggests that preclinical and clinical trial procedures and outcome measures, including behavioral assessments, must be closely aligned and sophisticated (Ginsberg, 2008). Unfortunately, a lack of translational success has been observed in stroke neuroprotection trials conducted thus far, and this experience should serve to caution that histological benefits in animals are not a sufficient reason to move to the clinic carelessly.Item Challenges and possibilities of intravascular cell therapy in stroke(2009) Rissanen, Anna; Jolkkonen, JukkaStroke is the third leading cause of death in Western countries and more importantly a leading cause of adult disability. The recovery process of stroke patients might be enhanced by intensive rehabilitation, which acts through brain plasticity mechanisms. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help patients even when treatment is initiated days or weeks after the ischemic insult. An extensive number of experimental transplantation studies have been conducted with cells of different origins (e.g., embryonic stem, fetal neural stem, human umbilical cord blood) with promising results. Noninvasive intravascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. However, surprisingly little is known about whole body biodistribution of intravascularly administered cells and mechanisms leading to improved functional recovery. This review examines the recent literature concerning intravascular cell-based therapies in experimental stroke.Item Effectiveness of virtual discovery learning in medicine(2024) Rissanen, Anna; Bistritz, Lana M.; Petrov, Petar A.Background/Purpose - After pandemic restrictions were lifted, students were interested in retaining hybrid learning options. In response, the MD program offered a Virtual Discovery Learning (DL) stream during pre-clerkship. This study compares the learning outcomes of virtual vs in-person DL students in the Gastroenterology and Nutrition course. Methods - Using mixed methods, students were separated into Virtual and In-person DL groups. Learning outcome data was collected and anonymized. Overall student performance for MCQ assessments and performance for DL specific questions in those assessments was compared between the two groups using two-tailed T-Test with two sample unequal variance. Qualitatively, we performed focus groups where students provided feedback on their Virtual DL experience, their reasoning for choosing the Virtual DL stream and their impressions of the experience. Results - Statistical analysis of student performance data concluded that there were no statistically significant differences in grade averages between the Virtual and In-person DL groups for the GI final exam (p=0.92), except for one DL specific question on the final (p=0.008). Focus group sessions identified 4 main themes for why students chose virtual learning: Covid-19; Flexibility; Accessibility and Learning Preferences; and Mental Health. Discussion - Students who chose to attend Discovery Learning virtually did not experience any academic advantage or disadvantage in learning compared to students who attended DL in-person, and psychosocial benefits of virtual attendance were identified. This suggests that an optional hybrid model for DL is potentially beneficial to students without impacting learning outcomes.Item Effects of ovariectomy and estrogen treatment on learning and hippocampal neurotransmitters in mice(2002) Heikkinen, Taneli; Puoliväli, Jukka; Liu, Li; Rissanen, Anna; Tanila, HeikkiThis study examined the effects of long-term estrogen treatment (sc 17β-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7- and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice.Item Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke(2007) Rissanen, Anna; Hewlett, K.; Windle, V.; Chernenko, Garry A.; Ploughman, M.; Jolkkonen, Jukka; Weiss, S.; Corbett, DaleStroke patients suffer from severe impairments and significant effort is under way to develop therapies to improve functional recovery. Stem cells provide a promising form of therapy to replace neuronal circuits lost to injury. Indeed, previous studies have shown that a variety of stem cell types can provide some functional recovery in animal models of stroke. However, it is unlikely that replacement therapy alone will be sufficient to maximize recovery. The aim of the present study was to determine if rodent stem cell transplants combined with rehabilitation resulted in enhanced functional recovery after focal ischemia in rats. Middle cerebral artery occlusion was induced by injection of the vasoconstrictive peptide endothelin-1 adjacent to the middle cerebral artery. Seven days after stroke the rats received adult neural stem cell transplants isolated from mouse subventricular zone or vehicle injection and then subsequently were housed in enriched or standard conditions. The rats in the enriched housing also had access to running wheels once a week. Enriched housing and voluntary running exercise enhanced migration of transplanted stem cells toward the region of injury after stroke and there was a trend toward increased survival of stem cells. Enrichment also increased the number of endogenous progenitor cells in the subventricular zone of transplanted animals. Finally, functional recovery measured in the cylinder test was facilitated only when the stem cell transplants were combined with enrichment and running exercise 7 days after the transplant. These results suggest that the ability of transplanted stem cells in promoting recovery can be augmented by environmental factors such as rehabilitation.Item Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation(2004) Heikkinen, T.; Kalesnykas, G.; Rissanen, Anna; Tapiola, T.; Iivonen, S.; Wang, J.; Chaudhuri, J.; Tanila, H.; Miettinen, R.; Puoliväli, JukkaWe investigated the effects of ovariectomy (OVX) and 17β-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (Aβ) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the Aβ-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to Aβ-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of Aβ or formation of amyloid plaques.Item In mice tonic estrogen replacement therapy improves non-spatial and spatial memory in a water maze task(1999) Rissanen, Anna; Puoliväli, Jukka; van Groen, Thomas; Riekkinen, Paavo Jr.Investigated the effects of estrogen replacement therapy on water maze non-spatial and spatial navigation in mice. Three groups of mice were ovariectomized and two of these groups being implanted with s.c. pellets that produce blood levels of estrogen close to those found in estrous (estrogen low, 75–100 pg/ml blood) or proestrous (estrogen high, 300–400 pg/ml). The behavioral assessment was initiated 7 days after pellet implantation. Non-spatial navigation to a clearly visible platform was stimulated by low and high levels of estrogen. However, spatial navigation to a hidden platform was improved by low estrogen levels. We found that estrogen improves two different types of memory processes that depend on striatal (non-spatial navigation) and hippocampal (spatial) memory systems.Item Interdisciplinary supports for student mental health: Pets Assisting With Student Success - PAWSS at MacEwan University(2024) Bialowas, Payden; Oloriz, Abby; Rissanen, AnnaStudent mental health is a critical concern in academic environments, where the pressures of academic life can significantly impact well-being. This study investigates the effectiveness of animal-assisted therapy in alleviating mental health challenges. Collaborating with the Pet Assisting With Student Success (PAWSS) program at MacEwan University, we aimed to understand how interactions with therapy animals could benefit students. Employing a qualitative phenomenological approach, we gathered data on student experiences with the PAWSS program through Qualtrics. Through the survey, we explored the way in which the program influenced students' daily lives and their ease of accessing these therapeutic interactions and considered improvements that could be made to make the program more accessible to students. Participants consistently reported reductions in anxiety and stress after engaging with the PAWSS events or encountering therapy animals in hallways. Our poster includes common themes about students’ experiences with the PAWSS program, which are visually reflective through NVivo. Our findings highlight the profound positive impact of animal-assisted therapy on student stress levels and overall mental health. The human-animal bond fostered through the PAWSS program not only provides immediate relief but also cultivates a supportive campus environment. This research underscores the value of interdisciplinary approaches to mental health support and the transformative potential of integrating animal-assisted therapy into university settings.Item Long-term assessment of enriched housing and subventricular zone derived cell transplantation after focal ischemia in rats(2008) Rissanen, Anna; MacLellan, Crystal L.; Chernenko, Garry A.; Corbett, DaleThe potential for using stem cells to treat stroke has garnered much interest, but stem cell therapies must be rigorously tested in animal models before transplantation studies progress to clinical trials. An enriched environment enhances transplanted subventricular zone (SVZ) cell migration and functional benefit following stroke in rats. However, the ability of SVZ cells to survive, migrate, differentiate and promote functional recovery at protracted survival times (e.g., 3 months) has not been investigated. The vasoconstrictive peptide endothelin-1 was injected adjacent to the middle cerebral artery to produce focal ischemia. Seven days later, cells derived from the SVZ of adult mice (800,000 cells/rat or vehicle injection) were transplanted into the sensory-motor cortex and striatum, and rats were then housed in enriched or standard conditions. Rats in enriched housing had access to running wheels once per week. Recovery was assessed in the forelimb-use asymmetry task (cylinder) at 1, 2, or 3 months after transplantation immediately prior to euthanasia. Transplanted cell survival and migration were quantified using stereology. Cell phenotype was determined with immunohistochemistry and confocal microscopy. Enriched housing did not enhance survival or migration of transplanted SVZ cells at protracted survival times, and the majority (~ 99%) of cells died within 2 months of transplantation. Cell survival was significantly, and negatively, correlated with microglial activation. Many surviving cells expressed an astrocytic phenotype. Functional recovery was not improved at any time. Therapies involving transplantation of SVZ cells following stroke must be further optimized in order to enhance long-term cell survival and thereby maximize functional benefit.Item Mental health supports for post-secondary students - focus on animal-assisted wellness and trauma-informed practices(2024) Rissanen, AnnaMental health-related problems, stress and symptoms of mental illness have been increasing in Canadian postsecondary students. We need more focus on interdisciplinary campus services that help struggling students such as animal-assisted therapy on campus. Also, an important area of interest is understanding the psychosocial determinants of mental health such as the effects of adverse childhood experiences (ACEs), experienced trauma, and added distress from discrimination and racism on post-secondary students. It is important for professors, administrators, and others to understand trauma-informed practices to prevent further harm. In attempts to avoid poor academic performance, and further accumulation of psychosocial problems, we need to address the needs of students. Specifically, trauma informed practices need exploration as research on trauma informed teaching and clinical practice are underutilized in Canadian campuses. Also, it is important to explore interdisciplinary therapy services, such as animal-assisted therapy that has a low barrier of participation. The overall goal for university administrators is to understand the complexity of student mental health that encompasses the diversity of post-secondary students’ mental health challenges, including interdisciplinary and trauma-informed practices. In this presentation I will present the results of a survey about trauma-informed practices utilized in Canadian universities. Also, I will share the results of a preliminary study about the effectiveness of animal-assisted therapy on a Canadian University campus. There is potential that this preliminary research will lead to further studies on how to educate campus members in trauma-informed practices, and further understanding of how we can prevent worsening of traumatized students' distress and improve their quality of life. Also, these are novel research results about additional treatments in student mental health, specifically on animal-assisted wellness and trauma-informed practices in post-secondary education.Item Prolonged bihemispheric alterations in unfolded protein response related gene expression after experimental stroke(2006) Rissanen, Anna; Sivenius, Juhani; Jolkkonen, JukkaAfter ischemia, endoplasmic reticulum (ER) stress pathways are activated that include unfolded protein response (UPR) and protein synthesis inhibition (PSI). Both of these mechanisms aim to restore ER functioning mainly by inhibition of translation and increased processing of excess proteins in ER. We were interested in the role of these pathways during spontaneous recovery after transient middle cerebral artery occlusion (MCAO) in rats. The spontaneous recovery of rats was assessed with a limb-placing test. The expression of ER-stress-related genes (IRE1, ATF6, GRP78, eif2α, ATF4, PERK) was studied by using in situ hybridization in different brain areas on post-operative days 2, 7, 14 and 28. Elevated signals were detected in striatum contralateral to the lesion on days 2 (PERK and IRE1) and 14 post-ischemia (IRE1). Gene expression was elevated on day 7 in the striatum ipsilateral to the lesion (ATF6 and GRP78) and on day 14 (GRP78) post-ischemia. Furthermore, elevated levels of GRP78 were detected on day 14 after ischemia in the ipsilateral sensorimotor cortex. These results suggest that altered gene expression related to unfolded protein response may be more long lasting than expected following focal cerebral ischemia. In addition, these results show that the response to ER stress differs ipsi- and contralaterally after MCAO in rats. Since these differences are detected in both hemispheres only in areas adjacent to the lesion, UPR may contribute to spontaneous recovery after MCAO in rats.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, JukkaCortical 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.