title: Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury.
abstract: Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated, mitochondrial, and endoplasmic reticulum stress pathways. Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury, and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra. Here, we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12, caspase-3 and the endoplasmic reticulum stress marker 78 kDa glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours. Furthermore, numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury. These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra, and may play an important role in the pathophysiology of secondary brain injury.
authors.affiliation: Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Guo-Zhu
authors.identifier: 0000-0001-6380-8793
authors.initials: GZ
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong Province, China.
authors.forename: Fen-Fei
authors.initials: FF
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Zong-Mao
authors.initials: ZM
authors.lastname: Zhao
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Yong-Chang
authors.initials: YC
authors.lastname: He
keywords: apoptosis; caspase-12; caspase-3; endoplasmic reticulum stress; nerve regeneration; neural regeneration; traumatic brain injury; traumatic penumbra