DNA Fragmentation and HSP70 Protein Induction in Hippocampus and Cortex Occurs in Separate Neurons following Permanent Middle Cerebral Artery Occlusions

Abstract

DNA nick end-labeling (TUNEL) and heat shock protein (HSP)70 immunocytochemistry were performed on the same brain sections 1 (n = 6), 3 (n = 12), and 7 (n = 7) days following permanent middle cerebral artery (MCA) occlusions produced in adult rats using the endovascular carotid suture method. In the cortex at 1 and 3 days following MCA occlusions, HSP70 immunoreactive neurons were located outside areas of infarction and showed little evidence of DNA fragmentation. HSP70-stained cortical neurons were intermingled with TUNEL cells near the infarct, but extended for greater distances away from the infarct. DNA fragmentation occurred in CA1 hippocampal neurons in 39% of the animals at 1 and 3 days following ipsilateral MCA occlusion. Bilateral DNA fragmentation occurred in CA1 neurons in one subject. HSP70 protein was expressed in CA1 hippocampal neurons in nine of 18 (50%) animals at 1 and 3 days following MCA occlusions, including all animals that exhibited hippocampal DNA fragmentation. Three animals had bilateral expression of HSP70 in CA1 neurons. Cells that stained for either HSP70 protein or DNA fragmentation existed in close proximity to one another. Approximately 5-7% of HSP70-stained cells were TUNEL stained and 3% of TUNEL-positive cells also stained for HSP70. There was no HSP70 staining or DNA fragmentation in the brains of sham-operated controls (n = 4) or in the brains of animals 7 days following MCA occlusions. These data suggest that ischemic cells capable of translating HSP70 protein generally do not undergo DNA fragmentation. These data support the concept that most HSP70 protein-containing neurons in the cortical "penumbra" and hippocampus survive ischemic injury and are "reversibly injured." It is shown that CA1 hippocampal pyramidal neurons die or are reversibly injured in approximately 50% of animals following permanent MCA occlusions. Although the mechanism of this hippocampal injury is unknown, it could relate to transynaptic activation of N-methyl-D-aspartate (NMDA) receptors that mediate induction of early genes in hippocampus.

Deletion of Aldose Reductase Leads to Protection against Cerebral Ischemic Injury

“…In our AR studies, all mice were of C57BL/6 background as the AR À/À mice were backcrossed to the C57BL/6N strain to the 11th generation (N11), and therefore C57BL/6N mice were used as controls. Secondly, it is also possible that breakdown of the blood-brain barrier in the ipsilateral side contributed to a widespread brain damage after transient ischemia (States et al, 1996).…”

Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases

“…The same physiological parameters also were monitored for rats in other groups and no significant difference was noticed among them as well. (States et al, 1996), it is often not considered an ischemic penumbral or ischemic core area. Interestingly, isoflurane preconditioning reduced this ischemia-induced delayed cell loss in the ischemic penumbra.…”

Presumed apoptosis and reduced arcuate nucleus neuropeptide Y and pro-opiomelanocortin mRNA in non-coma hypoglycemia.

“…Finally, there was no evidence that the cells in this or any other brain area induced HSP-72 expression, which is often found in damaged cells that are destined to survive their injury (35). The induction of HSP-72 is thought to confer a degree of protection and it is rarely seen in cells undergoing apoptosis or necrosis (36,37). However, severe hypoglycemia does induce HSP-72 in both neurons (35) and astrocytes (36).…”