Normally, cerebral blood flow (CBF) is maintained by cerebral autoregulation at about 50 mL blood/100 g brain/min. In acute ischaemic stroke, a cerebral artery is occluded or there is a reduction in perfusion distal to a severe stenosis, resulting in focal brain ischaemia and infarction. As the regional CBF falls, the regional lack of oxygen and glucose results in a time-and flow-dependent cascade characterized by a fall in energy (adenosine triphosphate [ATP]) production. Neuronal function is affected in two stages. The first threshold is at a blood flow of about 20 mL blood/100 g brain/min, below which neuronal electrical function is compromised, generating clinical deficits, but cellular homeostasis is maintained and recovery remains possible. However, if blood flow falls below the second critical threshold of 10 mL blood/100 g brain/min, an ‘ischaemic cascade’of injurious molecular events is triggered (Doyle et al., 2008; Sekerdag et al., 2018). Free radicals are generated. There is excessive release and impaired reuptake of excitatory amino acid (EAA) neurotransmitters such as glutamate, causing overstimulation of neuronal glutamate receptors (excitotoxicity), aerobic mitochondrial metabolism fails, inefficient anaerobic metabolism of glucose takes over, and harmful lactic acidosis evolves. Energydependent homoeostatic mechanisms of maintaining cellular ions fail, potassium leaks out of cells, and sodium, water, and calcium enter cells, leading to cytotoxic oedema and calcium-induced mitochondrial failure, respectively. If severe ischaemia (blood flow below 10 mL blood/100 g brain/min) is sustained, irreversible neuronal damage occurs and neuronal cell apoptosis and necrosis ensue.