A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics
The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies...
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| Veröffentlicht in: | Experimental Animals 2020, Vol.69(1), pp.92-103 |
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| creator | Bordoni, Luca Jiménez, Eugenio Gutiérrez Nielsen, Søren Østergaard, Leif Frische, Sebastian |
| description | The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication. |
| doi_str_mv | 10.1538/expanim.19-0040 |
| format | Article |
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This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.</description><identifier>ISSN: 1341-1357</identifier><identifier>EISSN: 1881-7122</identifier><identifier>DOI: 10.1538/expanim.19-0040</identifier><identifier>PMID: 31534063</identifier><language>eng</language><publisher>TOKYO: Japanese Association for Laboratory Animal Science</publisher><subject>Acetic acid ; Animals ; Antidiuretic Agents - administration & dosage ; Antidiuretics ; Blood pressure ; Body weight ; Brain stem ; Deamino Arginine Vasopressin - administration & dosage ; Desmopressin ; Disease Models, Animal ; Diuresis ; Extreme values ; Hyponatremia ; Hyponatremia - chemically induced ; Hyponatremia - physiopathology ; Injection ; Injections, Intraperitoneal ; Intoxication ; Intracranial Hypertension - chemically induced ; Intracranial Hypertension - physiopathology ; Intracranial Pressure ; Life Sciences & Biomedicine ; Male ; Mice ; Mice, Inbred C57BL ; mouse model ; Original ; Potassium chloride ; Science & Technology ; Side effects ; Sodium bicarbonate ; Sodium chloride ; Urine ; Veterinary Sciences ; water intoxication ; Water Intoxication - physiopathology ; Zoology</subject><ispartof>Experimental Animals, 2020, Vol.69(1), pp.92-103</ispartof><rights>2020 Japanese Association for Laboratory Animal Science</rights><rights>Copyright Japan Science and Technology Agency 2020</rights><rights>2020 Japanese Association for Laboratory Animal Science 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>5</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000509786900011</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c573t-b8f391300c573143b0594f779d97d6e33581f37f43e57766bb4e33f3019a6a173</citedby><cites>FETCH-LOGICAL-c573t-b8f391300c573143b0594f779d97d6e33581f37f43e57766bb4e33f3019a6a173</cites><orcidid>0000-0002-7619-605X ; 0000-0002-0270-3602 ; 0000-0002-2428-0874</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004811/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004811/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,887,1887,27933,27934,28257,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31534063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bordoni, Luca</creatorcontrib><creatorcontrib>Jiménez, Eugenio Gutiérrez</creatorcontrib><creatorcontrib>Nielsen, Søren</creatorcontrib><creatorcontrib>Østergaard, Leif</creatorcontrib><creatorcontrib>Frische, Sebastian</creatorcontrib><title>A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics</title><title>Experimental Animals</title><addtitle>EXP ANIM TOKYO</addtitle><addtitle>Exp Anim</addtitle><description>The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.</description><subject>Acetic acid</subject><subject>Animals</subject><subject>Antidiuretic Agents - administration & dosage</subject><subject>Antidiuretics</subject><subject>Blood pressure</subject><subject>Body weight</subject><subject>Brain stem</subject><subject>Deamino Arginine Vasopressin - administration & dosage</subject><subject>Desmopressin</subject><subject>Disease Models, Animal</subject><subject>Diuresis</subject><subject>Extreme values</subject><subject>Hyponatremia</subject><subject>Hyponatremia - chemically induced</subject><subject>Hyponatremia - physiopathology</subject><subject>Injection</subject><subject>Injections, Intraperitoneal</subject><subject>Intoxication</subject><subject>Intracranial Hypertension - chemically induced</subject><subject>Intracranial Hypertension - physiopathology</subject><subject>Intracranial Pressure</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>mouse model</subject><subject>Original</subject><subject>Potassium chloride</subject><subject>Science & Technology</subject><subject>Side effects</subject><subject>Sodium bicarbonate</subject><subject>Sodium chloride</subject><subject>Urine</subject><subject>Veterinary Sciences</subject><subject>water intoxication</subject><subject>Water Intoxication - physiopathology</subject><subject>Zoology</subject><issn>1341-1357</issn><issn>1881-7122</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhSMEoqVw5oYscURp7TiJ4wtStWoBqRIXOFuOM-56ldiL7bDtr-GvdnazLHDj4owz33se-xXFW0YvWcO7K3jYau-mSyZLSmv6rDhnXcdKwarqOda8ZiXjjTgrXqW0obQSopIvizOO4pq2_Lz4dU087Aj6QHQT-KxHMoU5Aa4DjCRYstMZInE-hwdndHbBk53La5LmlLXzMGDPRNDpUOWoTcSZ0GcbIaU5AtF-IJMbB7J-3Aavc4TJ6YNJmDNJbgAC1oLJaX-e9tkNDnXZmfS6eGH1mODN8XtRfL-9-bb6XN59_fRldX1XmkbwXPad5ZJxSvdbVvOeNrK2QshBiqEFzpuOWS5szaERom37vsafllMmdauZ4BfFx8V3O_cTDAb2FxnVFh9Fx0cVtFP_drxbq_vwUwl8944xNHh_NIjhxwwpq02Yo8eZVcVr2fGqozVSVwtlYkgpgj2dwKjaJ6qOiSom1T5RVLz7e7AT_ztCBLoF2EEfbDIOvIETRiltqBRdK7FibOXyIcFVmH1G6Yf_lyJ9s9AbzP3-D6cjBjXCafJWKnZYlhuc-matowLPnwBFpNzA</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Bordoni, Luca</creator><creator>Jiménez, Eugenio Gutiérrez</creator><creator>Nielsen, Søren</creator><creator>Østergaard, Leif</creator><creator>Frische, Sebastian</creator><general>Japanese Association for Laboratory Animal Science</general><general>Int Press Editing Centre Inc</general><general>Japan Science and Technology Agency</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7619-605X</orcidid><orcidid>https://orcid.org/0000-0002-0270-3602</orcidid><orcidid>https://orcid.org/0000-0002-2428-0874</orcidid></search><sort><creationdate>20200101</creationdate><title>A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics</title><author>Bordoni, Luca ; Jiménez, Eugenio Gutiérrez ; Nielsen, Søren ; Østergaard, Leif ; Frische, Sebastian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-b8f391300c573143b0594f779d97d6e33581f37f43e57766bb4e33f3019a6a173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acetic acid</topic><topic>Animals</topic><topic>Antidiuretic Agents - administration & dosage</topic><topic>Antidiuretics</topic><topic>Blood pressure</topic><topic>Body weight</topic><topic>Brain stem</topic><topic>Deamino Arginine Vasopressin - administration & dosage</topic><topic>Desmopressin</topic><topic>Disease Models, Animal</topic><topic>Diuresis</topic><topic>Extreme values</topic><topic>Hyponatremia</topic><topic>Hyponatremia - chemically induced</topic><topic>Hyponatremia - physiopathology</topic><topic>Injection</topic><topic>Injections, Intraperitoneal</topic><topic>Intoxication</topic><topic>Intracranial Hypertension - chemically induced</topic><topic>Intracranial Hypertension - physiopathology</topic><topic>Intracranial Pressure</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>mouse model</topic><topic>Original</topic><topic>Potassium chloride</topic><topic>Science & Technology</topic><topic>Side effects</topic><topic>Sodium bicarbonate</topic><topic>Sodium chloride</topic><topic>Urine</topic><topic>Veterinary Sciences</topic><topic>water intoxication</topic><topic>Water Intoxication - physiopathology</topic><topic>Zoology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bordoni, Luca</creatorcontrib><creatorcontrib>Jiménez, Eugenio Gutiérrez</creatorcontrib><creatorcontrib>Nielsen, Søren</creatorcontrib><creatorcontrib>Østergaard, Leif</creatorcontrib><creatorcontrib>Frische, Sebastian</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental Animals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bordoni, Luca</au><au>Jiménez, Eugenio Gutiérrez</au><au>Nielsen, Søren</au><au>Østergaard, Leif</au><au>Frische, Sebastian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics</atitle><jtitle>Experimental Animals</jtitle><stitle>EXP ANIM TOKYO</stitle><addtitle>Exp Anim</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>69</volume><issue>1</issue><spage>92</spage><epage>103</epage><pages>92-103</pages><issn>1341-1357</issn><eissn>1881-7122</eissn><abstract>The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.</abstract><cop>TOKYO</cop><pub>Japanese Association for Laboratory Animal Science</pub><pmid>31534063</pmid><doi>10.1538/expanim.19-0040</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-7619-605X</orcidid><orcidid>https://orcid.org/0000-0002-0270-3602</orcidid><orcidid>https://orcid.org/0000-0002-2428-0874</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acetic acid Animals Antidiuretic Agents - administration & dosage Antidiuretics Blood pressure Body weight Brain stem Deamino Arginine Vasopressin - administration & dosage Desmopressin Disease Models, Animal Diuresis Extreme values Hyponatremia Hyponatremia - chemically induced Hyponatremia - physiopathology Injection Injections, Intraperitoneal Intoxication Intracranial Hypertension - chemically induced Intracranial Hypertension - physiopathology Intracranial Pressure Life Sciences & Biomedicine Male Mice Mice, Inbred C57BL mouse model Original Potassium chloride Science & Technology Side effects Sodium bicarbonate Sodium chloride Urine Veterinary Sciences water intoxication Water Intoxication - physiopathology Zoology |
| title | A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics |
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