Aligning Animal Models of Clinical Germinal Matrix Hemorrhage, From Basic Correlation to Therapeutic Approach

Curr Drug Targets. 2017;18(12):1316-1328. doi: 10.2174/1389450117666160615100538.

Abstract

Background: Germinal matrix hemorrhage is a leading cause of mortality and morbidity from prematurity. This brain region is vulnerable to bleeding and re-bleeding within the first 72 hours of preterm life. Cerebroventricular expansion of blood products contributes to the mechanisms of brain injury. Consequences include lifelong hydrocephalus, cerebral palsy, and intellectual disability. Unfortunately little is known about the therapeutic needs of this patient population.

Objectives: This review discusses the mechanisms of germinal matrix hemorrhage, the animal models utilized, and the potential therapeutic targets.

Conclusion: Potential therapeutic approaches identified in pre-clinical investigations include corticosteroid therapy, iron chelator administration, and transforming growth factor-β pathway modulation, which all warrant further investigation. Thus, effective preclinical modeling is essential for elucidating and evaluating novel therapeutic approaches, ahead of clinical consideration.

Keywords: Animal model; drug discovery; experimental; hydrocephalus; neurological dysfunction; translational research.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Animals, Newborn
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology*
  • Disease Models, Animal*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Iron Chelating Agents / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Iron Chelating Agents