Accumulation of Amyloid Beta (Aβ) Peptide on Blood Vessel Walls in the Damaged Brain after Transient Middle Cerebral Artery Occlusion. Martins Antonio Henrique,Zayas-Santiago Astrid,Ferrer-Acosta Yancy,Martinez-Jimenez Solianne M,Zueva Lidia,Diaz-Garcia Amanda,Inyushin Mikhail Biomolecules It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke. Considering that they have been shown to form ion channels in cells, affecting osmotic balance, we used an Aβ peptide channel blocker, tromethamine (2-amino-2-(hydroxymethyl) propane-1,3-diol), to prevent this additional injury. Tromethamine injected 0.1 g/100 g body weight intraperitoneally at 5 min before tMCAO decreased water content in the damaged hemisphere, as measured by dry brain weight. Congo red staining, which binds only to Aβ oligomer plaques (amyloid), showed that there was no significant presence of plaques. Therefore, we suggest that Aβ peptide oligomers are responsible for some of the brain damage during stroke and that blockage of the ion channels that they form could be beneficial in treating this complex neurological syndrome. 10.3390/biom9080350

Hypoxia enhances beta-amyloid-induced apoptosis in rat cultured hippocampal neurons. Egashira Nobuaki,Iwasaki Katsunori,Ishibashi Motoki,Hatip-Al-Khatib Izzetin,Wolozin Benjamin,Mishima Kenichi,Irie Keiichi,Fujiwara Michihiro Japanese journal of pharmacology We investigated the effect of hypoxia on beta-amyloid (Abeta)-induced apoptosis in rat cultured hippocampal neurons. Abeta (25 microM for 48 h) decreased the number of neuronal cells and increased the number of TUNEL-positive cells. Hypoxia (6 h) also decreased the number of neuronal cells, but did not increase the number of TUNEL-positive cells. Moreover, combined treatment with both Abeta and hypoxia (Abeta/hypoxia) significantly enhanced the decrease in the number of neuronal cells and the increase in the number of TUNEL-positive cells. Z-Asp-CH(2)-DCB, an inhibitor of interleukin-1beta-converting enzyme (ICE), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, decreased the number of TUNEL-positive cells with Abeta/hypoxia. These findings suggest that ischemia or hypoxia is an important factor that facilitates the symptoms of Alzheimer's disease and that non-NMDA receptors are involved in the induction of apoptosis in patients suffering from both cerebrovascular disease and Alzheimer's disease.

Hypoxia induces beta-amyloid in association with death of RGC-5 cells in culture. Li Juan,Dong Zhizhang,Liu Bingqian,Zhuo Yehong,Sun Xuerong,Yang Zhikuan,Ge Jian,Tan Zhiqun Biochemical and biophysical research communications Beta-amyloid (Aβ) derived from amyloid precursor protein (APP) has been associated with retinal degeneration in Alzheimer's disease (AD) and glaucoma. This study examined whether hypoxia exposure induces Aβ accumulation in RGC-5 cells. While levels of APP mRNA and protein significantly increased in the cells, elevated abundance of Aβ was also observed in cells and culture medium between 12 or 24 and 48h after 5% O(2) hypoxia treatment. Additionally, there is a close relationship between induction of APP and Aβ and intracellular accumulation of ROS along with loss of mitochondrial membrane potential followed by the death of RGC-5 cells in culture under hypoxia. These results suggest a possible involvement of APP and Aβ in the death of RGCs challenged by hypoxia. 10.1016/j.bbrc.2011.05.101