Pereira-Jennings, Stella; (2000) Are treatment strategies designed for acute cerebral ischaemic strokes hazardous or beneficial in cerebral haemorrhage? Experimental findings from an animal model of intracerebral haemorrhage: Reproducibility of the model and assesment of treatment strategies. Masters thesis (M.Phil), UCL (University College London).

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Abstract

Haemorrhagic stroke, although of less frequent occurrence, has the highest mortality rate. In the emergency situation where a patient is suspected of having a stroke, immediate therapeutic strategies have been proposed to stabilise the clinical status and prevent further deterioration. However, these regimes are modelled on ischaemic strokes. The plan of the project was to determine the possible outcomes of some of these treatments; osmotherapy, inhibition of cyclo-oxygenase, antagonism of the glutamate receptor, induced hypertension, anticoagulation and thrombolysis, when applied to an experimental model of intracerebral haemorrhage. Rosenberg's et al (1990) rat model of collagenase-induced haemorrhage was chosen due its similarity to the clinical situation. The suitability of Rosenberg's et al (1990) haemorrhagic model was first evaluated. This involved measurements of the haematoma volume, its consequent effect on brain swelling, evidence of a dysfunctional blood brain barrier and any associated ischaemic change. Attention was given to the reliability and reproducibility of these measures. Results indicate that the cause of cerebral swelling associated with intracerebral haemorrhage is complex. Treatment with either glycerol, dexamethasone or indomethacin were found to be effective in reducing water accumulation, suggesting a role for both cytotoxic and vasogenic oedema respectively. The haematoma volume was predictably increased significantly by heparin. Clinical outcome was also worse with heparin. Unexpectedly, larger haematomas and worse outcome occurred with the administration of 10mg kg⁻¹ indomethacin and 5mg kg⁻¹ MK-801. The possible existence of ischaemic brain damage due to haematoma formation was also addressed in this project. Although no histological proof was evident, there were indirect signs of its likely presence. This was reflected in the improvement of the animals' recovery status seen with induced hypertension, 1 mg kg⁻¹ MK-801, and possibly but unexpectedly with tissue plasminogen activator. It is argued that the collagenase model presents a potentially valuable means of assessing whether new therapies for ischaemic stroke, being investigated in models of cerebral ischaemia, have the potential to improve the outcome of cerebral haemorrhage or cause deterioration.

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