Basic science; metallothionein I and II attenuate the thalamic microglial response following traumatic axotomy in the immature brain.
The clinical manifestations of inflicted traumatic brain injury in infancy most commonly result from intracranial hemorrhage, axonal stretch and disruption, and cerebral edema. Often hypoxia ischemia is superimposed, leading to early forebrain and later thalamic neurodegeneration. Such acute and delayed cellular injury activates microglia in the CNS. Although activated microglia provide important benefits in response to injury, microglial release of reactive oxygen species can be harmful to axotomized neurons. We have previously shown that the antioxidants metallothionein I and II (MT I & II) promote geniculocortical neuronal survival after visual cortex lesioning. The purpose of this investigation was to determine the influence of MT I & II on the density and rate of thalamic microglial activation and accumulation following in vivo axotomy. We ablated the visual cortex of 10-day-old and adult MT I & II knock out (MT(-/-)) and wild-type mice and then determined the density of microglia in the dorsal lateral geniculate nucleus (dLGN) over time. Compared to the wild-type strain, microglial activation occurred earlier in both young and adult MT(-/-) mice. Similarly, microglial density was significantly greater in young MT(-/-) mice 30, 36, and 48 hours after injury, and 3, 4, and 5 days after injury in MT(-/-) adults. In both younger and older mice, time and MT I & II deficiency each contributed significantly to greater microglial density. Only in younger mice did MT I & II expression significantly slow the rate (density x time) of microglial accumulation. These results suggest that augmentation of MT I & II expression may provide therapeutic benefits to infants with inflicted brain injury.
Potter
Emily G
EG
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Cheng
Ying
Y
Knight
Jay Brandon
JB
Gordish-Dressman
Heather
H
Natale
JoAnne E
JE
D000375:Aging / Q000502:physiology; D000818:Animals; D019771:Axotomy; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D016923:Cell Death; D007150:Immunohistochemistry; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000502:physiology; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology*; D014793:Visual Cortex / Q000473:pathology
D008668:Metallothionein