The effect of mechanical reperfusion outcome following an occlusive stroke on the regional expression of matrix metalloproteinase-9 in rat brain

Background and Aims This study investigated the effect of different mechanical reperfusion outcomes following occlusive stroke on a marker of blood brain barrier dysfunction matrix metalloproteinase-9 (MMP-9). Method Male Sprague Dawley rats underwent 2 hour middle cerebral artery occlusion (MCAO) (n=6-14 per group). Following occlusion, different reperfusion strategies were employed for a further 2 hours; either full, partial or no reperfusion, simulating cerebral blood flow (CBF) restoration that may occur during thrombectomy. In sham-operated animals, filament insertion was omitted. Results Physiological parameters, including temperature, haemodynamics, blood glucose and gases were within normal parameters with no difference between groups throughout. MCAO caused a drop in CBF to 50% of pre-occlusion level (F(3,37)=10.57; p0.001). Reperfusion approach had a significant effect on CBF (F(2,27)=5.12; p0.05); 78%, 53% and 43% of sham levels for full, partial and no reperfusion groups respectively. Occlusion resulted in significant infarction (F(3,26)=3.03; p0.05), most prominent in non-reperfused animals, and also significant oedema (F(3,26)=5.49; p0.01). Occlusion resulted in increased MMP-9 expression in the lesioned hemisphere in the frontal cortex (F(1,52)=15.51; p0.001), striatum (F(1,52)=39.98; p0.001), anterior temporal cortex (F(1,52)=63.85; p0.001) and posterior temporal cortex (F(1,52)=13.34; p0.001), but not the hippocampus (F(1,52)=2.00; ns). MMP-9 expression was higher in animals not reperfused than those fully or partially reperfused, particularly in the striatum (F(3,52)=11.53; p0.001) and anterior temporal cortex (F(3,52)=10.35; p0.001). Conclusion Permanent occlusion resulted in greater infarct, oedema and MMP-9 expression than full or partial reperfusion, supporting the clinical benefits of early thrombectomy indicating the benefit of even partial reperfusion.