Ultrastructural brain abnormalities and associated behavioral changes in mice after low-intensity blast exposure

作者：Song Hailong; Konan Landry M; Cui Jiankun; Johnson Catherine E; Langenderfer Martin; Grant DeAna; Ndam Tina; Simonyi Agnes; White Tommi; Demirci Utkan; Mott David R; Schwer Doug; Hubler Graham K; Cernak Ibolja; DePalma Ralph G; Gu Zezong^*

来源：Behavioural Brain Research, 2018, 347: 148-157.

DOI：10.1016/j.bbr.2018.03.007

• Blast-induced TBI
• Blast wave
• Behavior
• Neuropathology
• Ultrastructural abnormalities

Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI x ms and a sharp rising time of 9 x 10(-3) ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment.

• 出版日期2018-7-16