Salihu, Abubakar Tijjani
(2016)
Evaluation of motor deficits and perihaematomal neuronal degeneration in a mouse model of cerebellar haemorrhage.
Masters thesis, Universiti Sains Malaysia.
Abstract
Improved clinical imaging and early surgery, when indicated, have been shown
to decrease mortality rate after cerebellar haemorrhage. Nonetheless, the long term
functional outcome in the majority of the survivors is still very alarming; irrespective of
whether they receive surgical or conservative management. Evidently, the development
of definitive medical treatment to use alone or in combination with surgery in order to
improve outcome in this condition is hampered by lack of proper understanding of the
disease pathophysiology. Following cerebellar haemorrhage, brain tissue inside the
hematoma can be considered equivalent to the ischemic core in ischaemic stroke, and is
unlikely to be salvageable. However, delayed neuronal loss due to various secondary
injury mechanisms might continue in the vicinity of the haemorrhage and this could
contribute to the persistent disability in the patients. The aim of this study is to evaluate
the histomorphological changes of the perihaemorrhagic tissue after experimental
cerebellar haemorrhagen in mice. We hypothesized that delayed neuronal degeneration
occurs in the perihaematomal area after intracerebellar haemorrhage. Adult male Swiss
albino mice were stereotactically infused with collagenase type VII (0.4U in 1ml saline)
unilaterally in to the cerebellum, following anaesthesia. The animals in the sham group
were injected with normal saline, while the control animals were not injected with
anything. Motor deficits were assessed using open field and composite score for
evaluating mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase
infusion and the animals were sacrificed at the same time interval for evaluation of
perihaematomal neuronal degeneration using haematoxylin and eosin staining and
Annexin V-FITC/ Propidium iodide assay. At the end of the study, it was found that
infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the
mice especially within the first week post surgery and this gradually improved within
three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear
pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7
days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in
the perihaematomal area were phagocytosed and the remaining neuronal cells around
the scar tissue appear normal. Moreover, Annexin-V/propidium iodide–positive cells
were observed at the perihaematomal area at 3 and 7 days implying that the neurons
likely die via apoptosis. It was concluded that a population of potentially salvageable
neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a
wide time window that could be amenable to treatment.
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