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Increased expression and processing of caspase‐12 after traumatic brain injury in rats
Author(s) -
Larner Stephen F.,
Hayes Ronald L.,
McKinsey Deborah M.,
Pike Brian R.,
Wang Kevin K. W.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02141.x
Subject(s) - traumatic brain injury , hippocampus , caspase 3 , apoptosis , endoplasmic reticulum , caspase , cortex (anatomy) , caspase 12 , immunohistochemistry , caspase 9 , medicine , chemistry , biology , endocrinology , microbiology and biotechnology , programmed cell death , neuroscience , biochemistry , psychiatry
Abstract Traumatic brain injury (TBI) disrupts tissue homeostasis resulting in pathological apoptotic activation. Recently, caspase‐12 was reported to be induced and activated by the unfolded protein response following excess endoplasmic reticulum (ER) stress. This study examined rat caspase‐12 expression using the controlled cortical impact TBI model. Immunoblots of fractionalized cell lysates found elevated caspase‐12 proform (∼60 kDa) and processed form (∼12 kDa), with peak induction observed within 24 h post‐injury in the cortex (418% and 503%, respectively). Hippocampus caspase‐12 proform induction peaked at 24 h post‐injury (641%), while processed form induction peaked at 6 h (620%). Semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis confirmed elevated caspase‐12 mRNA levels after TBI. Injury severity (1.0, 1.2 or 1.6 mm compression) was associated with increased caspase‐12 mRNA expression, peaking at 5 days in the cortex (657%, 651% and 1259%, respectively) and 6 h in the hippocampus (435%, 451% and 460%, respectively). Immunohistochemical analysis revealed caspase‐12 induction in neurons in both the cortex and hippocampus as well as in astrocytes at the contusion site. This is the first report of increased expression of caspase‐12 following TBI. Our results suggest that the caspase‐12‐mediated ER apoptotic pathway may play a role in rat TBI pathology independent of the receptor‐ or mitochondria‐mediated apoptotic pathways.