Apoptotic markers and DNA damage are related to late phase of stroke: Involvement of dyslipidemia and inflammation

Prospective clinical biomarkers of caspase-mediated apoptosis associated with neuronal and neurovascular damage following stroke and other severe brain injuries: Implications for chronic neurodegeneration

“…Notably, similar pathways are involved in neurodegenerative disease. [ 111 117 ] Involvement of extrinsic apoptotic mechanisms is also suggested from clinical studies showing correlations of caspase-3 and/or caspase-8 activation with upregulation of death receptors (e.g., Fas) and death receptors ligands (e.g., TNF-α) in stroke[ 74 86 87 88 ] and TBI[ 77 151 ] patients. Similar findings were reported in preclinical models of stroke[ 143 163 164 165 ] and TBI.…”

“…Expression of Fas and/or Fas ligand has been reported in stroke[ 74 75 ] and severe TBI patients[ 76 77 78 ] and documented in preclinical models of brain ischemia[ 79 80 81 ] and TBI. [ 82 83 84 85 ] Upregulation of TNF-α has been reported in clinical stroke studies including ischemic[ 86 87 88 ] and animal TBI models. [ 83 84 85 89 90 ] TNF-α might contribute to neuronal injury as well as exert protective effects.…”

“…Activation of caspase-3 through caspase-8-mediated pathways in TBI[ 78 151 ] and stroke[ 86 88 162 ] pathology suggests involvement of extrinsic apoptotic mechanisms in these disorders. Notably, similar pathways are involved in neurodegenerative disease.…”

“…Numerous clinical studies have demonstrated upregulation of caspase-3 following ischemic and hemorrhagic strokes and TBI in postmortem and surgically removed brain tissues,[ 74 77 95 157 158 159 162 171 172 180 195 ] CSF,[ 77 197 ] and blood plasma. [ 86 87 88 181 182 183 ] Other major caspases that are upregulated following activation after injuries include caspase-1,[ 158 191 ] caspase-7,[ 86 148 ] and caspase-8. [ 75 78 88 ] Immunohistochemical studies revealed that caspase-1 upregulation was observed in the brain tissue, blood vessels, T-lymphocytes, and CD68positive macrophages; these caspase-1 increases were associated with Bcl-2, interleukin 1 β, and NLRP3 levels.…”

“…[ 86 87 88 181 182 183 ] Other major caspases that are upregulated following activation after injuries include caspase-1,[ 158 191 ] caspase-7,[ 86 148 ] and caspase-8. [ 75 78 88 ] Immunohistochemical studies revealed that caspase-1 upregulation was observed in the brain tissue, blood vessels, T-lymphocytes, and CD68positive macrophages; these caspase-1 increases were associated with Bcl-2, interleukin 1 β, and NLRP3 levels. [ 158 191 ] Caspase-3 upregulation was observed in neurons[ 157 180 ] and in CD68-positive cells, including infiltrating macrophages and microglia.…”