Long-term increase in sensitivity to ketamine's behavioral effects in mice exposed to mild blast induced traumatic brain injury.
Long-term increase in sensitivity to ketamine's behavioral effects in mice exposed to mild blast induced traumatic brain injury.
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DOI：
10.1016/j.expneurol.2021.113963
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发表时间：
2022-04
影响因子：
5.3
通讯作者：
Lucki I
中科院分区：
文献类型：
--
作者：
Browne CA;Wulf HA;Jacobson ML;Oyola MG;Wu TJ;Lucki I
近50%的患者在轻度创伤性脑损伤（TBI）后出现神经行为缺陷，并可能持续数月。氯胺酮常被用作麻醉剂、镇痛药和治疗持续性精神并发症。虽然氯胺酮可能对有TBI病史的患者产生有益作用，但对其损害作用的不同敏感性可能使氯胺酮在TBI患者中的治疗使用不安全。本系列研究检查了暴露于轻度单次爆炸超压（mbTBI）的雄性C57BL/6J小鼠在受伤后不同时间对氯胺酮敏感性改变的迹象。在损伤后7-16天，以及损伤后35-43天，在mbTBI和假手术动物中，腹腔注射生理盐水或R， s -氯胺酮15分钟后，检测运动障碍（步态改变）、感觉运动门控减弱（脉冲前抑制减弱）、工作记忆受损（抑制性回避减弱）。分别于给药后第28天和第74天进行强迫游泳试验和糖偏好试验。mbTBI小鼠的动态步态稳定性在损伤后第7天和第35天受到损害，氯胺酮给药后进一步恶化。在损伤后第14天和第42天，mbTBI对脉冲前抑制作用明显降低，氯胺酮进一步降低。氯胺酮相关的记忆损伤在mbTBI动物休克后1小时、24小时和28天有明显选择性（损伤后15/16/43天进行测试）。氯胺酮选择性地降低mbTBI动物FST的不动评分（第28天），并逆转mbTBI诱导的糖消耗减少（第74天）。这些结果表明，在创伤性脑损伤后的较长时间内，小鼠对氯胺酮的敏感性增加。结果表明氯胺酮可能对治疗创伤性脑损伤后出现的神经精神并发症有效，但在临床实践中使用氯胺酮时要谨慎，因为这类患者对其副作用更敏感。
Neurobehavioral deficits emerge in nearly 50% of patients following a mild traumatic brain injury (TBI) and may persist for months. Ketamine is used frequently as an anesthetic, analgesic and for management of persistent psychiatric complications. Although ketamine may produce beneficial effects in patients with a history of TBI, differential sensitivity to its impairing effects could make the therapeutic use of ketamine in TBI patients unsafe. This series of studies examined male C57BL/6J mice exposed to a mild single blast overpressure (mbTBI) for indications of altered sensitivity to ketamine at varying times after injury. Dystaxia (altered gait), diminished sensorimotor gating (reduced prepulse inhibition) impaired working memory (step-down inhibitory avoidance) were examined in mbTBI and sham animals 15 minutes following intraperitoneal injections of saline or R,S-ketamine hydrochloride, from day 7–16 post injury and again from day 35–43 post injury. Behavioral performance in the forced swim test and sucrose preference test were evaluated on day 28 and day 74 post injury respectively, 24 hours following drug administration. Dynamic gait stability was compromised in mbTBI mice on day 7 and 35 post injury and further exacerbated following ketamine administration. On day 14 and 42 post injury, prepulse inhibition was robustly decreased by mbTBI, which ketamine further reduced. Ketamine-associated memory impairment was apparent selectively in mbTBI animals 1 h, 24 h and day 28 post shock (tested on day 15/16/43 post injury). Ketamine selectively reduced immobility scores in the FST in mbTBI animals (day 28) and reversed mbTBI induced decreases in sucrose consumption (Day 74). These results demonstrate increased sensitivity to ketamine in mice when tested for extended periods after TBI. The results suggest that ketamine may be effective for treating neuropsychiatric complications that emerge after TBI but urge caution when used in clinical practice for enhanced sensitivity to its side effects in this patient population.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
11
作者：
Fava M;Freeman MP;Flynn M;Judge H;Hoeppner BB;Cusin C;Ionescu DF;Mathew SJ;Chang LC;Iosifescu DV;Murrough J;Debattista C;Schatzberg AF;Trivedi MH;Jha MK;Sanacora G;Wilkinson ST;Papakostas GI
通讯作者：
Papakostas GI
影响因子：
3.4
作者：
Hartberg, John;Garrett-Walcott, Simone;De Gioannis, Angelo
通讯作者：
De Gioannis, Angelo
影响因子：
3.4
作者：
Jacobson ML;Wulf HA;Browne CA;Lucki I
通讯作者：
Lucki I
DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr