Transient cerebral ischemia (TCI) is one of the most common causes of vascular dementia (VaD) which is known as an etiological factor in the development of Alzheimer’s disease (AD). It can induce profound neurodegeneration; reflecting severe cognitive deficits. It is clear that TCI may generate reactive oxygen species and stimulate an inflammatory response in the hippocampus. However, despite extensive consideration, the actual molecular mechanism of the neurodegeneration has remained elusive thus far. Moreover, there is currently no effective, approved pharmacological treatment for vascular dementia. We herein employed cerebral hypoperfusion mouse model and examined tau pathology and neurodegeneration in the animals. We observed prominent tau pathology in the brain associated with cognitive decline. Importantly, we found that pathogenic cis p-tau removal using respective mouse monoclonal antibody, prevented mice from developing cognitive dysfunction as well as brain ultrastructural destruction caused by TCI. These results strongly suggest that TCI triggers tau pathogenicity, which may lead to comprehensive neurodegeneration. Also, our findings suggest an efficient therapeutic target to fight with the devastating disorder.

Barnes maze test was performed to assess the spatial learning and memory performance in experimental animals after TCI and reperfusion ischemia. (A) Escape latencies in training days in differences among groups. (B) Primary latency (sec) at probe day. (C) The time (s) spent in the target quadrant and (D) the frequency of entries in the zone–platform in different groups. (E) Representative traces display the sample paths of the mice from the maze during the probe trials. Data are represented as mean ± SE (n=6) per group, *P < 0.05 vs. sham, #P < 0.05 vs. ischemic group. IgG, Immunoglobulin G; Ab, antibody; TCI, Transient cerebral ischemia; Fer, Frequency.