Benefits of hypothermia in neonatal arterial ischemic strokes: A preclinical study

Int J Dev Neurosci. 2020 Jun;80(4):257-266. doi: 10.1002/jdn.10022. Epub 2020 Mar 24.

Abstract

Background: There is currently no targeted treatment available for neonatal arterial ischemic strokes (NAIS). Epidemiological studies demonstrated that perinatal infection/inflammation, peripartum hypoxia, and occlusion of the internal carotid tree are the main determinants of NAIS. The well-established benefit of therapeutic hypothermia (HT) in neonatal encephalopathy due to diffuse hypoxia-ischemia provides a rationale for the potential use of HT as a neuroprotective strategy in NAIS.

Methods: We used a rat model to reproduce the most prevalent human physiopathological scenario of NAIS. The neuroprotective effect of HT was measured by morphometric magnetic resonance imaging, [18 F] fluorodeoxyglucose (FDG) metabolic activity by positron emission tomography/computed tomography, and behavioral tests.

Results: HT (a) prevented the occurrence of 44% of NAIS, (b) reduced the volume of strokes by 37%, (c) enhanced [18 F] FDG metabolic activity within the territory of the occluded carotid artery, and (d) improved motor behavior. Both morphometric and metabolic techniques showed consistently that HT provided a neuroprotective effect located in the motor cortex, hippocampus, and caudate-putamen.

Conclusion: Through combining anatomical, metabolic imaging, and behavioral studies, our study provides evidence of neuroprotective effects of HT in NAIS. These results are potentially translational to human NAIS.

Keywords: HT; MRI; NAIS; PET/CT; inflammation.

MeSH terms

  • Animals
  • Animals, Newborn
  • Caudate Nucleus / diagnostic imaging
  • Female
  • Hippocampus / diagnostic imaging
  • Humans
  • Hypothermia, Induced / methods*
  • Hypoxia-Ischemia, Brain / diagnostic imaging
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant, Newborn
  • Ischemic Stroke / diagnostic imaging
  • Ischemic Stroke / prevention & control*
  • Magnetic Resonance Imaging
  • Male
  • Motor Activity
  • Motor Cortex / diagnostic imaging
  • Neuroprotection*
  • Positron Emission Tomography Computed Tomography
  • Putamen / diagnostic imaging
  • Rats
  • Rats, Inbred Lew