Effects of a Subanesthetic Ketamine Infusion on Inflammatory and Behavioral Outcomes after Closed Head Injury in Rats

被引:4
作者
Spencer, Haley F. [1 ,2 ]
Boese, Martin [3 ]
Berman, Rina Y. [2 ]
Radford, Kennett D. [3 ]
Choi, Kwang H. [1 ,2 ,3 ,4 ]
机构
[1] Uniformed Serv Univ Hlth Sci, Program Neurosci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
[2] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
[3] Uniformed Serv Univ Hlth Sci, Daniel K Inouye Grad Sch Nursing, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
[4] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA
来源
BIOENGINEERING-BASEL | 2023年 / 10卷 / 08期
关键词
mild traumatic brain injury; CHIMERA; ketamine; cytokines; axonal damage; rotarod;
D O I
10.3390/bioengineering10080941
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF- alpha, and IL-1 fi levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.
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页数:20
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