Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice.
Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice.
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DOI：
10.1016/j.bbi.2010.12.008
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发表时间：
2011-07
影响因子：
15.1
通讯作者：
Henkel, Jenny S.
中科院分区：
文献类型：
--
作者：
Beers, David R.;Zhao, Weihua;Liao, Bing;Kano, Osamu;Wang, Jinghong;Huang, Ailing;Appel, Stanley H.;Henkel, Jenny S.
An inflammatory response is a pathological hallmark of amyotrophic lateral sclerosis (ALS), a relentless and devastating degenerative disease of motoneurons. This response is not simply a late consequence of motoneuron degeneration, but actively contributes to the balance between neuroprotection and neurotoxicity; initially infiltrating lymphocytes and microglia slow disease progression, while later, they contribute to the acceleration of disease. Since motor weakness begins in the hindlimbs of ALS mice and only later involves the forelimbs, we determined whether differential protective versus injurious inflammatory responses in the cervical and lumbar spinal cords explained the temporally distinct clinical disease courses between the limbs of these mice. Densitometric evaluation of immunohistochemical sections and quantitative RT-PCR (qRT-PCR) demonstrated that CD68 and CD11c were differentially increased in their spinals cords. qRT-PCR revealed that protective and anti-inflammatory factors, including BDNF, GDNF, and IL-4, were increased in the cervical region compared with the lumbar region. In contrast, the toxic markers TNF-α, IL-1β and NOX2 were not different between ALS mice cervical and lumbar regions. T lymphocytes were observed infiltrating lumbar spinal cords of ALS mice prior to the cervical region; mRNA levels of the transcription factor gata-3 (Th2 response) were differentially elevated in the cervical cord of ALS mice whereas t-bet (Th1 response) was increased in the lumbar cord. These results reinforce the important balance between specific protective/injurious inflammatory immune responses in modulating clinical outcomes and suggest that the delayed forelimb motor weakness in ALS mice is partially explained by augmented protective responses in the cervical spinal cords.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
32.4
作者：
Hegazy, Ahmed N.;Peine, Michael;Loehning, Max
通讯作者：
Loehning, Max
影响因子：
11.2
作者：
Henkel, JS;Engelhardt, JI;Appel, SH
通讯作者：
Appel, SH
DOI：
10.1007/bf00325030
发表时间：
1968-01-01
期刊：
ZEITSCHRIFT FUR ZELLFORSCHUNG UND MIKROSKOPISCHE ANATOMIE
影响因子：
--
作者：
BLINZING.K;KREUTZBE.G
通讯作者：
KREUTZBE.G