TY - JOUR
T1 - Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury
AU - Mannix, Rebekah
AU - Berglass, Jacqueline
AU - Berkner, Justin
AU - Moleus, Philipp E.
AU - Qiu, Jianhua
AU - Ews, Nick Andr
AU - Gunner, Georgia
AU - Berglass, Laura
AU - Jantzie, Lauren L.
AU - Robinson, Shenandoah
AU - Meehan, William P.
N1 - Publisher Copyright:
©AANS, 2014.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Object. With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. Methods. The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Results. Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. Conclusions. The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.
AB - Object. With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. Methods. The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Results. Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. Conclusions. The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.
KW - Behavior
KW - Closed head injury
KW - Concussion
KW - Gliosis
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85005915317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85005915317&partnerID=8YFLogxK
U2 - 10.3171/2014.7.JNS14272
DO - 10.3171/2014.7.JNS14272
M3 - Article
C2 - 25267088
AN - SCOPUS:85005915317
SN - 0022-3085
VL - 121
SP - 1342
EP - 1350
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 6
ER -