Nerve regeneration – A dual role for reactive astrocytes
Although the ability of the adult mammalian CNS to regenerate is poor, temporary functional recovery is often observed soon after spinal cord injury (SCI). The mechanism underlying this phenomenon is unclear. Writing in Nature Medicine, Okada and colleagues show that astrocytic responses are important for tissue repair and recovery of motor function following injury.
In the injured CNS, reactive astrocytes form dense scar tissues — the glial scar — around the lesion site, and this serves to compact inflammatory cells and re-seal the blood–brain barrier after it has been broken by injury. To regenerating axons, the glial scar is bad news and represents an insurmountable molecular and physical barrier. In mice, the glial scar is formed around 14 days after SCI, which coincides with the peak of functional improvement.
Do the initial astrocytic responses have a role in functional recovery in the early phase following injury? To address this issue, the researchers generated mice with defective astrocytic responses. The mice had selective deletion of either Stat3 (signal transducer and activator of transcription 3) or its inhibitor Soc3 (suppressor of cytokine signalling 3) in reactive astroctyes. STAT3 is thought to mediate a variety of biological processes, such as wound healing and cellular migration, and is a downstream effector molecule of several cytokines involved in regulating astrogliosis.
Okada et al. show that, in normal mice, phosphorylation (and therefore activation) of STAT3 in the spinal cord was markedly increased 12 hours after injury.