Lack of the Nlrp3 Inflammasome Improves Mice Recovery Following Traumatic Brain Injury.
Lack of the Nlrp3 Inflammasome Improves Mice Recovery Following Traumatic Brain Injury.
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DOI：
10.3389/fphar.2017.00459
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发表时间：
2017
影响因子：
5.6
通讯作者：
Bitto A
中科院分区：
文献类型：
--
作者：
Irrera N;Pizzino G;Calò M;Pallio G;Mannino F;Famà F;Arcoraci V;Fodale V;David A;Francesca C;Minutoli L;Mazzon E;Bramanti P;Squadrito F;Altavilla D;Bitto A
尽管动物模型提供了各种治疗靶点的令人信服的证据，但创伤性脑损伤(TBI)的治疗仍然难以捉摸。NLRP3(核苷酸结合寡聚化结构域样受体家族含3)炎性小体的激活被认为是脑损伤的关键环节。在脑外伤小鼠模型上，NLRP3被测试为减少神经元丢失和促进功能恢复的潜在靶点。雄性NLRP3-/-小鼠(n=20)和野生型小鼠(n=27)。建立闭合性颅脑损伤模型，评价炎性和细胞凋亡标志物。一组WT小鼠也接受了NLRP3抑制剂Bay 11-7082，以进一步评估这一途径的作用。在脑损伤后24小时，与WT小鼠相比，NLRP3-/-动物表现出较好的认知功能，而且脑损伤较轻，脑组织中的炎性介质减少。在接受颅脑损伤的WT动物中使用Bay 11-7082产生了重叠的结果。在第7天，组织学显示，与WT相比，TBI NLRP3-/-动物的脑结构更保守，损伤更少。我们的研究结果表明，NLRP3通路可能作为脑外伤短期后遗症的分子靶点。
Treatment for traumatic brain injury (TBI) remains elusive despite compelling evidence from animal models for a variety of therapeutic targets. The activation of the NLRP3 (Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome has been proposed as key point in the brain damage associated with TBI. NLRP3 was tested as potential target for reducing neuronal loss and promoting functional recovery in a mouse model of TBI. Male NLRP3-/- (n = 20) and wild type (n = 27) mice were used. A closed TBI model was performed and inflammatory and apoptotic markers were evaluated. A group of WT mice also received BAY 11-7082, a NLRP3 inhibitor, to further evaluate the role of this pathway. At 24 h following TBI NLRP3-/- animals demonstrated a preserved cognitive function as compared to WT mice, additionally brain damage was less severe and the inflammatory mediators were reduced in brain lysates. The administration of BAY 11-7082 in WT animals subjected to TBI produced overlapping results. At day 7 histology revealed a more conserved brain structure with reduced damage in TBI NLRP3-/- animals compared to WT. Our data indicate that the NLRP3 pathway might be exploited as molecular target for the short-term sequelae of TBI.
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影响因子：
2.7
作者：
Dix, SL;Aggleton, JP
通讯作者：
Aggleton, JP
影响因子：
1.9
作者：
KURTH, SM;BIGLER, ED;BLATTER, DD
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作者：
MARMAROU, A;FODA, MAA;DEMETRIADOU, K
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作者：
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