Relationship between Neuronal Damage/Death and Astrogliosis in the Cerebral Motor Cortex of Gerbil Models of Mild and Severe Ischemia and Reperfusion Injury

Abstract

Neuronal loss (death) occurs selectively in vulnerable brain regions after ischemic insults. Astrogliosis is accompanied by neuronal death. It can change the molecular expression and morphology of astrocytes following ischemic insults. However, little is known about cerebral ischemia and reperfusion injury that can variously lead to damage of astrocytes according to the degree of ischemic injury, which is related to neuronal damage/death. Thus, the purpose of this study was to examine the relationship between damage to cortical neurons and astrocytes using gerbil models of mild and severe transient forebrain ischemia induced by blocking the blood supply to the forebrain for five or 15 min. Significant ischemia tFI-induced neuronal death occurred in the deep layers (layers V and VI) of the motor cortex: neuronal death occurred earlier and more severely in gerbils with severe ischemia than in gerbils with mild ischemia. Distinct astrogliosis was detected in layers V and VI. It gradually increased with time after both ischemiae. The astrogliosis was significantly higher in severe ischemia than in mild ischemia. The ischemia-induced increase of glial fibrillary acidic protein (GFAP; a maker of astrocyte) expression in severe ischemia was significantly higher than that in mild ischemia. However, GFAP-immunoreactive astrocytes were apparently damaged two days after both ischemiae. At five days after ischemiae, astrocyte endfeet around capillary endothelial cells were severely ruptured. They were more severely ruptured by severe ischemia than by mild ischemia. However, the number of astrocytes stained with S100 was significantly higher in severe ischemia than in mild ischemia. These results indicate that the degree of astrogliosis, including the disruption (loss) of astrocyte endfeet following ischemia and reperfusion in the forebrain, might depend on the severity of ischemia and that the degree of ischemia-induced neuronal damage may be associated with the degree of astrogliosis.

Brain Factor-7® Improves Cognitive Impairment Following Transient Ischemia and Reperfusion Injury in Gerbil Forebrain through Promoting Remyelination and Restoring Cholinergic and Glutamatergic Neurotransmission in the Hippocampus

“…Researchers have established a gerbil model of tFI/R in order to investigate the mechanisms of tFI/R-induced neuronal death and search its neuroprotective and/or therapeutic materials because the model has simple surgical procedure and high reproducibility [22,23,28,29]. In the model, selective neuronal loss is triggered in the CA1 field of the hippocampus at four to five days after tFI/R, and the death is termed as "delayed neuronal death" [9,30].…”

“…The brain tissue sections were prepared according to our previously described method [22]. Shortly, the gerbils were deeply anesthetized with pentobarbital sodium (intraperitoneal injection, 150 mg/kg; JW pharm.…”

Acetylated Tau Protein: A New Piece in the Puzzle between Brain Ischemia and Alzheimer’s Disease

“…Seventh, after cerebral ischemia, dominant neuronal death in the hippocampus is observed, with the development of a general brain atrophy identical to Alzheimer’s disease [ 1 , 18 , 19 , 20 ]. Eighth, the neuroinflammatory response plays an important role in the progression of post-ischemic neurodegeneration, such as in Alzheimer’s disease [ 21 , 22 , 23 ]. Ninth, data show that in post-ischemic brain, Alzheimer’s disease-specific folding proteins such as amyloid and tau protein are induced, leading to the induction of amyloid plaques and neurofibrillary tangles [ 1 ].…”

“…Post-ischemic accumulation of amyloid in the brain associated with increased permeability of the blood–brain barrier [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ] enables the onset of tau protein dysfunction, which supports the link between amyloid accumulation and tau protein modification at some stage of damage to the blood–brain barrier [ 64 ]. Moreover, both oxidative stress [ 72 ] and neuroinflammation [ 21 , 22 , 23 ] cause damage to the blood–brain barrier that may cause hyperphosphorylation of the tau protein and the development of neurofibrillary tangles post-ischemia ( Figure 1 ) [ 51 , 53 , 54 , 73 ]. Moreover, post-ischemia, the plasma-derived tau protein [ 55 , 56 ] crosses the post-ischemic blood–brain barrier in two directions and may exacerbate its own pathology in the brain tissue [ 74 ].…”

“…In addition to the tau protein, there are other mechanisms underlying the association of cerebral ischemia with Alzheimer’s disease, including amyloidosis [ 47 ], neuroinflammation [ 21 , 22 , 23 ] and cerebral amyloid angiopathy [ 24 ]. Increased levels of serum amyloid and tau protein as well as acetylated tau protein indicate that the blood–brain barrier shows increased permeability, as in Alzheimer’s disease [ 64 ].…”