| 제목 |
SP-8356 alleviates the deterioration of sensory-motor function due to repetitive concussive TBI |
| 소속 |
Korea University College of Medicine, Department of Neuroscience1, Korea University College of Medicine, Institute of Inflammation Control2, Korea University College of Medicine, Department of Physical Medicine and Rehabilitation3 |
| 저자 |
Sekwang Lee1,3*, Won-Ki Kim1,2† |
Background & Purpose
Mild traumatic brain injury (mTBI) is one of the major concerns in the US public healthcare area and accounts for the majority of all TBI. Clinical studies have shown that increased susceptibility to additional mTBI can lead to cumulative effects of further injury. Recent drug development strategies target potentially modifiable secondary pathways that can be treated and are generally associated with promoting neuroprotection or inhibiting neurotoxins. We evaluated the effect of SP-8356, an anti-inflammatory synthetic verbenone derivative, on its regulation of repetitive concussive TBI (rcTBI)-evoked sensory-motor deficits.
Method
C57BL/6 mice were anesthetized and placed on a floor made of Kimwipe. At a height of 1.7 meters, 50 g of metal weight was dropped vertically into the pipe to induce weight-drop injury in the mouse's head. The impact resulted in free movement of the head and body as the mice penetrate the Kimwipe upon impact and free fall onto a padded floor below. SP-8356 (50 mg/kg) or vehicle (normal saline) was intraperitoneally administered at 2, 7 and 24 h after TBI. Weight drop injuries were performed twice at 24-h intervals. The Rotarod test was performed 5 times before the injury for training. Post-injury assessments were performed 24 h after the first injury (day 0, before the second injury) and further at one and two days after the second injury.
Results
The fall latencies in RRT tended to decrease after two consecutive TBIs. However, at the day after the second injury SP-8356 significantly reversed the decrease of fall latency in RRT compared to the vehicle group (P = 0.025). The effect of SP-8356 on the expression of inflammatory cytokines, astrogliosis, and microglial activation in mouse brain damaged after the repetitive concussion will be further discussed in the presentation.
Conclusion
SP-8356 alleviated the deterioration of the sensory-motor function due to two repetitive concussive TBIs. SP-8356 may be a potential therapeutic agent for repetitive concussive TBI by playing a role in acute physiological recovery and reducing the potential for cumulative damage in further injury.
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