Table 1.

Comparison of Neonatal Brain Hemorrhage (NBH) Animal Models.

Species	NBH Induction Method	Developmental Ages Comparable to Pre-term Humans	Advantages	Disadvantages
Rodents [29-30, 84, 333- 335, 357]	Injection of autologous blood or collagenase into the periven- tricular region	Newborns comparable to 24-26 week human gestational age, 7 day-old rats comparable to 32 week human gestational age	Availability of knockout strains, well-documented neonatal brain development, germinal matrix in postnatal age, and inexpen- sive	Substantial anatomical and physio- logical differences with humans
Rabbits [380, 384, 407- 414]	Intraperitoneal injection of glycerol to induce intracranial hypotension, sodium bicarbon- ate hyperosmolality, or fu- rosemide diuresis	28 days gestation or 3-4 days before term are most comparable to pre-term humans	Some postnatal brain develop- ment features similar to fetal humans, such as blood vessel immaturity in germinal matrix	Inconsistent and diffuse hemor- rhage development
Pigs [415-424]	Intraventricular autologous blood injection	Studies performed in newborn pigs, not very comparable to humans	Good for studying pathogenesis of brain injury in neonates	Brain is developmentally mature
Sheep [385, 425-431]	Asphyxia with arterial and venous hypertension in exteri- orized sheep fetuses	58 to 85 days gestation compara- ble to 26-30 week preterm hu- mans	Vasculature of germinal layer is similar to humans	Brain is developmentally mature at birth, inconsistent hemorrhage development, sheep fetuses must remain unbilically attached their mothers, and sheep have carotid rete mirables
Cats [432]	hypernatremia induced by intraperitoneal sodium injection	Studies performed in 6+ week old kittens, not very comparable to humans	Well documented neonatal neuronal development	Poor documentation on kitten germinal matrix and hemorrhage sites in prior studies
Dogs [132, 378- 379, 383, 386, 433-450]	Induced hypertension, hypoten- sion, or hypercarbia at 12-48 hours post-birth in beagles, or asphyxiation of beagles at 6 days before term	Substantial germinal matrix layer at term that is comparable to pre- term humans	Large size makes physiological observations easy, many well documented studies related to neonatal brain hemorrhage	Inconsistent hemorrhage develo- pment, limited long-term neurofunc- tional studies, and dog brains contain a carotid rete mirables
Primates [451-456]	Prematurely delivered baboons at 125-days gestation spontane- ously develop hemorrhages	Baboons at 100 days gestation comparable to 24-week human gestation age	Most comparable to human development, spontaneous NBH development	Very expensive