Timing of appearance of late oligodendrocyte progenitors coincides with enhanced susceptibility of preterm rabbit cerebral white matter to hypoxia-ischemia.
Emerging evidence supports that premature infants are susceptible to both cerebral white and gray matter injury. In a fetal rabbit model of placental insufficiency, preterm rabbits at embryonic day 22 (E22) exhibited histologic evidence of gray matter injury but minimal white matter injury after global hypoxia-ischemia (H-I). We hypothesized that the dissociation between susceptibility to gray and white matter injury at E22 was related to the timing of appearance of late oligodendrocyte progenitors (preOLs) that are particularly vulnerable in preterm human white matter lesions. During normal rabbit oligodendrocyte (OL) lineage progression, early OL progenitors predominated at E22. PreOL density increased between E24 and E25 in major forebrain white matter tracts. After H-I at E22 and E25, we observed a similar magnitude of cerebral H-I, assessed by cortical microvascular blood flow, and gray matter injury, assessed by caspase activation. However, the increased preOL density at E25 was accompanied by a significant increase in acute white matter injury after H-I that coincided with enhanced preOL degeneration. At E29, significant white matter atrophy developed after H-I at E25 but not E22. Thus, the timing of appearance of preOLs coincided with onset of a developmental window of enhanced white but not gray matter susceptibility to H-I.
Buser
Joshua R
JR
Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Segovia
Kristen N
KN
Dean
Justin M
JM
Nelson
Kerst
K
Beardsley
Douglas
D
Gong
Xi
X
Luo
Ning Ling
NL
Ren
Jennifer
J
Wan
Ying
Y
Riddle
Art
A
McClure
Melissa M
MM
Ji
Xinhai
X
Derrick
Matthew
M
Hohimer
A Roger
AR
Back
Stephen A
SA
Tan
Sidhartha
S
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000196:embryology; D053148:Caspase 3 / Q000378:metabolism; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005333:Fetus / Q000473:pathology / Q000503:physiopathology; D005865:Gestational Age; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D053148:Caspase 3