The Relationship Between Cerebral Reperfusion And Regional Expression Of Matrix Metalloproteinase-9 In Rat Brain Following Focal Cerebral Ischemia. (15th January 2021)

• Record Type: Journal Article
• Authors: Douglas, A.S.; Shearer, J.A.; Okolo, A.; Pandit, A.; Gilvarry, M.; Doyle, K.M.
• Is Part Of: Neuroscience. Volume 453(2021)
• Page Start: 256
• Page End: 265
• Publication Date: 2021-01-15
• Subjects: BBB blood brain barrier -- CBF cerebral blood flow -- IL-1β interleukin-1β -- MMPs matrix metalloproteinases -- PBS phosphate buffered saline -- RT room temperature -- TTC triphenyltetrazolium chloride; MMP-9 -- ischaemic stroke -- MCA occlusion rat model -- reperfusion -- hemispheric lesion volume; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.10.034
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: We investigated the effect of full and partial reperfusion on MMP-9 expression. Partial reperfusion reduced %HLV and oedema but less pronounced than full reperfusion. MMP-9 expression increased in the lesioned anterior and posterior temporal cortex. Both partial and full reperfusion reduced the regional MMP expression significantly. This study shows MMP-9 brain levels reduce relative to the extent of reperfusion. Abstract: We investigated the effect of full and partial mechanical reperfusion on MMP-9 expression in rat brain following middle cerebral artery occlusion, mimicking mechanical thrombectomy. Using percentage hemispheric lesion volume and oedema as measures, partial reperfusion reduced extent of brain damage caused by MCA occlusion, but the protective effect was less pronounced than with complete reperfusion. Using ELISA quantification in fresh frozen tissue, confirmed by immunofluorescence in perfusion fixed tissue, increased MMP-9 expression was observed in infarcted tissue. MMP-9 was increased in lesioned tissue of the anterior and posterior temporal cortex and underlying striatal tissue, but also the normal appearing frontal cortex. No significant increase in MMP-9 in the hippocampus was observed, nor in the unlesioned contralateral hemisphere. Both partial reperfusion and full reperfusion reduced the regional MMP expression significantly. The highest levels of MMP-9 were observed in lesioned brain regions in the non-reperfused group. MMP-9 expression was evident in microvessels and in neuronal cell bodies of affected tissue. This study shows that MMP-9 brain levels are reduced relative to the extent of reperfusion. These observations suggest targeting early increases in MMP-9 expression as a possible neuroprotective therapeutic strategy and highlight the rat MCA occlusion model as an ideal model in which to study candidate therapeutics.