title: Cytoskeletal protein α-II spectrin degradation in the brain of repeated blast exposed mice.
abstract: Repeated blast exposures commonly induce traumatic brain injury (TBI) characterized by diffuse axonal injury (DAI). We hypothesized that degradation of cytoskeletal proteins in the brain can lead to DAI, and evaluated α-II spectrin degradation in the pathophysiology of blast-induced TBI using the tightly-coupled three repetitive blast exposure mice model with a 1-30 min window in between exposures. Degradation of α-II spectrin and the expression profiles of caspase-3 and calpain-2, the major enzymes involved in the degradation were analyzed in the frontal cortex and cerebellum using Western blotting with specific antibodies. DAI at different brain regions was evaluated by neuropathology with silver staining. Repeated blast exposures resulted in significant increases in the α-II spectrin degradation products in the frontal cortex and cerebellum compared to sham controls. Expression of active caspase-3, which degrades α-II spectrin, showed significant increase in the frontal cortex after blast exposure at all the time points studied, while cerebellum showed an acute increase which was normalized over time. The expression of another α-II spectrin degrading enzyme, calpain-2, showed a rapid increase in the frontal cortex after blast exposure and it was significantly higher in the cerebellum at later time points. Neuropathological analysis showed significant levels of DAI at the frontal cortex and cerebellum at multiple time points after repeated blast injury. In summary, repeated blast exposure results in specific degradation of α-II spectrin in the brain along with differential expression of caspase-3/calpain-2 suggesting cytoskeletal breakdown as a possible contributor of DAI after repeated blast exposure.
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: m.valiyaveettil@us.army.mil.
authors.forename: Manoj
authors.initials: M
authors.lastname: Valiyaveettil
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Yonas A
authors.initials: YA
authors.lastname: Alamneh
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Peethambaran
authors.initials: P
authors.lastname: Arun
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Oguntayo
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Long
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address: madhunambiar1@gmail.com.
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001753:Blast Injuries / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051379:Mice; D013049:Spectrin / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D013049:Spectrin; D002154:Calpain; D053148:Caspase 3; C570925:Capn2 protein, mouse
keywords: Calpain-2; Caspase-3; Cytoskeleton; Diffuse axonal injury; Repeated blast exposure; Traumatic brain injury; α-II spectrin