title: Restoring GM1 ganglioside expression ameliorates axonal outgrowth inhibition and cognitive impairments induced by blast traumatic brain injury.
abstract: Blast induced traumatic brain injury (B-TBI) may cause various degrees of cognitive and behavioral disturbances but the exact brain pathophysiology involved is poorly understood. It was previously suggested that ganglioside alteration on the axon surface as well as axonal regenerating inhibitors (ARIs) such as myelin associated glycoprotein (MAG) were involved in axonal outgrowth inhibition (AOI), leading to brain damage. GM1 ganglioside content in the brain was significantly reduced while GD1 ganglioside was not affected. The axonal regeneration was also reduced as seen by the phosphorylated NF-H expression. Moreover, B-TBI induced a significant elevation in MAG expression in the brains of the injured mice. The blast injured mice exhibited a significant decline in spatial memory as seen by the Y-maze test. In addition, the injured mice showed pronounced damage to the visual memory (as evaluated by the Novel object recognition test). A single low dose of GM1 (2 mg/kg; IP), shortly after the injury, prevented both the cognitive and the cellular changes in the brains of the injured mice. These results enlighten part of the complicated mechanism that underlies the damage induced by B-TBI and may also suggest a potential new treatment strategy for brain injuries.
authors.affiliation: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978,Israel.
authors.forename: Vardit
authors.initials: V
authors.lastname: Rubovitch
authors.affiliation: Sackler cellular &molecular imaging center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Zilberstein
authors.affiliation: Department of Neurology, The J. Sagol Neuroscience Center, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel.|Department of Neurology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.|Department of Psychiatry, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 64239, Israel.|Department of Psychiatry, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shaul
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978,Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Chaim G
authors.initials: CG
authors.lastname: Pick
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000188:drug therapy; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D005107:Explosions; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D009186:Myelin Sheath / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000199:Actins; D015415:Biomarkers; D005732:Gangliosides; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; C051774:neurofilament protein H; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside