Minocycline fails to treat chronic traumatic brain injury-induced impulsivity and attention deficits.
Minocycline fails to treat chronic traumatic brain injury-induced impulsivity and attention deficits.
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DOI：
10.1016/j.expneurol.2021.113924
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发表时间：
2022-03
影响因子：
5.3
通讯作者：
Vonder Haar, C.
中科院分区：
文献类型：
--
作者：
Pechacek, K. M.;Reck, A. M.;Frankot, M. A.;Vonder Haar, C.
创伤性脑损伤（TBI）影响全球数百万人，并可引起持久的精神症状。慢性神经炎症是损伤后病理的特征，也与精神疾病如多动症和双相情感障碍有关。因此，目前的研究试图确定是否可以使用米诺环素（一种具有抗炎特性的抗生素）治疗脑外伤引起的冲动和注意力不集中。大鼠接受了五项连续反应时间任务（5CSRT）的训练，这是一种测量运动冲动和注意力的方法。在5CSRT上行为稳定后，大鼠接受双侧额叶脑损伤或假手术。在早期（损伤后1小时）或慢性（损伤后9周）时间点给予米诺环素。米诺环素每12小时给药一次，共5天（45 mg/kg, ig）。5CSRT恢复一周后再次进行行为测试，持续12周，然后经心灌流大鼠。冲动和注意力不集中在脑外伤后都显著增加。米诺环素在早期和晚期均无治疗效果。脑外伤大鼠病变体积增大，但二甲胺四环素未减弱病变大小。此外，通过IBA-1+细胞测量的小胶质细胞计数仅在TBI后急剧增加，二甲胺四环素对TBI大鼠的小胶质细胞数量没有差异。尽管如此，二甲胺四环素对肠道微生物群有明显的影响。基于这项研究的结果，米诺环素对损伤后精神类症状的疗效可能有限。
Traumatic brain injury (TBI) impacts millions worldwide and can cause lasting psychiatric symptoms. Chronic neuroinflammation is a characteristic of post-injury pathology and is also associated with psychiatric conditions such as ADHD and bipolar disorder. Therefore, the current study sought to determine whether TBI-induced impulsivity and inattention could be treated using minocycline, an antibiotic with anti-inflammatory properties. Rats were trained on the five-choice serial reaction time task (5CSRT), a measure of motor impulsivity and attention. After behavior was stable on the 5CSRT, rats received either a bilateral frontal TBI or sham procedure. Minocycline was given at either an early (1 h post-injury) or chronic (9 weeks post-injury) timepoint. Minocycline was delivered every 12 h for 5 days (45 mg/kg, i.p.). Behavioral testing on the 5CSRT began again after one week of recovery and continued for 12 more weeks, then rats were transcardially perfused. Impulsivity and inattention were both substantially increased following TBI. Minocycline had no therapeutic effects at either the early or late time points. TBI rats had increased lesion volume, but minocycline did not attenuate lesion size. Additionally, microglia count measured by IBA-1+ cells was only increased acutely after TBI, and minocycline did not differentially change the number of microglia in TBI rats. Despite this, minocycline had clear effects on the gut microbiome. Based on the results of this study, minocycline may have limited efficacy for post-injury psychiatric-like symptoms.
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