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Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice.

The Journal of comparative neurology | 2019

Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8-10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.

Pubmed ID: 30499129 RIS Download

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HMGB1 antibody - ChIP Grade (antibody)

RRID:AB_444360

This polyclonal targets HMGB1 antibody - ChIP Grade

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beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

Goat polyclonal Secondary Antibody to Rabbit IgG - H&L (HRP) (antibody)

RRID:AB_10679369

This polyclonal targets Goat polyclonal Secondary to Rabbit IgG - H&L (HRP)

View all literature mentions

Iba1 antibody (antibody)

RRID:AB_2224402

This polyclonal targets AIF1

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

GAPDH (I-19) (antibody)

RRID:AB_783595

This polyclonal targets GAPDH

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CD68 antibody [ED1] (antibody)

RRID:AB_1141557

This monoclonal targets CD68 antibody [ED1]

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Polyclonal Rabbit Anti-Goat Immunoglobulins/HRP (antibody)

RRID:AB_2617143

This polyclonal targets Goat immunoglobulins of all classes

View all literature mentions

Polyclonal Rabbit Anti-Goat Immunoglobulins/HRP (antibody)

RRID:AB_2617143

This polyclonal targets Goat immunoglobulins of all classes

View all literature mentions

GAPDH (I-19) (antibody)

RRID:AB_783595

This polyclonal targets GAPDH

View all literature mentions

Goat polyclonal Secondary Antibody to Rabbit IgG - H&L (HRP) (antibody)

RRID:AB_10679369

This polyclonal targets Goat polyclonal Secondary to Rabbit IgG - H&L (HRP)

View all literature mentions

CD68 antibody [ED1] (antibody)

RRID:AB_1141557

This monoclonal targets CD68 antibody [ED1]

View all literature mentions

beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

HMGB1 antibody - ChIP Grade (antibody)

RRID:AB_444360

This polyclonal targets HMGB1 antibody - ChIP Grade

View all literature mentions

beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

Iba1 antibody (antibody)

RRID:AB_2224402

This polyclonal targets AIF1

View all literature mentions

HMGB1 antibody - ChIP Grade (antibody)

RRID:AB_444360

This polyclonal targets HMGB1 antibody - ChIP Grade

View all literature mentions

Iba1 antibody (antibody)

RRID:AB_2224402

This polyclonal targets AIF1

View all literature mentions

Iba1 antibody (antibody)

RRID:AB_2224402

This polyclonal targets AIF1

View all literature mentions

Anti-NeuN (antibody)

RRID:AB_2298772

This monoclonal targets NeuN

View all literature mentions

Polyclonal Rabbit Anti-Goat Immunoglobulins/HRP (antibody)

RRID:AB_2617143

This polyclonal targets Goat immunoglobulins of all classes

View all literature mentions

Goat polyclonal Secondary Antibody to Rabbit IgG - H&L (HRP) (antibody)

RRID:AB_10679369

This polyclonal targets Goat polyclonal Secondary to Rabbit IgG - H&L (HRP)

View all literature mentions

beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

GAPDH (I-19) (antibody)

RRID:AB_783595

This polyclonal targets GAPDH

View all literature mentions

CD68 antibody [ED1] (antibody)

RRID:AB_1141557

This monoclonal targets CD68 antibody [ED1]

View all literature mentions

HMGB1 antibody - ChIP Grade (antibody)

RRID:AB_444360

This polyclonal targets HMGB1 antibody - ChIP Grade

View all literature mentions