title: Inhaled nitric oxide improves short term memory and reduces the inflammatory reaction in a mouse model of mild traumatic brain injury.
abstract: Although the mechanisms underlying mild traumatic brain injury (mTBI) are becoming well understood, treatment options are still limited. In the present study, mTBI was induced by a weight drop model to produce a closed head injury to mice and the effect of inhaled nitric oxide (INO) was evaluated by a short term memory task (object recognition task) and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and CD45 for the detection of reactive astrocytes and microglia. Results showed that mTBI model did not produce brain edema, skull fracture or sensorimotor coordination dysfunctions. Mice did however exhibit a significant deficit in short term memory (STM) and strong inflammatory reaction in the ipsilateral cortex and hippocampus compared to sham-injured controls 24h after mTBI. Additional groups of untreated mice tested 3 and 7 days later, demonstrated that recognition memory had recovered to normal levels by Day 3. Mice treated with 10ppm INO for 4 or 8h, beginning immediately after TBI demonstrated significantly improved STM at 24h when compared with room air controls (p<0.05). Whereas mice treated with 10ppm INO for 24h showed no improvement in STM. Mice treated with INO 10ppm for 8h exhibited significantly reduced microglia and astrocyte activation compared with room air controls. These data demonstrate that mTBI produces a disruption of STM which is evident 24h after injury and persists for 2-3 days. Treatment with low concentration or short durations of INO prevents this memory loss and also attenuates the inflammatory response. These findings may have relevance for the treatment of patients diagnosed with concussion.
authors.affiliation: Department of Neurology, Huanhu Hospital, Tianjin, China; Laboratory of Behavioral Neurology, Department of Neurology, New York University, School of Medicine, USA. ping.liu@nyumc.org
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Quartermain
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001924:Brain Concussion / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000008:administration & dosage*
chemical_list: D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; D009569:Nitric Oxide; D017493:Leukocyte Common Antigens