星形胶质细胞和神经损伤(4)

星形胶质细胞的选择性调控

CONCLUSION

During evolution, neurons have lost many essential metabolic pathways as they became

increasingly specialized and gained the ability to generate action potentials and communicate

by synaptic transmission. As a consequence, neurons in the adult brain depend on metabolic

support from surrounding astrocytes. For example, neurons do not express the mitochondrial

enzyme glutamine dehydrogenase and cannot produce the chief excitatory transmitter,

glutamate, which in the adult CNS mediates 70% of neurotransmission. Since glutamate does

not pass through the blood-brain-barrier, excitatory transmission heavily depends on glutamate

produced by astrocytes 33. Similarly, synapse formation requires multiple lipids, including

cholesterol, produced by astrocytes 47. It is clear that neuron survival in both the normal and

the diseased brain relies heavily on surrounding astrocytes. A striking example is ischemic

infarcts, in which neurons do not survive if neighboring astrocytes are lost. While large gaps

exist with regard to our understanding of how ischemia affects the supportive function of

astrocytes, it is likely that failure of glutamate uptake, K+ buffering, water homeostasis,

vascular control, etc, all contribute to the massive loss of neurons in focal stroke. A challenge

for the future is to develop experimental tools to manipulate and monitor dynamic changes in

the supportive function in ischemic astrocytes.NIH-PA Author Manuscript

NIH-PA Author Manuscript

NIH-PA Author ManuscriptAcknowledgementThis work was supported by the National Institutes of Health Grants, NS38073, NS39559, and NS050315 and theAdelson Program in Neural Repair and Regeneration.References1. Haydon PG. Glia: Listening and talking to the synapse. Nat Rev Neurosci 2001;2:185–193. [PubMed:11256079]2. Volterra A, Meldolesi J. Astrocytes, from brain glue to communication elements: The revolution

continues. Nat Rev Neurosci 2005;6:626–640. [PubMed: 16025096]

3. Nedergaard M. Direct signaling from astrocytes to neurons in cultures of mammalian brain cells.

Science 1994;263:1768–1771. [PubMed: 8134839]

4. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG. Glutamate-mediated astrocyte-

neuron signalling. Nature 1994;369:744–747. [PubMed: 7911978]

5. Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: Glia, the unacknowledged partner.

Trends Neurosci 1999;22:208–215. [PubMed: 10322493]205_00001349

6. Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: Redefining the functional

architecture of the brain. Trends Neurosci 2003;26:523–530. [PubMed: 14522144]

7. Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G. Neuron-

to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci

2003;6:43–50. [PubMed: 12469126]

8. Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X, Nedergaard M. Astrocyte-mediated control

of cerebral blood flow. Nat Neurosci 2006;9:260–267. [PubMed: 16388306]

9. Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci

2007;10:1369–1376. [PubMed: 17965657]

10. Nedergaard M, Astrup J, Klinken L. Cell density and cortex thickness in the border zone surrounding

old infarcts in the human brain. Stroke 1984;15:1033–1039. [PubMed: 6209831]

11. Nedergaard M. Neuronal injury in the infarct border: A neuropathological study in the rat. Acta

Neuropathol 1987;73:267–274. [PubMed: 3618118]

12. Nedergaard M. Mechanisms of brain damage in focal cerebral ischemia. Acta Neurol Scand

1988;77:81–101. [PubMed: 3284272]

13. Chen Y, Swanson RA. Astrocytes and brain injury. J Cereb Blood Flow Metab 2003;23:137–149.

[PubMed: 12571445]