Hypoxic-ischemic encephalopathy in the term infant

Abstract

Hypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last 2 decades, and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this article the authors discuss several molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets.

Figure 1

Diffusion-Weighted Imaging (DWI) and T2-weighted imaging in a neonate with HIE 24 hours (A) and 3 days (B) after birth. DWI at 24h shows hyperintensities in the bilateral thalami and posterior limbs of the internal capsule (left greater than right), which are not recognized on T2-weighted images at the same levels. Repeat DWI at 3 days of life demonstrates diffuse hyperintensities in the bilateral basal ganglia and thalami as well as the internal capsule. Gyral enhancement consistent with cortical injury is observed in multiple areas, and is most prominent in the bilateral medial temporal and occipital lobes and less evident in the parasagittal frontal and parietal lobes. These changes are present but much less prominent on T2-weighted images at the same levels. (Modified from Takeoka M. et al, Pediatr Neurol 2002;26:274-281.)

Figure 2

Proton Magnetic Resonance Spectroscopy in newborn infants after HI showing Choline (Cho), Creatine (Cr), N-Acetyl-Aspartate (NAA), Lactate (Lac). A) Spectra of a healthy newborn showing normal NAA to Creatine ratio, and minimum lactate double-peak. B) Newborn with moderate HIE, showing normal NAA, but elevated lactate double-peak. C) Newborn with severe HIE showing low NAA and markedly increased lactate. (Modified from Cheong JLY et al. AJNR 2006;27:1546-1554.)

Figure 3

Necrosis-Apoptosis spectrum in neurons after HI in the neonatal rat. Nuclear changes in degenerating cells in cortex 48 hr after HI. Light microscopic photographs of 1 mm, Nissl-stained sections (A–C) and electron micrographs (A1–C1) are shown. An intermediate type of degenerating neurons was found, hybrid cells (arrow, A, A1) with large, chromatin clumps in the nucleus that were similar in size to those found in cells undergoing apoptosis but that were more irregular in shape. Typical necrotic neurons had smaller clumps of irregularly shaped, condensed chromatin (asterisk in A; arrows in B, B1). Necrotic neurons, which had a relatively homogeneous nucleus with a few irregular chromatin clumps and condensed granular cytoplasm (C, C1) and were typically found in adult ischemic models, were rarely identified in this model. Scale bars: A–C, 10 mm; A1, C1, 2 mm; B1, 1 mm. (Reprinted from J Neuroscience, November 1, 2000, 20(21):7994–8004)

Figure 4

Cell death pathways involved in hypoxic-ischemic brain injury