Acute hypertension induces oxidative stress in brain tissues.
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.
Poulet
Roberta
R
Department of Angio-Cardio-Neurology, IRCCS Neuromed, Pozzilli (IS), Italy.
Gentile
Maria T
MT
Vecchione
Carmine
C
Distaso
Maria
M
Aretini
Alessandra
A
Fratta
Luigi
L
Russo
Giovanni
G
Echart
Cinara
C
Maffei
Angelo
A
De Simoni
Maria G
MG
Lembo
Giuseppe
G
D000208:Acute Disease; D000818:Animals; D001017:Aortic Coarctation / Q000503:physiopathology; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002525:Cerebellar Cortex / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*
D016207:Cytokines; D019255:NADPH Oxidases