Brain bioenergetics in chronic hypertension: Risk factor for acute ischemic stroke

Chronic hypertension is one of the key modifiable risk factors for acute ischemic stroke, also contributing to determine greater neurological deficits and worse functional outcome when an acute cerebrovascular event would occur. A tight relationship exists between cerebrovascular autoregulation, neuronal activity and brain bioenergetics. In chronic hypertension, progressive adaptations of these processes occur as an attempt to cope with the demanding necessity of brain functions, creating a new steady-state homeostatic condition. However, these adaptive modifications are insufficient to grant an adequate response to possible pathological perturbations of the established fragile hemodynamic and metabolic homeostasis. In this narrative review, we will discuss the main mechanisms by which alterations in brain bioenergetics and mitochondrial function in chronic hypertension could lead to increased risk of acute ischemic stroke, stressing the interconnections between hemodynamic factors (i.e. cerebral autoregulation and neurovascular coupling) and metabolic processes. Both experimental and clinical pieces of evidence will be discussed. Moreover, the potential role of mitochondrial dysfunction in determining, or at least sustaining, the pathogenesis and progression of chronic neurogenic hypertension will be considered. In the perspective of novel therapeutic strategies aiming at improving brain bioenergetics, we propose some determinant factors to consider in future studies focused on the cause-effect relationships between chronic hypertension and brain bioenergetic abnormalities (and vice versa), so to help translational research in this so-far unfilled gap.