The relationship between cerebral reperfusion after an occlusive stroke and the development of haemorrhagic transformation in otherwise healthy rats

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB278

Poster Communications: The relationship between cerebral reperfusion after an occlusive stroke and the development of haemorrhagic transformation in otherwise healthy rats

J. A. Shearer1, A. S. Douglas1, B. P. Kirby2, A. Pandit3, K. M. Doyle1

1. Physiology, National University of Ireland, Galway, Ireland. 2. Royal College of Surgeons, Dublin, Ireland. 3. CURAM, National University of Ireland, Galway, Ireland.

View other abstracts by:


15 million people suffer stroke each year according to the WHO. Over 80% of strokes are caused by occlusion. Removal of the occlusion, and subsequent reperfusion can potentially minimise the degree of brain damage. However, post-occlusion, abnormal permeability of the blood brain barrier can lead to haemorrhagic transformation (HT), a potentially fatal complication that can develop with reperfusion. The pathophysiology of HT is not well understood, and it is currently impossible to predict with certainty the likelihood of its occurrence. The aim of this study was to investigate the relationship between cerebral reperfusion after an occlusive stroke and the development of HT using the rat middle cerebral artery (MCA) occlusion model. Increased expression of matrix metalloprotease-9 (MMP-9) in brain tissue is a useful marker of HT. Male Sprague Dawley rats (~ 300g, n=12) underwent 2h occlusion of the MCA, and 2h reperfusion. Sham animals (n=3) had the same surgery, except the occluder was not inserted. Cerebral blood flow (CBF) in the region served by the MCA was measured using laser doppler flowmetry. Rats were killed immediately following the reperfusion period. % hemispheric lesion volume (%HLV) was assessed in TTC stained brain slices. Using ELISA, Western blot and immunohistochemistry, expression of MMP-9 was assessed in the frontal cortex, anterior temporal cortex, posterior temporal cortex, striatum and hippocampus. Factors that influence HT – blood pressure, gases, glucose and temperature were stable and within normal physiological limits throughout. CBF was reduced by 50% in the ipsilateral hemisphere upon occlusion using a monofilament. During the reperfusion period, there was variability in recovery of CBF following removal of the occluder. In some, CBF reached considerably higher levels than pre-occlusion (140% of baseline, n=5), in some CBF recovered to 70% of pre-occlusion level (n=4), and in others CBF did not recover from occlusion levels, despite removal of the monofilament (n=3). Mean %HLV across all groups was 11%. 1-way ANOVA showed no significant difference in %HLV between reperfusion groups. MMP-9 expression was increased in the lesioned anterior temporal cortex vs the contralateral hemisphere and sham animals (2.4 fold higher, (F(3,26)=6.07, p<0.01)). MMP-9 levels were higher in the group with no recovery of CBF during reperfusion in comparison to all other reperfusion groups and sham animals (F(3,11)=7.15, p<0.01). These findings suggest a strong relationship between recovery in CBF and HT in otherwise healthy animals. Further study in this area will enhance understanding of the pathophysiology of HT, which ultimately may lead to a therapeutic approach to minimise its occurrence.



Where applicable, experiments conform with Society ethical requirements.

Site search

Filter

Content Type