Mapping post-stroke brain activation patterns: How do they change over time?
Basnayake, Nuvindi
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Basnayake, N. (2018). Mapping post-stroke brain activation patterns: How do they change over time? (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/8586
Permanent link to OUR Archive version:
http://hdl.handle.net/10523/8586
Abstract:
Stroke is a leading cause of death and long-term disability worldwide. Despite decades of research on neuroprotection, only few therapies are currently available to minimise the extent of infarction. As a result, researchers are now investigating the recovery process of the brain after a stroke. To this point, many studies have noted changes to neuronal connections after a stroke and some have noted that this organization can potentially aid the functional recovery after stroke. However, a pattern in the activation of neurons after stroke should first be established to evaluate how the neuronal connections change after stroke. Therefore, the present study aimed to establish maps of neuronal activation patterns within discreet brain regions in response to a spatial memory task, after inducing a prefrontal cortex (PFC) stroke. As a secondary aim, variations in neuronal activation patterns at two separate time points were analysed to determine if neuronal connections are either gained or lost over time after stroke. For this secondary aim, it was hypothesised that the neuronal connections would be lost. This hypothesis was based on the previously observed delayed impairments in spatial memory following strokes to Prefrontal Cortex (PFC).Tetracycline transactivator controlled genetic tagging (TetTag) mice with CD-1 background were used in the present study. A photothrombotic focal stroke was induced to the prefrontal cortex (PFC) of the mice and their spatial memory impairments were assessed using a simple object location recognition test at one-week and four-weeks post-stroke. To tag the active neurons during week one behaviour task, endogenous Green Fluorescent Protein (GFP) was used and this was controlled with a Doxycycline diet to prevent any tagging outside the behaviour testing time window. To tag active neurons during week four testing, exogenous Zinc Finger Protein (ZIF) was used. After week four testing, mice were transcardially perfused and histologically assessed to determine the infarction volume and the extent of the subsequent glial scar. Confocal microscope was also used to analyse the GFP-tagged and ZIF-tagged neurons which indicate activation at week one and week four, respectively.The quantification of the infarction indicated a lesion with a volume of 0.73 0.48 mm3, that also extended to Premotor cortex (M1). The analysis of reactive astrocytes indicated glial scar which extended beyond white matter tracts. The behaviour analysis indicated that stroke mice in fact had spatial memory impairments compared to sham mice, but the onset of the impairment was not delayed. The corresponding activation of neurons at week one and week four testing also indicated no progressive loss in neuronal connections. Instead, the inactive CA2 and CA3 regions of the hippocampus during week one were active during week four, hence indicating a progressive gain in neuronal connections. To conclude, the present study found no evidence for a progressive loss in neuronal connections post-stroke but the observed spatial memory impairment was not delayed. Therefore, future mapping studies should use the same mouse model that previously demonstrated delayed spatial memory impairments, to determine if neuronal connections are indeed lost in a progressive manner after stroke.
Date:
2018
Advisor:
Clarkson, Andrew
Degree Name:
Bachelor of Biomedical Sciences with Honours
Degree Discipline:
Anatomy
Publisher:
University of Otago
Keywords:
Stroke; Brain Activation; Spatial Memory Impairments; TetTag System; Brain Mapping; Post-stroke Brain Recovery; Post-stroke Cognitive Impairments; Brain; Neuronal Activation; PFC Stroke; Photothrombosis
Research Type:
Thesis
Languages:
English
Collections
- Anatomy [221]
- Thesis - Honours [340]