Characterization of the Molecular Mechanisms Underlying the Chronic Phase of Stroke in a Cynomolgus Monkey Model of Induced Cerebral Ischemia

Stroke
is one of the main causes of mortality and long-term disability
worldwide. The pathophysiological mechanisms underlying this disease
are not well understood, particularly in the chronic phase after the
initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified
infarct volumes as a measure of the stroke severity 28 days after
the ischemic episode, was evaluated using qualitative and quantitative
proteomics analyses. By using multiple online multidimensional liquid
chromatography platforms, 8790 nonredundant proteins were identified
that condensed to 5223 protein groups at 1% global false discovery
rate (FDR). After the application of a conservative criterion (5%
local FDR), 4906 protein groups were identified from the analysis
of cerebral cortex. Of the 2068 quantified proteins, differential
proteomic analyses revealed that 31 and 23 were dysregulated in the
elevated- and low-infarct-volume groups, respectively. Neurogenesis,
synaptogenesis, and inflammation featured prominently as the cellular
processes associated with these dysregulated proteins. Protein interaction
network analysis revealed that the dysregulated proteins for inflammation
and neurogenesis were highly connected, suggesting potential cross-talk
between these processes in modulating the cytoskeletal structure and
dynamics in the chronic phase poststroke. Elucidating the long-term
consequences of brain tissue injuries from a cellular prospective,
as well as the molecular mechanisms that are involved, would provide
a basis for the development of new potentially neurorestorative therapies.