Assessing the effects of cytoprotectants on selective neuronal loss, sensorimotor deficit and microglial activation after temporary middle cerebral occlusion

Julius V. Emmrich, Sohail Ejaz, David J. Williamson, Young T. Hong, Sergey Sitnikov, Tim D. Fryer, Franklin I. Aigbirhio, Heike Wulff, Jean Claude Baron

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 [11 C]-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.

Original languageEnglish (US)
Article number287
JournalBrain Sciences
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

Keywords

  • Ischemic stroke
  • KCa3.1
  • Microglial activation
  • PET
  • Reperfusion injury
  • Selective neuronal loss
  • TRAM-34

ASJC Scopus subject areas

  • Neuroscience(all)

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