Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion.
Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion.
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创伤性脑损伤后巨噬细胞迁移抑制厂（MIF）的拮抗作用可改善星形细胞增多症和周围淋巴细胞的激活和扩张。
DOI：
10.3390/ijms21207448
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发表时间：
2020-10-09
影响因子：
5.6
通讯作者：
Shapiro LA
中科院分区：
文献类型：
--
作者：
Newell-Rogers MK;Rogers SK;Tobin RP;Mukherjee S;Shapiro LA
创伤性脑损伤（TBI）在高达15-20%的症状性癫痫和高达5%的所有癫痫中先于癫痫发作。获得性癫痫（包括创伤后癫痫（PTE））的治疗存在临床挑战，包括对抗癫痫治疗的频繁抵抗。考虑到每年有超过160万美国人患有TBI，PTE是一个紧迫的临床问题。神经炎症被认为在包括PTE在内的许多创伤后综合征中起主要的致病作用。越来越多的证据表明，神经炎症促进并可能有助于癫痫发作的诱导和传播。炎症细胞因子巨噬细胞移动抑制因子（MIF）在TBI后升高，并且MIF的较高水平与更差的创伤后结果相关。MIF最近被证明可以直接改变海马CA 1区锥体神经元的放电动力学，海马CA 1区锥体神经元是许多类型癫痫发作的关键结构。我们推测，TBI后拮抗MIF将具有抗炎、抗神经炎症和神经保护作用。结果表明，在TBI后30分钟给予MIF拮抗剂ISO 1防止星形细胞增多，但在病变周围皮质中没有神经保护作用。结果还表明，ISO 1抑制TBI诱导的肠道中γδT细胞的增加，以及B细胞浸润到脑中的百分比。ISO 1处理也增加了脾脏中的B细胞群。这些研究结果进行了讨论，着眼于其治疗潜力的创伤后综合征，包括PTE。
Traumatic brain injury (TBI) precedes the onset of epilepsy in up to 15–20% of symptomatic epilepsies and up to 5% of all epilepsy. Treatment of acquired epilepsies, including post-traumatic epilepsy (PTE), presents clinical challenges, including frequent resistance to anti-epileptic therapies. Considering that over 1.6 million Americans present with a TBI each year, PTE is an urgent clinical problem. Neuroinflammation is thought to play a major causative role in many of the post-traumatic syndromes, including PTE. Increasing evidence suggests that neuroinflammation facilitates and potentially contributes to seizure induction and propagation. The inflammatory cytokine, macrophage migration inhibitory factor (MIF), is elevated after TBI and higher levels of MIF correlate with worse post-traumatic outcomes. MIF was recently demonstrated to directly alter the firing dynamics of CA1 pyramidal neurons in the hippocampus, a structure critically involved in many types of seizures. We hypothesized that antagonizing MIF after TBI would be anti-inflammatory, anti-neuroinflammatory and neuroprotective. The results show that administering the MIF antagonist ISO1 at 30 min after TBI prevented astrocytosis but was not neuroprotective in the peri-lesion cortex. The results also show that ISO1 inhibited the TBI-induced increase in γδT cells in the gut, and the percent of B cells infiltrating into the brain. The ISO1 treatment also increased this population of B cells in the spleen. These findings are discussed with an eye towards their therapeutic potential for post-traumatic syndromes, including PTE.
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影响因子：
7.4
作者：
Bekhbat M;Rowson SA;Neigh GN
通讯作者：
Neigh GN
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
DOI：
10.1073/pnas.56.1.72
发表时间：
1966-01-01
影响因子：
11.1
作者：
DAVID, JR
通讯作者：
DAVID, JR
影响因子：
5.3
作者：
Bertani, Ilaria;Iori, Valentina;Chiesa, Roberto
通讯作者：
Chiesa, Roberto
DOI：
10.7759/cureus.744
发表时间：
2016-08-22
期刊：
Cureus
影响因子：
--
作者：
Larkin M;Meyer RM;Szuflita NS;Severson MA;Levine ZT
通讯作者：
Levine ZT