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Growing evidence suggests that reduced cerebral blood flow contributes to cognitive decline in ageing and dementia. Attwell and colleagues discuss the underlying mechanisms and functional consequences of vascular dysfunction in ageing, Alzheimer disease and vascular dementia, and consider the implications for therapeutic interventions.

Coronary 'no-reflow' is a substantial clinical problem, even after successful percutaneous coronary intervention for myocardial infarction. In this Perspectives, article, O'Farrell and Attwell describe the similarities between this phenomenon and no-reflow in the brain after ischaemic stroke, and propose that pericytes contribute to the underlying pathophysiology in both situations. Cardiac pericytes might, therefore, be a novel therapeutic target for coronary no-reflow.

How and to what extent oligodendrocytes (OLs) contribute to learning and cognition is not well understood. Here, the authors show that the performance of mice in working memory-dependent cognitive tasks depends on OL genesis and is proportional to the number of OL precursors and OLs generated during training.

Neuronal activity relaxes pericytes, leading to capillary dilation and increased blood flow, before arterioles dilate, suggesting that pericytes initiate blood-oxygen-level-dependent (BOLD) functional imaging signals; pericytes constrict and die in rigor in ischaemia, which will cause a long-lasting blood flow decrease after stroke, and damage the blood–brain barrier.

Ischaemia damages nerve myelin by depriving neurons and their myelinating oligodendrocytes of oxygen and glucose; here it is shown that ischaemic damage is caused through the H⁺-dependent activation of TRPA1 channels, and not via glutamate receptors of the NMDA type, as previously thought, providing a new mechanism and promising therapeutic targets for diseases as diverse and prevalent as cerebral palsy, spinal cord injury, stroke and multiple sclerosis.

The importance of neurotransmitter release by astrocytes is highly controversial. Hamilton and Attwell review evidence for the release of glutamate,D-serine and ATP by astrocytes and their role in shaping synaptic activity. Potential mechanisms of astrocyte neurotransmitter release, including regulated exocytosis, are assessed.

Early in Alzheimer’s disease (AD), brain blood flow is reduced by pericytes constricting capillaries. Korte et al. show that oral nimodipine can reverse this and decrease brain hypoxia. Blocking capillary constriction is a potential add-on therapy in AD.

Longden et al. demonstrate that brain capillaries function as a vast sensory web, monitoring neuronal activity by sensing K⁺ and translating this into a K_IR-channel-mediated regenerative retrograde hyperpolarizing signal that propagates to upstream arterioles to drive vasodilation and an increase in blood flow into the capillary bed.

Microglia are the brain’s immune cells. A previously unknown role for microglia has now been uncovered: providing negative feedback to active neurons, to help the brain process information.

The brain relies on blood to supply oxygen and glucose for energy. Surprisingly, neuronal activity, acting via supporting cells called astrocytes, can increase or decrease blood flow depending on whether oxygen levels are low or high.

Are astrocytes merely housekeeping cells that maintain constant the environment of neurons or are they important for CNS information processing? Intense debate over the function of calcium signaling in astrocytes will increase with the discovery of a previously unknown mechanism by which astrocyte [Ca²⁺]_i is regulated.

The role of transient elevations of the intracellular concentration of calcium in astrocytes is controversial. Some neuroscientists believe that, by triggering the release of 'gliotransmitters', astrocyte calcium transients regulate synaptic strength and neuronal excitability, while others deny that gliotransmission exists. Bazargani and Attwell assess the status of this rapidly evolving field.

Action potential timing is fundamental to information processing, but its determinants are not fully understood. Here the authors demonstrate unexpected structural specializations of myelinated axons in the auditory brainstem that help to adjust action potential arrival time for sound localization.

The diagnosis of Budd–Chiari syndrome (BCS) is made difficult by its wide spectrum of presentations and the varying severity of liver damage seen in these patients. In addition, prognosis defined by the traditional BCS classification—as fulminant, acute or chronic—makes assessing therapeutic benefit more difficult. This Review highlights advances in the classification, prognosis and therapy of BCS.

Active neurons increase their energy supply by dilating nearby arterioles and capillaries to increase blood flow, but the mechanisms underlying neurovascular coupling are debated. In this paper, the authors show that different calcium-dependent signaling pathways regulate blood flow at the level of capillary pericytes and arteriole smooth muscle.

In computationally active areas of the brain, the blood flow is increased to provide more energy to nerve cells. New data fuel the controversy over how this energy supply is regulated.

Chemokine signaling releases glutamate from astrocytes. This process can be amplified by microglia, inducing neurotoxicity, and activated by the HIV coat protein gp120.

Myelin formed by oligodendrocytes enables rapid, energy-efficient information transmission in CNS, but its development is unclear. The authors show that the rate of intracellular calcium transients regulates elongation of developing myelin sheaths.

Transition-metal single-atom catalysts display excellent activity per metal atom site, but suffer from low metal atom densities (typically less than 5 wt% or 1 at.%), which limits their overall catalytic performance. Now, the use of a graphene-quantum-dot primary support, later interweaved into a carbon matrix, has enabled the synthesis of single-atom catalysts with high transition-metal atom loadings of up to 40 wt% or 3.84 at.%.

The authors find that GABA_AR-mediated tonic currents recorded in rodent cerebellar granules cells can be modulated by ethanol in opposite directions in different strains exhibiting opposite preferences in alcohol consumption. These differences in ethanol sensitivity across strains are linked to differential levels of expression of presynaptic neuronal nitric oxide synthase and postsynaptic PKC activity.