Assessing the Effects of Cytoprotectants on Selective Neuronal Loss, Sensorimotor Deficit and Microglial Activation after Temporary Middle Cerebral Occlusion.
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Authors
Emmrich, Julius V
Ejaz, Sohail
Williamson, David
Hong, Young
Sitnikov, Sergey
Fryer, Timothy
Wulff, Heike
Publication Date
2019-10-22Journal Title
Brain Sci
ISSN
2076-3425
Publisher
MDPI AG
Volume
9
Issue
10
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Emmrich, J. V., Ejaz, S., Williamson, D., Hong, Y., Sitnikov, S., Fryer, T., Aigbirhio, F., et al. (2019). Assessing the Effects of Cytoprotectants on Selective Neuronal Loss, Sensorimotor Deficit and Microglial Activation after Temporary Middle Cerebral Occlusion.. Brain Sci, 9 (10) https://doi.org/10.3390/brainsci9100287
Abstract
Although early reperfusion after stroke salvages the still-viable ischemic tissue, peri-infarct selective neuronal loss (SNL) can cause sensorimotor deficits (SMD). We designed a longitudinal protocol to assess the effects of cytoprotectants on SMD, microglial activation (MA) and SNL, and specifically tested whether the KCa3.1-blocker TRAM-34 would prevent SNL. Spontaneously hypertensive rats underwent 15 min middle-cerebral artery occlusion and were randomized into control or treatment group, which received TRAM-34 intraperitoneally for 4 weeks starting 12 h after reperfusion. SMD was assessed longitudinally using the sticky-label test. MA was quantified at day 14 using in vivo [11C]-PK111195 positron emission tomography (PET), and again across the same regions-of-interest template by immunofluorescence together with SNL at day 28. SMD recovered significantly faster in the treated group (p = 0.004). On PET, MA was present in 5/6 rats in each group, with no significant between-group difference. On immunofluorescence, both SNL and MA were present in 5/6 control rats and 4/6 TRAM-34 rats, with a non-significantly lower degree of MA but a significantly (p = 0.009) lower degree of SNL in the treated group. These findings document the utility of our longitudinal protocol and suggest that TRAM-34 reduces SNL and hastens behavioural recovery without marked MA blocking at the assessed time-points.
Identifiers
External DOI: https://doi.org/10.3390/brainsci9100287
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300674
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