title: Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth.
abstract: Cerebral palsy is one of the most devastating consequences of brain injury around the time of birth, and nearly a third of cases are now associated with premature birth. Compared with term babies, preterm babies have an increased incidence of complications that may increase the risk of disability, such as intraventricular hemorrhage, periventricular leukomalacia, sepsis, and necrotizing enterocolitis. The response to injury is highly dependent on brain maturity, and although cellular vulnerability is well documented, there is now evidence that premyelinating axons are also particularly sensitive to ischemic injury. In this review, we will explore recent evidence highlighting a central role for glia in mediating increased risk of disability in premature infants, including excessive activation of microglia and opening of astrocytic gap junction hemichannels in spreading injury after brain ischemia, in part likely involving release of adenosine triphosphate (ATP) and overactivation of purinergic receptors, particularly in white matter. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious circle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing effective neuroprotective strategies for preterm infants requires a detailed understanding of glial responses.
authors: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Carina
authors: C
authors: Mallard
authors: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors: Joanne O
authors: JO
authors: Davidson
authors: Department of Pediatrics, NorthShore University Health System and University of Chicago, Evanston, Illinois.
authors: Sidhartha
authors: S
authors: Tan
authors: Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
authors: Colin R
authors: CR
authors: Green
authors: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors: Laura
authors: L
authors: Bennet
authors: Institute of Women's Health, University College London, London, UK.
authors: Nicola J
authors: NJ
authors: Robertson
authors: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors: Alistair Jan
authors: AJ
authors: Gunn
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002547:Cerebral Palsy / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017630:Connexins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D018836:Inflammation Mediators / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D047928:Premature Birth; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D017630:Connexins; D018836:Inflammation Mediators; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate