Immediate Splenectomy Decreases Mortality and Improves Cognitive Function of Rats After Severe Traumatic Brain Injury

Mei, Li; Li, Fēi; Luo, Chunxia; Shan, Yuxi; Zhang, Lijun; Qian, Zhong‐Ming; Zhu, Gang; Lin, Jiangkai; Feng, Hua

doi:10.1097/ta.0b013e3181f30fc9

Cited by 70 publications

(62 citation statements)

References 23 publications

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“…3 B, G). The magnitude of these changes is similar to those previously reported using CCI and weight-drop models (Li et al, 2011;Shein et al, 2014), and are comparable to the levels seen in human TBI patients. For example, we observed that CCI resulted in a mean plasma concentration of IL-6 of 90 pg/ml when assessed 6 h after injury.…”

Section: Discussionsupporting

confidence: 77%

“…The vagus nerve is a key participant in the communication between the brain and components of the immune system, playing an important role in the regulation of peripheral inflammation. Consistent with this, vagus nerve stimulation has been demonstrated to decrease inflammation in models of sepsis and arthritis Kox et al, 2015). For TBI, a brief 10 min stimulation of the vagus nerve immediately before experimental brain injury has been reported to decrease BBB permeability assessed 6 h later (Lopez et al, 2012).…”

Section: Discussionmentioning

confidence: 55%

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Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

et al. 2016

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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 ␣7 (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-␣ and IL-1␤ levels, as well as BBB permeability, were significantly increased in nAChRa7 null mice (Chrna7 Ϫ / Ϫ ) relative to wild-type mice. The administration of exogenous IL-1␤ and TNF-␣ 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 ␣-bungarotoxin increased BBB permeability in brain-injured rats, while PNU-282987 injection decreased such permeability. These effects were not seen when ␣-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.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 55%

Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

et al. 2016

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“…53 Other data suggest that splenectomy prevents IRI in rats 54 and the spleen plays a deleterious role in animal models of stroke. 55,56 These studies portray the spleen as a source of proinflammatory cells that propagate ischemic tissue injury. By contrast, results from our study (showing that prior splenectomy did not reduce the development of IRI) and others 57 reveal a beneficial, anti-inflammatory role of the spleen.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

Gigliotti

Huang

et al. 2013

Journal of the American Society of Nephrology

159

200

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AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b + Ly6G high neutrophils and CD11b + F4/80 high myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4 + T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the a7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway.

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“…Splenectomy has also proven to be beneficial in other types of brain injuries, such as hemorrhagic stroke and traumatic brain injury. [11][12][13][14] In fact, the splenic response to ischemic injury occurs in organs throughout the body. Researchers in the field of liver injury were among the first to report that removal of the spleen before ischemia reperfusion injury to liver is hepatoprotective.…”

Section: Introductionmentioning

confidence: 99%

The Role of the Spleen in Ischemic Stroke

Pennypacker

Offner

2014

J Cereb Blood Flow Metab

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Immediate Splenectomy Decreases Mortality and Improves Cognitive Function of Rats After Severe Traumatic Brain Injury

Abstract: Our study demonstrates that splenectomy has a protective effect on rats with severe TBI by inhibiting proinflammatory cytokines, including IL-1β, TNF-α, and IL-6, both systematically and locally in the injured brain, hence leading to a decreased mortality and improved cognitive function.

Cited by 70 publications

References 23 publications

Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

The Role of the Spleen in Ischemic Stroke

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