Extravasation of albumin across the BBB 20 min after-MCAO. The aged animals exhibited greater BBB permeability in relation to the corresponding young rats in the infarcted hemisphere (P < 0.001). (Copyright: DiNapoli et al. [107]).

Acute cerebral ischemia and neuroinflammation. Acute stroke triggers an inflammatory cascade via the activation of a number of molecular mediators. The initial phase is associated with the generation of reactive oxygen species (ROS) within the ischaemic cerebral tissue. This is followed by the release of inflammatory cytokines and chemokines, which subsequently results in activation of resident microglia and upregulation of cell adhesion molecules (CAMs). The chemokines are involved in the mobilisation of leukocytes, and these inflammatory cells then interact with the CAMs. This leads to leukocyte infiltration of the ischaemic tissue (diapedesis), which further exacerbates the inflammatory process. Activation of nuclear factor kappa-B (NF-κB) and inducible nitric oxide synthase (iNOS) results in increased oxidative stress and further cytokine activation. Release of matrix metalloproteinases (MMPs) from astrocytes and microglia leads to blood-brain barrier (BBB) dysfunction, cerebral oedema, and neuronal cell death. The aging process further exacerbates these neuroinflammatory pathways, and this has been associated with increased cognitive decline and poor functional outcome in elderly stroke patients. Therapeutic targeting of these molecular pathways is an important area of translational medicine research in cerebrovascular disease.