Hanyang Med Rev.  2009 Nov;29(4):370-378. 10.7599/hmr.2009.29.4.370.

Prevention and Therapeutic Strategies for Brain Injury in Extreme Prematurity

• Park HK

• KMID: 2053724
• DOI: http://doi.org/10.7599/hmr.2009.29.4.370

Abstract

As the evolution of neonatal intensive care has resulted in dramatic improvements in the survival of extremely preterm infants, there is major concern about the increasing rates of neurodisability among those at the limits of viability. Among the infants with parenchymal brain injury such as intraventricular hemorrhage grades III-IV, ventriculomegaly and cystic periventricular leukomalacia, more than 1 out of 3 have one of the cerebral palsy syndrome. However, research examining neuroprotection for brain injury in extremely preterm infants is limited. This review was focused on brain injury and recent strategies for neuroprotection addressing both white matter injury and gray matter dysfunction in infants born <26 weeks' gestation and/or with birth weight less than 750 g.

Keyword

Extreme prematurity; Brain injury; Therapeutic strategies

MeSH Terms

Birth Weight
Brain
Brain Injuries
Cerebral Palsy
Hemorrhage
Humans
Infant
Infant, Extremely Premature
Infant, Newborn
Intensive Care, Neonatal
Leukomalacia, Periventricular
Pregnancy

Figure

• 

  Fig. 1 Schematic diagram of the three major forms of white matter abnormality in premature infants. Cystic (A1, A2) and non-cystic (B) PVLexhibit the two components of the lesion-that is, focal necrosis deep in the white matter and more diffuse injury characterised by a loss of pre-oligodendrocytes and marked astrogliosis. In cystic disease (A1, A2) the focal necrotic lesions are macroscopic and evolve to cysts, whereas in non-cystic disease (B) the focal lesions are microscopic and evolve to glial scars. Diffuse white matter gliosis (DWMG) (without focal necrosis) (C1, C2) may represent the mildest form of the spectrum of cerebral white matter injury.(From Khwaja O, Volpe JJ8)

• 

  Fig. 2 Imaging of infants with IVH grades III & IV. A, Sonographic image of an infant with IVH grade III born at GA 24+6 weeks and scanned at 35 weeks. B, Image of an infant with IVH grade IV born at GA 25+3 weeks and scanned at 38 weeks. GA, gestational age

• 

  Fig. 3 Summary diagram comparing gray matter sites with a significantly higher incidence (percentages) of neuronal loss (A) and gliosis (B) in PVL (left of panel) and DWMG (right of panel) cases. Gliosis of the cerebral and cerebellar white matter, basis pontis, brainstem tegmentum and inferior olives is depicted by small red dots, and focal, periventricular necrosis in the cerebral white matter (PVL) is denoted by a large red periventricular circle.(From Pierson CR, Folkerth RD, et al.14)

• 

  Fig. 4 Topiramate protects against hypoxic-ischemic white matter injury in vivo. (A) Hematoxylin and eosin staining of a coronal brain section from a pup killed at P11 after UCL (unilateral carotid ligation)-hypoxia at P7, demonstrating ipsilateral white matter injury with relative sparing of the overlying cortex. Inset demonstrates regions shown in C-F. B, Dose-response to topiramate in vivo, demonstrating attenuation of MBP injury at P11 with systemic topiramate treatment after hypoxia-ischemia at P7. C, D, Loss of MBP is seen in the P11 pup ipsilateral to a carotid ligation (C), after UCL-hypoxia at P7, and compared with the contralateral side (D). Systemic treatment post-insult with topiramate (30 mg/kg) attenuates this injury in a littermate pup, ipsilateral (E) and contralateral (F). (From Follett PL, Deng W, et al.38)

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