Editorial MechanismsofPerinatalBrainInjurydownloads.hindawi.com/journals/nri/2012/157858.pdf · 2...

Hindawi Publishing CorporationNeurology Research InternationalVolume 2012, Article ID 157858, 2 pagesdoi:10.1155/2012/157858

Editorial

Mechanisms of Perinatal Brain Injury

Robin L. Haynes,1 Tara M. DeSilva,2 and Jianrong Li3

1 Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA2 Departments of Physical Medicine and Rehabilitation and Neurobiology, Center for Glial Biology in Medicine,University of Alabama at Birmingham, Birmingham, AL 35294, USA

3 Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA

Correspondence should be addressed to Robin L. Haynes, robin.haynes@childrens.harvard.edu

Received 30 April 2012; Accepted 30 April 2012

Copyright © 2012 Robin L. Haynes et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

The guest editors of this journal are pleased to introduce thisspecial issue on the mechanisms of perinatal brain injury.The purpose of this issue is to highlight recent developmentstoward our understanding of both grey and white matterinjury in the perinatal brain. Over the last decade, therehas been significant advancement in our understanding ofthe mechanisms underlying this injury. The progressionof the field stems from many factors including: (1) thedevelopment and refinement of experimental models; (2)advances in modern imaging technologies, such as magneticresonance imaging and diffusion tensor imaging; (3) detailedcharacterization of the injury, both in human and animals,on the anatomical, cellular, and subcellular levels and (4)identification of the developmental factors that underlie thevulnerability of the perinatal brain to such injury. Here wepresent nine review and two research articles that togetherhighlight these advancements, as summarized below. It hasbeen our honor to work with each of the contributingscientists, and we thank them for their commitment to thisSpecial Issue.

The review by C. Thornton et al. summarizes our currentunderstanding of the “Molecular mechanisms of perinatalbrain injury,” with a focus on mitochondrial functionalimpairment and apoptotic events during the secondaryinjury phase. The authors also present the most up-to-dateintervention strategies targeting the different stages of braininjury.

V. Ten and A. Starkov further explore the role ofmitochondria in hypoxic-ischemic (H-I) injury and pro-vide evidence for the mitochondrial production of reactiveoxygen species as a pathogenic mechanism underlyingthis injury. The authors summarize experimental data

delineating mitochondrial sources of reactive oxygen speciesand their specific targets in neonatal animals.

Necrotic cell death is well documented in H-I braininjury and is traditionally thought uncontrollable. In anotherreview, R. Chavez-Valdez et al. introduce the recentlyidentified RIP1/3 kinase dependent programmed necrosispathway to the field of neonatal brain injury and proposean apoptosis-necrosis cell death “continuum” for cellulardegeneration. The authors highlight experimental evidencesupporting a prominent role of programmed necrosis inneonatal H-I brain injury.

Another paper by C. Hill and R. Fitch explores theunderlying basis of the increased vulnerability of male infantsto H-I injury and their increased incidence of cognitivedeficits associated with that injury. The authors discusshormonal factors underlying these differences as well as sex-specific differences in H-I-induced cell death pathways.

In the review by K. Buller et al., the effects of perinatalH-I injury on the serotonergic system are summarized.The potential use of anti-inflammatory interventions toalleviate this injury is also discussed. Disruption of thisneurotransmitter system may underlie the cardiorespiratory,cognitive, and attention deficits observed in survivors ofprematurity.

Changing the focus from H-I injury to inflammation andinfection, C. Mallard and X. Wang summarize clinical andexperimental evidence for neonatal sepsis and increased vul-nerability of the immature brain and discuss the involvementof Toll-like receptors (TLRs) in perinatal brain injury.

Continuing in the area of inflammation and infection, R.McAdams and S. Juul address the initiation and activation ofcytokines and inflammatory cells in the perinatal brain and

2 Neurology Research International

their detrimental short and long-term consequences. Theyhighlight the importance of understanding the dynamicstructure of the blood brain barrier, as well as the relativelyunknown mechanisms that impair its integrity allowingimmune cells direct access to the brain.

In the first of two research articles, D. Selip et al. char-acterize, in a rodent model of H-I, the spectrum of greymatter damage in association with the white matter damageonce thought to be dominant in H-I injury. The authorscharacterize the regional susceptibility to H-I injury in termsof the inflammatory response, white matter injury andmyelin loss, neuronal degeneration, and axonal injury.

Our second research article by K. Shrivastava et al. pro-vides an extensive characterization of the glia/inflammatoryresponse following H-I using a common model of injurythought to spare the contralateral hemisphere. This studyextends our knowledge of this model by characterizing asubtle inflammatory response in the contralateral brain, andprovides important information regarding the timing ofthe insult in relationship to the initiation of inflammatorysignaling cascades.

The paper by V. Biran et al. highlights a novel area of thebrain—the cerebellum—that has emerged as an importantattribute of perinatal brain injury through imaging stud-ies. This review provides an extensive detailed analysis ofcerebellar development, and the implications of disruptingits normal maturation as a consequence of perinatal braininjury.

Finally H. Kinney and J. Volpe stress the importance ofdeveloping and using animal models with a careful consid-eration of human perinatal brain development and injury.This paper emphasizes the need to model perinatal braininjury as an encephalopathy of prematurity characterized bya combination of both grey and white matter lesions.

Acknowledgment

Lastly we would like to remember a colleague in the fieldand the senior author of the article by Shrivastava et al.described above. Dr. Laia Acarin made many significantcontributions to our field of perinatal brain injury. Herwork in excitotoxicity and H-I has yielded valuable insightinto the glial and inflammatory responses following neonatalbrain damage, as well as the mechanisms controlling thisinflammation. We would like to respectfully dedicate thisspecial issue to her memory.

Robin L. HaynesTara M. DeSilva

Jianrong Li

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