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- W2289804617 abstract "Traumatic brain injury (TBI) is a major human health concern that has the greatest impact on young men and women. The breakdown of the blood–brain barrier (BBB) is an important pathological consequence of TBI that initiates secondary processes, including infiltration of inflammatory cells, which can exacerbate brain inflammation and contribute to poor outcome. While the role of inflammation within the injured brain has been examined in some detail, the contribution of peripheral/systemic inflammation to TBI pathophysiology is largely unknown. Recent studies have implicated vagus nerve regulation of splenic cholinergic nicotinic acetylcholine receptor α7 (nAChRa7) signaling in the regulation of systemic inflammation. However, it is not known whether this mechanism plays a role in TBI-triggered inflammation and BBB breakdown. Following TBI, we observed that plasma TNF-α and IL-1β levels, as well as BBB permeability, were significantly increased in nAChRa7 null mice ( Chrna7 −/− ) relative to wild-type mice. The administration of exogenous IL-1β and TNF-α to brain-injured animals worsened Evans Blue dye extravasation, suggesting that systemic inflammation contributes to TBI-triggered BBB permeability. Systemic administration of the nAChRa7 agonist PNU-282987 or the positive allosteric modulator PNU-120596 significantly attenuated TBI-triggered BBB compromise. Supporting a role for splenic nAChRa7 receptors, we demonstrate that splenic injection of the nicotinic receptor blocker α-bungarotoxin increased BBB permeability in brain-injured rats, while PNU-282987 injection decreased such permeability. These effects were not seen when α-bungarotoxin or PNU-282987 were administered to splenectomized, brain-injured rats. Together, these findings support the short-term use of nAChRa7-activating agents as a strategy to reduce TBI-triggered BBB permeability. SIGNIFICANCE STATEMENT Breakdown of the blood–brain barrier (BBB) in response to traumatic brain injury (TBI) allows for the accumulation of circulating fluids and proinflammatory cells in the injured brain. These processes can exacerbate TBI pathology and outcome. While the role of inflammation in the injured tissue has been examined in some detail, the contribution of peripheral inflammation in BBB breakdown and ensuing pathology has not been well defined. We present experimental evidence to indicate that the stimulation of nicotinic acetylcholine α7 receptors (nAChRa7s) can reduce peripheral inflammation and BBB breakdown after TBI. These results suggest that activators of nAChRa7 may have therapeutic utility for the treatment of TBI." @default.
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- W2289804617 date "2016-03-02" @default.
- W2289804617 modified "2023-10-18" @default.
- W2289804617 title "Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury" @default.
- W2289804617 cites W1488659741 @default.
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- W2289804617 cites W157415499 @default.
- W2289804617 cites W1814430977 @default.
- W2289804617 cites W1901457319 @default.
- W2289804617 cites W1964072039 @default.
- W2289804617 cites W1966528088 @default.
- W2289804617 cites W1970214664 @default.
- W2289804617 cites W1970885006 @default.
- W2289804617 cites W1971773216 @default.
- W2289804617 cites W1978876398 @default.
- W2289804617 cites W1980654171 @default.
- W2289804617 cites W1983615367 @default.
- W2289804617 cites W1987396857 @default.
- W2289804617 cites W1987476809 @default.
- W2289804617 cites W1988610853 @default.
- W2289804617 cites W1996566544 @default.
- W2289804617 cites W2002968561 @default.
- W2289804617 cites W2003923114 @default.
- W2289804617 cites W2007143131 @default.
- W2289804617 cites W2009317569 @default.
- W2289804617 cites W2013700204 @default.
- W2289804617 cites W2015917405 @default.
- W2289804617 cites W2016451391 @default.
- W2289804617 cites W2018067227 @default.
- W2289804617 cites W2025840069 @default.
- W2289804617 cites W2034259049 @default.
- W2289804617 cites W2035493528 @default.
- W2289804617 cites W2035565598 @default.
- W2289804617 cites W2043508445 @default.
- W2289804617 cites W2046775696 @default.
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- W2289804617 cites W2063858768 @default.
- W2289804617 cites W2066895427 @default.
- W2289804617 cites W2067629356 @default.
- W2289804617 cites W2068274425 @default.
- W2289804617 cites W2069368135 @default.
- W2289804617 cites W2071950202 @default.
- W2289804617 cites W2073295417 @default.
- W2289804617 cites W2074510736 @default.
- W2289804617 cites W2075782105 @default.
- W2289804617 cites W2079730381 @default.
- W2289804617 cites W2084969905 @default.
- W2289804617 cites W2086659521 @default.
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- W2289804617 cites W2105455720 @default.
- W2289804617 cites W2117992648 @default.
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- W2289804617 cites W2140178129 @default.
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- W2289804617 cites W2157968665 @default.
- W2289804617 cites W2171301715 @default.
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- W2289804617 doi "https://doi.org/10.1523/jneurosci.3197-15.2016" @default.
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