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Ketamine Alters Hippocampal Cell Proliferation and Improves Learning in Mice after Traumatic Brain Injury.

Abstract：

WHAT WE ALREADY KNOW ABOUT THIS TOPIC:WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Traumatic brain injury induces cellular proliferation in the hippocampus, which generates new neurons and glial cells during recovery. This process is regulated by N-methyl-D-aspartate-type glutamate receptors, which are inhibited by ketamine. The authors hypothesized that ketamine treatment after traumatic brain injury would reduce hippocampal cell proliferation, leading to worse behavioral outcomes in mice. METHODS:Traumatic brain injury was induced in mice using a controlled cortical impact injury, after which mice (N = 118) received either ketamine or vehicle systemically for 1 week. The authors utilized immunohistochemical assays to evaluate neuronal, astroglial, and microglial cell proliferation and survival 3 days, 2 weeks, and 6 weeks postintervention. The Morris water maze reversal task was used to assess cognitive recovery. RESULTS:Ketamine dramatically increased microglial proliferation in the granule cell layer of the hippocampus 3 days after injury (injury + vehicle, 2,800 ± 2,700 cells/mm, n = 4; injury + ketamine, 11,200 ± 6,600 cells/mm, n = 6; P = 0.012). Ketamine treatment also prevented the production of astrocytes 2 weeks after injury (sham + vehicle, 2,400 ± 3,200 cells/mm, n = 13; injury + vehicle, 10,500 ± 11,300 cells/mm, n = 12; P = 0.013 vs. sham + vehicle; sham + ketamine, 3,500 ± 4,900 cells/mm, n = 14; injury + ketamine, 4,800 ± 3,000 cells/mm, n = 13; P = 0.955 vs. sham + ketamine). Independent of injury, ketamine temporarily reduced neurogenesis (vehicle-exposed, 105,100 ± 66,700, cells/mm, n = 25; ketamine-exposed, 74,300 ± 29,200 cells/mm, n = 27; P = 0.031). Ketamine administration improved performance in the Morris water maze reversal test after injury, but had no effect on performance in sham-treated mice. CONCLUSIONS:Ketamine alters hippocampal cell proliferation after traumatic brain injury. Surprisingly, these changes were associated with improvement in a neurogenesis-related behavioral recall task, suggesting a possible benefit from ketamine administration after traumatic brain injury in mice. Future studies are needed to determine generalizability and mechanism.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Peters AJ,Villasana LE,Schnell E

doi

10.1097/ALN.0000000000002197

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

278-295

issue

eissn

0003-3022

issn

1528-1175

journal_volume

129

pub_type

杂志文章

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Ketamine Alters Hippocampal Cell Proliferation and Improves Learning in Mice after Traumatic Brain Injury.