A Modified Ultrasound Regimen Reduces Kidney Ischemia Reperfusion Injury in Mice via Splenic Cholinergic Modulation

Joseph C. Gigliotti; Kryt Chattrabhuti; Liping Huang; Amandeep Bajwa; Hong Ye; Sangju Lee; Diane L. Rosin; Alexander L. Klibanov; Kambiz Kalantari; Mark D. Okusa

A Modified Ultrasound Regimen Reduces Kidney Ischemia Reperfusion Injury in Mice via Splenic Cholinergic Modulation

Joseph C. Gigliotti, Kryt Chattrabhuti, Liping Huang, Amandeep Bajwa, Hong Ye, Sangju Lee, Diane L. Rosin, Alexander L. Klibanov, Kambiz Kalantari, Mark D. Okusa

College of Osteopathic Medicine

Research output: Contribution to conference › Presentation

Abstract

   Background:  Activation of innate immunity is key in the pathogenesis of ischemia reperfusion injury (IRI). Previous research suggests that ultrasound (US) exposure modulates the immune response. Our hypothesis is that prior exposure to US will reduce the severity of kidney injury in a mouse model of IRI.
   Methods:  Anesthetized male C57BL/6 mice were exposed to US (frequency: 7MHz; MI: 1.2). Mice underwent bilateral renal IRI 24 hr after US exposure. After reperfusion, tissue samples were collected for plasma creatinine (PCr), renal tissue histology, and flow cytometry. In subsequent studies, TNFα was quantified in LPS treated splenocytes isolated 24 hr after US exposure. In others, mice underwent splenectomy 7 d prior to US and IRI. To determine the role of cholinergic signaling in US prevention of IRI, the α-7 nicotinic antagonist α-bungarotoxin (BT) was administered i.v. 30 min prior to US.
   Results:  Following IRI, US treated mice had reduced PCR (P<0.001), tubular damage (P<0.001), and kidney leukocyte infiltration (P=0.003) compared to mice receiving IRI alone. Protection from IRI (P<0.005; PCr) lasted up to 2-3 d following US exposure. Splenocytes from US treated mice produce 75% less TNFα in response to ex vivo LPS stimulation compared to non-US treated animals. Furthermore, prior splenectomy (P=0.01) removed the protective effect of US. BT administration also abolished US protection from IRI.
   Conclusions:  Our data is consistent with the hypothesis that US mediated kidney tissue protection occurs via activation of the splenic cholinergic anti-inflammatory pathway. We believe that this finding could have an important impact in attenuating human acute kidney injury given the routine noninvasive nature of US, which is a safe, portable and an inexpensive method of immune modulation

Original language	American English
State	Published - 2012
Event	American Society of Nephrology Annual Meeting 2012 - San Diego, CA Duration: Jan 1 2012 → …

Conference

Conference	American Society of Nephrology Annual Meeting 2012
Period	1/1/12 → …

Disciplines

Medicine and Health Sciences

Cite this

@conference{ae0527033b074eccae25d5adea3ea3b7,

title = "A Modified Ultrasound Regimen Reduces Kidney Ischemia Reperfusion Injury in Mice via Splenic Cholinergic Modulation",

abstract = " Background: Activation of innate immunity is key in the pathogenesis of ischemia reperfusion injury (IRI). Previous research suggests that ultrasound (US) exposure modulates the immune response. Our hypothesis is that prior exposure to US will reduce the severity of kidney injury in a mouse model of IRI. Methods: Anesthetized male C57BL/6 mice were exposed to US (frequency: 7MHz; MI: 1.2). Mice underwent bilateral renal IRI 24 hr after US exposure. After reperfusion, tissue samples were collected for plasma creatinine (PCr), renal tissue histology, and flow cytometry. In subsequent studies, TNFα was quantified in LPS treated splenocytes isolated 24 hr after US exposure. In others, mice underwent splenectomy 7 d prior to US and IRI. To determine the role of cholinergic signaling in US prevention of IRI, the α-7 nicotinic antagonist α-bungarotoxin (BT) was administered i.v. 30 min prior to US. Results: Following IRI, US treated mice had reduced PCR (P<0.001), tubular damage (P<0.001), and kidney leukocyte infiltration (P=0.003) compared to mice receiving IRI alone. Protection from IRI (P<0.005; PCr) lasted up to 2-3 d following US exposure. Splenocytes from US treated mice produce 75% less TNFα in response to ex vivo LPS stimulation compared to non-US treated animals. Furthermore, prior splenectomy (P=0.01) removed the protective effect of US. BT administration also abolished US protection from IRI. Conclusions: Our data is consistent with the hypothesis that US mediated kidney tissue protection occurs via activation of the splenic cholinergic anti-inflammatory pathway. We believe that this finding could have an important impact in attenuating human acute kidney injury given the routine noninvasive nature of US, which is a safe, portable and an inexpensive method of immune modulation",

author = "Gigliotti, {Joseph C.} and Kryt Chattrabhuti and Liping Huang and Amandeep Bajwa and Hong Ye and Sangju Lee and Rosin, {Diane L.} and Klibanov, {Alexander L.} and Kambiz Kalantari and Okusa, {Mark D.}",

year = "2012",

language = "American English",

note = "American Society of Nephrology Annual Meeting 2012 ; Conference date: 01-01-2012",

}

TY - CONF

T1 - A Modified Ultrasound Regimen Reduces Kidney Ischemia Reperfusion Injury in Mice via Splenic Cholinergic Modulation

AU - Gigliotti, Joseph C.

AU - Chattrabhuti, Kryt

AU - Huang, Liping

AU - Bajwa, Amandeep

AU - Ye, Hong

AU - Lee, Sangju

AU - Rosin, Diane L.

AU - Klibanov, Alexander L.

AU - Kalantari, Kambiz

AU - Okusa, Mark D.

PY - 2012

Y1 - 2012

N2 - Background: Activation of innate immunity is key in the pathogenesis of ischemia reperfusion injury (IRI). Previous research suggests that ultrasound (US) exposure modulates the immune response. Our hypothesis is that prior exposure to US will reduce the severity of kidney injury in a mouse model of IRI. Methods: Anesthetized male C57BL/6 mice were exposed to US (frequency: 7MHz; MI: 1.2). Mice underwent bilateral renal IRI 24 hr after US exposure. After reperfusion, tissue samples were collected for plasma creatinine (PCr), renal tissue histology, and flow cytometry. In subsequent studies, TNFα was quantified in LPS treated splenocytes isolated 24 hr after US exposure. In others, mice underwent splenectomy 7 d prior to US and IRI. To determine the role of cholinergic signaling in US prevention of IRI, the α-7 nicotinic antagonist α-bungarotoxin (BT) was administered i.v. 30 min prior to US. Results: Following IRI, US treated mice had reduced PCR (P<0.001), tubular damage (P<0.001), and kidney leukocyte infiltration (P=0.003) compared to mice receiving IRI alone. Protection from IRI (P<0.005; PCr) lasted up to 2-3 d following US exposure. Splenocytes from US treated mice produce 75% less TNFα in response to ex vivo LPS stimulation compared to non-US treated animals. Furthermore, prior splenectomy (P=0.01) removed the protective effect of US. BT administration also abolished US protection from IRI. Conclusions: Our data is consistent with the hypothesis that US mediated kidney tissue protection occurs via activation of the splenic cholinergic anti-inflammatory pathway. We believe that this finding could have an important impact in attenuating human acute kidney injury given the routine noninvasive nature of US, which is a safe, portable and an inexpensive method of immune modulation

AB - Background: Activation of innate immunity is key in the pathogenesis of ischemia reperfusion injury (IRI). Previous research suggests that ultrasound (US) exposure modulates the immune response. Our hypothesis is that prior exposure to US will reduce the severity of kidney injury in a mouse model of IRI. Methods: Anesthetized male C57BL/6 mice were exposed to US (frequency: 7MHz; MI: 1.2). Mice underwent bilateral renal IRI 24 hr after US exposure. After reperfusion, tissue samples were collected for plasma creatinine (PCr), renal tissue histology, and flow cytometry. In subsequent studies, TNFα was quantified in LPS treated splenocytes isolated 24 hr after US exposure. In others, mice underwent splenectomy 7 d prior to US and IRI. To determine the role of cholinergic signaling in US prevention of IRI, the α-7 nicotinic antagonist α-bungarotoxin (BT) was administered i.v. 30 min prior to US. Results: Following IRI, US treated mice had reduced PCR (P<0.001), tubular damage (P<0.001), and kidney leukocyte infiltration (P=0.003) compared to mice receiving IRI alone. Protection from IRI (P<0.005; PCr) lasted up to 2-3 d following US exposure. Splenocytes from US treated mice produce 75% less TNFα in response to ex vivo LPS stimulation compared to non-US treated animals. Furthermore, prior splenectomy (P=0.01) removed the protective effect of US. BT administration also abolished US protection from IRI. Conclusions: Our data is consistent with the hypothesis that US mediated kidney tissue protection occurs via activation of the splenic cholinergic anti-inflammatory pathway. We believe that this finding could have an important impact in attenuating human acute kidney injury given the routine noninvasive nature of US, which is a safe, portable and an inexpensive method of immune modulation

M3 - Presentation

T2 - American Society of Nephrology Annual Meeting 2012

Y2 - 1 January 2012

ER -