Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection
Herpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS) inflammatory responses. We...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Behavioural Neurology |
| Online Access: | http://dx.doi.org/10.1155/2017/5238402 |
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| author | Chandran Ramakrishna Mari S. Golub Abby Chiang Teresa Hong Markus Kalkum Edouard M. Cantin |
| author_facet | Chandran Ramakrishna Mari S. Golub Abby Chiang Teresa Hong Markus Kalkum Edouard M. Cantin |
| author_sort | Chandran Ramakrishna |
| collection | DOAJ |
| description | Herpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS) inflammatory responses. We hypothesized that CNS inflammation is casually involved in behavioral abnormalities after HSE and that treatment with ACV and pooled human immunoglobulin (IVIG), an immunomodulatory drug, would improve outcomes compared to mice treated with phosphate buffered saline (PBS) or ACV alone. Anxiety levels were high in HSV-infected PBS and ACV-treated mice compared to mice treated with ACV + IVIG, consistent with reports implicating inflammation in anxiety induced by lipopolysaccharide (LPS) or stress. Female, but not male, PBS-treated mice were cognitively impaired, and unexpectedly, ACV was protective, while the inclusion of IVIG surprisingly antagonized ACV’s beneficial effects. Distinct serum proteomic profiles were observed for male and female mice, and the antagonistic effects of ACV and IVIG on behavior were paralleled by similar changes in the serum proteome of ACV- and ACV + IVIG-treated mice. We conclude that inflammation and other factors mediate HSV-induced behavioral impairments and that the effects of ACV and IVIG on behavior involve novel mechanisms. |
| format | Article |
| id | doaj-art-3e084503bfad41e69603bf2a1c8d8306 |
| institution | Kabale University |
| issn | 0953-4180 1875-8584 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Behavioural Neurology |
| spelling | doaj-art-3e084503bfad41e69603bf2a1c8d83062025-02-03T01:21:34ZengWileyBehavioural Neurology0953-41801875-85842017-01-01201710.1155/2017/52384025238402Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS InfectionChandran Ramakrishna0Mari S. Golub1Abby Chiang2Teresa Hong3Markus Kalkum4Edouard M. Cantin5Department of Molecular Immunology, City of Hope Beckman Research Institute, Duarte, CA, USADepartment of Environmental Toxicology, UC Davis, Davis, CA, USADepartment of Molecular Immunology, City of Hope Beckman Research Institute, Duarte, CA, USADepartment of Molecular Immunology, City of Hope Beckman Research Institute, Duarte, CA, USADepartment of Molecular Immunology, City of Hope Beckman Research Institute, Duarte, CA, USADepartment of Molecular Immunology, City of Hope Beckman Research Institute, Duarte, CA, USAHerpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS) inflammatory responses. We hypothesized that CNS inflammation is casually involved in behavioral abnormalities after HSE and that treatment with ACV and pooled human immunoglobulin (IVIG), an immunomodulatory drug, would improve outcomes compared to mice treated with phosphate buffered saline (PBS) or ACV alone. Anxiety levels were high in HSV-infected PBS and ACV-treated mice compared to mice treated with ACV + IVIG, consistent with reports implicating inflammation in anxiety induced by lipopolysaccharide (LPS) or stress. Female, but not male, PBS-treated mice were cognitively impaired, and unexpectedly, ACV was protective, while the inclusion of IVIG surprisingly antagonized ACV’s beneficial effects. Distinct serum proteomic profiles were observed for male and female mice, and the antagonistic effects of ACV and IVIG on behavior were paralleled by similar changes in the serum proteome of ACV- and ACV + IVIG-treated mice. We conclude that inflammation and other factors mediate HSV-induced behavioral impairments and that the effects of ACV and IVIG on behavior involve novel mechanisms.http://dx.doi.org/10.1155/2017/5238402 |
| spellingShingle | Chandran Ramakrishna Mari S. Golub Abby Chiang Teresa Hong Markus Kalkum Edouard M. Cantin Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection Behavioural Neurology |
| title | Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection |
| title_full | Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection |
| title_fullStr | Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection |
| title_full_unstemmed | Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection |
| title_short | Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection |
| title_sort | effects of acyclovir and ivig on behavioral outcomes after hsv1 cns infection |
| url | http://dx.doi.org/10.1155/2017/5238402 |
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