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


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


CONCLUSIONS
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.
Department of Basic Science, Columbia University, New York, NY, USA.
Tim
T
Lekic
Department of Basic Science, Columbia University, New York, NY, USA.
Damon
D
Klebe
Department of Pediatrics, Columbia University, New York, NY, USA.
Pilar
P
Pichon
Department of Basic Science, Columbia University, New York, NY, USA.
Katarina
K
Brankov
Department of Pediatric Neurology, Columbia University, New York, NY, USA.
Sally
S
Sultan
Department of Basic Science, Columbia University, New York, NY, USA.
Devin
D
McBride
Department of Neonatology, Columbia University, New York, NY, USA.
Darlene
D
Casel
Department of Neurology, Columbia University, New York, NY, USA.
Alhamza
A
Al-Bayati
Department of Basic Science, Columbia University, New York, NY, USA.
Yan
Y
Ding
Department of Basic Science, Columbia University, New York, NY, USA.
Jiping
J
Tang
Department of Basic Science, Columbia University, New York, NY, USA.|[Department of Anesthesiology, School of Medicine, Loma Linda, CA, USA.
John H
JH
Zhang
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007502:Iron Chelating Agents / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D007502:Iron Chelating Agents
Animal model; drug discovery; experimental; hydrocephalus; neurological dysfunction; translational research