Heterogeneity in brain distribution of activated microglia and astrocytes in a rat ischemic model of Alzheimer’s disease after 2 years of survival

Abstract

Recent research has shown that the ischemic brain injury could induce the neuropathology of Alzheimer's disease type, possibly facilitating the development of dementia, due to amyloidogenesis-processing of the amyloid protein precursor into amyloid [7-9], as well as to the changes in the structure of the tau protein [10-13]. It has

Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia

“…In the regions of massive neuronal damage, an intense response of microglia and astrocytes was observed [ 18 , 22 , 23 , 67 , 68 , 95 ]. Additionally, postischemic astrocytes in the hippocampal CA1 region showed an enhanced response to cytokines [ 95 ].…”

“…Second, the postischemic brain generates a unique pattern of disappearance of neuronal cells in the CA1 area of the hippocampus with serious general brain atrophy, which is similar to the atrophy noted in Alzheimer’s disease [ 17 , 18 , 19 , 20 , 21 ]. Third, neuroinflammatory reactions have an important role in the progress of the postischemic brain and Alzheimer’s disease [ 22 , 23 ]. Fourth, the data suggest that postischemic brain injury with recirculation can trigger the neuropathology of folding proteins characteristic of Alzheimer’s disease by generation and accumulation of amyloid [ 19 , 24 , 25 , 26 ].…”

Shared Genomic and Proteomic Contribution of Amyloid and Tau Protein Characteristic of Alzheimer’s Disease to Brain Ischemia

“…After cerebral ischemia in humans, the increase in plasma levels of amyloid and tau protein negatively correlated with clinical outcome, which reflected the degree of brain damage [50,[53][54][55][56]. It seems that post-ischemic brain injury promotes the development of irreversible neurodegeneration of the Alzheimer's disease type with massive neuronal loss [1,2], neuroinflammation [20,22,23], changes in white matter with general brain atrophy [1,2,26,27], and accumulation of amyloid [2,43,52] and dysfunctional tau protein [3,61,63,117]. Although significant progress has recently been made in studying the pathogenicity of amyloid and tau protein after ischemia, key mechanisms involved in irreversible ischemic brain neurodegeneration induced by amyloid and tau protein are still unknown.…”

“…Increased level of amyloid and tau protein after brain ischemia in serum [50,[53][54][55][56][126][127][128][129][130][131] and cerebrospinal fluid [131,132] combine the pathology of amyloid and tau protein with ischemic blood-brain barrier failure [133]. In addition, oxidative stress [134] and neuroinflammation [20,22,23] induced by increased permeability of the blood-brain barrier can initiate phosphorylation of tau protein and development of neurofibrillary tangles after ischemia [3,75,[135][136][137][138][139]. Increased plasma tau protein [53,55] may cross the ischemic blood-brain barrier, and blood-derived tau protein may increase brain pathology after ischemia [140].…”

“…Changes in white matter and activation of neuroglial cells in the brain were observed in both humans and animals after ischemia [1,2,[14][15][16][17][18][19][20][21][22][23]. In experimental models of transient brain ischemia, ischemia causes serious alterations in both the corpus callosum and subcortical white matter [2,17,18,24].…”