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[P2.44]: Role of Mst3b/STK24 in axon outgrowth during development and recovery from perinatal brain injury
Author(s) -
Irwin N.,
Frederick N.,
Wu S.,
Pinada A.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.174
Subject(s) - medical school , citation , library science , medicine , psychology , medical education , computer science
Premature infants often suffer from brain injury leading to severe cognitive and motor disability. The most common neuropathological lesion underlying cerebral palsy in premature infants is periventricular leukomalacia (PVL), a focal necrosis involving astrocytes, oligodendocytes and microglia. Up to 10% of these infants with very low birth weight have cerebral palsy and approximately 50% have cognitive dysfunction. This “encephalopathy of prematurity” is likely to be a combination of a primary insult, followed by secondary injury over time. However, PVL has recently been recognized to involve damage to axons. Therefore, understanding control of axon growth during development and after perinatal injury is essential to discovery of treatments for early brain injury. Axon growth (Irwin et al. 2006) and regeneration (Lorber et al., 2009) in adult rats is controlled by the kinase Mst3b. Activation of Mst3b leads to partial recovery from stroke (Benowitz et al., 1999). Mst3b controls activation of B-raf in young cortical neurons leading to outgrowth of axons. We are further characterizing this pathway and analyzing the role of Mst3b in axon regeneration in a newly developed in vitro assay of early postnatal axon damage. Activation of Mst3b by inosine, hypoxanthine, and other purines stimulates axon regeneration from these young neurons. Further understanding of Mst3b will enhance the possibilities for treatment of brain injury in premature infants.