Splenectomy protects aged mice from injury after experimental stroke
Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces...
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| Published in | Neurobiology of aging Vol. 61; pp. 102 - 111 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.01.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0197-4580 1558-1497 1558-1497 |
| DOI | 10.1016/j.neurobiolaging.2017.09.022 |
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| Abstract | Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals. |
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| AbstractList | Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals.Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals. Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals. Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy two weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals. |
| Author | Al Mamun, Abdullah Harris, Nia Spiegel, Gabriel McCullough, Louise D. Chauhan, Anjali Zhu, Liang |
| AuthorAffiliation | b University of Connecticut Health Science Center, Farmington, Connecticut, U.S.A a Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX 77030, U.S.A c Memorial Hermann Hospital-Texas Medical Center, Houston, TX 77030, U.S.A d Biostatistics & Epidemiology Research Design Core, Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA |
| AuthorAffiliation_xml | – name: a Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX 77030, U.S.A – name: d Biostatistics & Epidemiology Research Design Core, Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA – name: b University of Connecticut Health Science Center, Farmington, Connecticut, U.S.A – name: c Memorial Hermann Hospital-Texas Medical Center, Houston, TX 77030, U.S.A |
| Author_xml | – sequence: 1 givenname: Anjali surname: Chauhan fullname: Chauhan, Anjali organization: Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA – sequence: 2 givenname: Abdullah surname: Al Mamun fullname: Al Mamun, Abdullah organization: Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA – sequence: 3 givenname: Gabriel surname: Spiegel fullname: Spiegel, Gabriel organization: Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA – sequence: 4 givenname: Nia surname: Harris fullname: Harris, Nia organization: University of Connecticut Health Science Center, Farmington, Connecticut, USA – sequence: 5 givenname: Liang surname: Zhu fullname: Zhu, Liang organization: Biostatistics & Epidemiology Research Design Core, Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA – sequence: 6 givenname: Louise D. surname: McCullough fullname: McCullough, Louise D. email: Louise.D.McCullough@uth.tmc.edu organization: Department of Neurology, the University of Texas McGovern Medical School at Houston, TX, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29059593$$D View this record in MEDLINE/PubMed |
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| Keywords | Splenectomy Middle cerebral artery occlusion model Stroke Immune response Age |
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Immunol. doi: 10.4049/jimmunol.1001271 |
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| Title | Splenectomy protects aged mice from injury after experimental stroke |
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