Characterizing rat brain tissue properties during postnatal development and in experimental hydrocephalus using magnetic resonance imaging and light sheet microscopy

The research described in this thesis encompassed three studies related to the biomechanical and vascular factors in acute obstructive hydrocephalus using the rat as a model. In the first study, early postnatal longitudinal brain mechanical properties were monitored in healthy rats and magnetic resonance elastography (MRE) data was found correlating to major cellular integrity changes within the tissue, such as neuronal proliferation and myelination process. In the second study, the effect of internal mechanical impact on the adult rat brains with induced acute obstructive hydrocephalus was investigated using MRE, diffusion tensor imaging and histological stainings. In comparison to the study results and previous work in juvenile animals, lead us to the conclusion that the response of the brain to acute obstruction of the intracranial CSF pathway is dependent on the age of onset. In the third study, hydrocephalic rat brains from the second study were used for further investigations on whether there were any vascular alterations due to the ventricular enlargement and contribute towards the mechanical properties. Samples were treated with CUBIC tissue clearing method and 3D images were obtained by the light sheet microscopy. Qualitative analysis showed that hydrocephalic periventricular arterials and arterioles volume ratio seemed lower than in the control, indicating a loss in arterial and arteriole numbers from the disease. To conclude, the research outlined in this dissertation extended our knowledge of the change in brain tissue properties in normal development and under pathological conditions like hydrocephalus. Brain tissue mechanical properties undergo dynamic changes during postnatal development, in parallel with complex microstructural changes such as neuronal proliferation, synaptic adaptation, and myelination. There are key differences in the brain response to obstructive hydrocephalus induced in young and adult rats. The findings are likely underpinned by differences in brain tissue microstructure and mechanical properties at the time of hydrocephalus induction. While young rats are undergoing critical cerebral development stages, mechanical forces associated with ventricular enlargement may also influence long term brain development, leading to irreversible neural deficits