Acute Hypertension Induces Oxidative Stress in Brain Tissues

Abstract

Arterial hypertension is not only a major risk factor for cerebrovascular accidents, such as stroke and cerebral hemorrhage, but is also associated to milder forms of brain injury. One of the main causes of neurodegeneration is the increase in reactive oxygen species (ROS) that is also a common trait of hypertensive conditions, thus suggesting that such a mechanism could play a role even in the onset of hypertension-evoked brain injury. To investigate this issue, we have explored the effect of acute-induced hypertensive conditions on cerebral oxidative stress. To this aim, we have developed a mouse model of transverse aortic coarctation (TAC) between the two carotid arteries, which imposes acutely on the right brain hemisphere a dramatic increase in blood pressure. Our results show that hypertension acutely induced by aortic coarctation induces a breaking of the blood-brain barrier (BBB) and reactive astrocytosis through hyperperfusion, and evokes trigger factors of neurodegeneration such as oxidative stress and inflammation, similar to that observed in cerebral hypoperfusion. Moreover, the derived brain injury is mainly localized in selected brain areas controlling cognitive functions, such as the cortex and hippocampus, and could be a consequence of a defect in the BBB permeability. It is noteworthy to emphasize that, even if these latter events are not enough to produce ischemic/hemorrhagic injury, they are able to alter mechanisms fundamental for maintaining normal brain function, such as protein synthesis, which has a prominent role for memory formation and cortical plasticity.

Role of 90-kDa Heat Shock Protein (Hsp 90) and Protein Degradation in Regulating Neuronal Levels of G Protein-Coupled Receptor Kinase 3

“…However, under excessive electrical activation and depolarization, associated with increased in- jpet.aspetjournals.org tracellular calcium accumulation, GRK3 levels and ␣ 2 -AR desensitization would be reduced, permitting maximum neuroprotection. Oxidative stress is a common trait of hypertension and plays an important role in hypertension-evoked brain injury by increasing the tissue concentrations of neurotransmitters and increasing cellular calcium ions influx (Nishigaya et al, 1991;Brown et al, 2004;Poulet et al, 2006). Therefore, calpain activation could cause increased degradation of GRK3 and render the ␣ 2 -AR resistant to desensitization by norepinephrine and EPI.…”

Angiotensin II Modulates BBB Permeability via Activation of the AT1 Receptor in Brain Endothelial Cells

“…Prolonged hypertension is a risk factor for cerebrovascular, cardiovascular, retinal, and end-stage renal diseases, whereas acute increases in blood pressure can be life threatening, leading immediately to organ dysfunction and permanent damage (AHA, 2008;Poulet et al, 2006). Severe acute changes in blood pressure are categorized as hypertensive emergencies when they are associated with end organ damage (cardiovascular, cerebrovascular, retinal, or renal).…”

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

“…Estrogen is a known antioxidant [15,32,33] and has been reported to inhibit membrane lipid peroxidation [2], thereby possibly attenuating the increased BBB permeability caused by free radical generation that is known to occur during acute hypertension and other brain injuries [41,50]. However, given that the level of estrogen in the OVX+E group was greater than CTL, estrogen replacement would be expected in this case to have a greater antioxidant effect and restore permeability to control levels.…”