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Astrocytes could have a pivotal role inthe mediation of vasodilation and, assuch, have been implicated inpathological processes associated withabnormal control of cerebralmicrocirculation.

Local increase in blood flow inresponse to neural activity is a keycharacteristic of brain function, butthe underlying mechanisms arepoorly understood. Previous studiesinvestigating the role of astrocytes inhyperaemia have produced conflictingresults, probably because of the use ofnon-perfused brain tissue, which doesnot accurately represent the in-vivoenvironment. Now, researchers from

the University of Rochester MedicalSchool (New York, USA), have soughtto define the role of astrocytes in thecontrol of local microcirculation in vivo(Nat Neurosci 2005; published onlineDec 25. DOI:10.1038/nn1623).

Takahiro Takano and colleaguesdirectly imaged the activity ofastrocytes labelled with the calciumsensitive indicator rhod-2 in exposedsomatosensory cortices of anaes-thetised adult mice. The team, leadby principal investigator MaikenNedergaard, showed that calciumelevations triggered in astrocyticendfeet, either by direct stimulationthrough photolysis of a calcium cagedcompound or by stimulation ofneuronal afferents, results in thedilation of the cerebral corticalarterioles.

Because at least four potentialpathways of astrocyte-based vaso-dilation exist, Nedergaard andcolleagues aimed to define theintracellular signalling pathway bywhich astrocytes mediate hyperaemia.Their findings accord with those ofprevious work done by GiorgioCarmignoto (CNR Institute ofNeuroscience, University of Padova,Padova, Italy) and colleagues. “As in

our experiments in slices, the authorsfind that the astrocytic action isimpaired in the presence ofindomethacin and of a more specificinhibitor of COX1”, commentsCarmignoto. “Together with theobservation that prostaglandin E2, aswe previously observed in cortical slicepreparations, induces arterioledilation, these data confirm a key roleof astrocytes that, through the releaseof COX1 product, mediate neuronalactivity-dependent dilation of cerebralarterioles.”

The team’s findings implicateastrocytes in the cause anddevelopment of brain pathologies,such as stroke, hypotension, andAlzheimer’s disease, and as a potentialnovel treatment target. Furthermore,if astrocytes rather than neuronsindeed control blood flow “the tightrelationship between blood flow andactivity might be altered inpathological disorders, and change inflow depicted by functional imagingtechniques might reflect themalfunction of astrocytes rather thanthe change of neural activity”, explainsTakano.

Laura Thomas

208 http://neurology.thelancet.com Vol 5 March 2006

Astrocytes implicated in control of cerebral blood flow

T cells and microglial activity mighthave important roles in hippocampalneurogenesis and spatial learningabilites in adulthood. In a new study,researchers showed that hippocampalneurogenesis was significantly im-paired in immune-deficient mice. Thisimpairment resolved when CNS-specific T cells were introduced. Theauthors also reported that these T cellscontribute to the maintenance ofcognitive ability throughout adultlife(Nat Neurosci 2006; 9: 268–75).

“From a clinical perspective, theresults of our study suggest that age-related cognitive decline, neuro-

degenerative disorders (such asAlzheimer’s, Parkinson’s, and LouGehrig’s diseases), and even somepsychiatric disorders such as majordepression, can be perceived in abroader context, which takes thesystemic immune system intoaccount”, Michal Schwartz (WeizmannInstitute of Science, Rehovot, Israel)told The Lancet Neurology.

Rats kept in an environment richwith opportunities for enhancedmental and physical activity have anincreased capacity for hippocampalneurogenesis. In Schwatz andcolleagues’ study adult rats were kept

in an enriched environment or instandard cages (control) for 6 weeks.The rats received a course of injectionsof bromodeoxyuridine (BrdU) fordetection of new cells. After 1 week,the hippocampi of the rats wereexamined with antibodies to BrdU, aneuronal marker, and a microglialmarker. The rats kept in an enrichedenvironment had notably more newlyformed neurons and microglia in thedentate gyri compared with thecontrol rats.

In a separate part of thestudy immune-deficient mice hadsignificantly fewer newly formed

Can a good immune system reduce ageing?

Do astrocytes control blood flow?

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to the printed journal.