Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice
ABSTRACT Background The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut fl...
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| Veröffentlicht in: | CNS neuroscience & therapeutics 2024-11, Vol.30 (11), p.e70078-n/a |
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| creator | Shakoor, Muhammad Usman Tareen, Fashwa Khan Rehman, Zohabia Saghir, Khaled Ahmed Ashraf, Waseem Anjum, Syed Muhammad Muneeb Ahmad, Tanveer Alqahtani, Faleh Imran, Imran |
| description | ABSTRACT
Background
The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.
Methods
In the current study, we investigated the impact of long‐term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony‐forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non‐treated animals.
Results
Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ‐induced neuropsychiatric disturbances such as anxiety and depressive‐like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network‐driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).
Conclusion
Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti‐seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug‐resistant seizures.
Outcomes from this study provide supportive evidence in favor of probiotic‐rich supplementation as an adjunctive therapy with existing antiseizure medications as these commensal bacteria might provide prophylaxis against intractable seizures, particularly in predisposed individuals. |
| doi_str_mv | 10.1111/cns.70078 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11520030</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3121591667</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2998-ccd1dd42592bb04a6c0a79528f20e9b4205b9be706653ff1aa644b767edafe1a3</originalsourceid><addsrcrecordid>eNp1ksFu1DAQhiMEoqVw4AWQJS4gdVvbiZP4hLorKBXdUqlFHK2JM8m6ytrFdha2pz4CEk_Eq_RJMGypAAlfbM18_ucf6c-yp4zusXT2tQ17FaVVfS_bZpUQEyELef_undOt7FEIF5SWvJb1w2wrl0VFGafb2fdT7xrjotGBNGsyd-04QDS2J4djvLn-NvVgLDn4YgI5dz3GBXry0cQFmXqzAg8aIyzJ3ETTQ0RyhuZq9EiSau8xBOPsLpniAlbGeRjIkdXO9n5MPIZdArZNKK7QRmzJCY7etdijRZ88OEvS6NPUWw-pFDF6uHID3lx_fWdsO6Qfc6PxcfaggyHgk9t7J_vw5vX57O3k-P3h0ezgeKK5lPVE65a1bcGF5E1DCyg1hUoKXnecomwKTkUjG6xoWYq86xhAWRRNVVbYQocM8p3s1Ub3cmyW2OrkK22kLr1Zgl8rB0b93bFmoXq3UowJTmlOk8KLWwXvPo0YolqaoHEYwKIbg8oZZ0KysqwS-vwf9MKN3qb9ElXQshaSFol6uaG0dyF47O7cMKp-JkOlZKhfyUjssz_t35G_o5CA_Q3w2Qy4_r-Smp2cbSR_ABDkyqo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3140685904</pqid></control><display><type>article</type><title>Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Shakoor, Muhammad Usman ; Tareen, Fashwa Khan ; Rehman, Zohabia ; Saghir, Khaled Ahmed ; Ashraf, Waseem ; Anjum, Syed Muhammad Muneeb ; Ahmad, Tanveer ; Alqahtani, Faleh ; Imran, Imran</creator><creatorcontrib>Shakoor, Muhammad Usman ; Tareen, Fashwa Khan ; Rehman, Zohabia ; Saghir, Khaled Ahmed ; Ashraf, Waseem ; Anjum, Syed Muhammad Muneeb ; Ahmad, Tanveer ; Alqahtani, Faleh ; Imran, Imran</creatorcontrib><description>ABSTRACT
Background
The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.
Methods
In the current study, we investigated the impact of long‐term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony‐forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non‐treated animals.
Results
Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ‐induced neuropsychiatric disturbances such as anxiety and depressive‐like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network‐driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).
Conclusion
Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti‐seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug‐resistant seizures.
Outcomes from this study provide supportive evidence in favor of probiotic‐rich supplementation as an adjunctive therapy with existing antiseizure medications as these commensal bacteria might provide prophylaxis against intractable seizures, particularly in predisposed individuals.</description><identifier>ISSN: 1755-5930</identifier><identifier>ISSN: 1755-5949</identifier><identifier>EISSN: 1755-5949</identifier><identifier>DOI: 10.1111/cns.70078</identifier><identifier>PMID: 39470120</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Amino acids ; Ammon's horn ; Animals ; Antioxidants ; Behavior ; Behavior, Animal - drug effects ; Brain architecture ; Brain research ; Brain-Gut Axis - drug effects ; Brain-Gut Axis - physiology ; Central nervous system ; Convulsants - toxicity ; Convulsions & seizures ; Cytokines ; Digestive system ; Disease Progression ; Drug dosages ; Dysbacteriosis ; EEG ; Electrodes ; Epilepsy ; Firing pattern ; Gastrointestinal Microbiome - drug effects ; Gastrointestinal Microbiome - physiology ; Gastrointestinal tract ; gut–brain axis ; Homeostasis ; Intestinal microflora ; Kindling, Neurologic - drug effects ; Laboratory animals ; Male ; Metabolism ; Metabolites ; Mice ; Microbiota ; Nervous system ; Neurodegeneration ; Nissl's staining ; Original ; Oxidants ; oxidative stress ; Pentylenetetrazole ; Pentylenetetrazole - toxicity ; Phenotypes ; Physiology ; Probiotics ; Probiotics - pharmacology ; Probiotics - therapeutic use ; PTZ kindling ; Pyrrolidinones - pharmacology ; Pyrrolidinones - therapeutic use ; Seizures ; Surgery</subject><ispartof>CNS neuroscience & therapeutics, 2024-11, Vol.30 (11), p.e70078-n/a</ispartof><rights>2024 The Author(s). published by John Wiley & Sons Ltd.</rights><rights>2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2998-ccd1dd42592bb04a6c0a79528f20e9b4205b9be706653ff1aa644b767edafe1a3</cites><orcidid>0000-0003-1337-8574</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/PMC11520030/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520030/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39470120$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shakoor, Muhammad Usman</creatorcontrib><creatorcontrib>Tareen, Fashwa Khan</creatorcontrib><creatorcontrib>Rehman, Zohabia</creatorcontrib><creatorcontrib>Saghir, Khaled Ahmed</creatorcontrib><creatorcontrib>Ashraf, Waseem</creatorcontrib><creatorcontrib>Anjum, Syed Muhammad Muneeb</creatorcontrib><creatorcontrib>Ahmad, Tanveer</creatorcontrib><creatorcontrib>Alqahtani, Faleh</creatorcontrib><creatorcontrib>Imran, Imran</creatorcontrib><title>Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice</title><title>CNS neuroscience & therapeutics</title><addtitle>CNS Neurosci Ther</addtitle><description>ABSTRACT
Background
The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.
Methods
In the current study, we investigated the impact of long‐term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony‐forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non‐treated animals.
Results
Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ‐induced neuropsychiatric disturbances such as anxiety and depressive‐like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network‐driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).
Conclusion
Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti‐seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug‐resistant seizures.
Outcomes from this study provide supportive evidence in favor of probiotic‐rich supplementation as an adjunctive therapy with existing antiseizure medications as these commensal bacteria might provide prophylaxis against intractable seizures, particularly in predisposed individuals.</description><subject>Amino acids</subject><subject>Ammon's horn</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Behavior</subject><subject>Behavior, Animal - drug effects</subject><subject>Brain architecture</subject><subject>Brain research</subject><subject>Brain-Gut Axis - drug effects</subject><subject>Brain-Gut Axis - physiology</subject><subject>Central nervous system</subject><subject>Convulsants - toxicity</subject><subject>Convulsions & seizures</subject><subject>Cytokines</subject><subject>Digestive system</subject><subject>Disease Progression</subject><subject>Drug dosages</subject><subject>Dysbacteriosis</subject><subject>EEG</subject><subject>Electrodes</subject><subject>Epilepsy</subject><subject>Firing pattern</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Gastrointestinal Microbiome - physiology</subject><subject>Gastrointestinal tract</subject><subject>gut–brain axis</subject><subject>Homeostasis</subject><subject>Intestinal microflora</subject><subject>Kindling, Neurologic - drug effects</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Microbiota</subject><subject>Nervous system</subject><subject>Neurodegeneration</subject><subject>Nissl's staining</subject><subject>Original</subject><subject>Oxidants</subject><subject>oxidative stress</subject><subject>Pentylenetetrazole</subject><subject>Pentylenetetrazole - toxicity</subject><subject>Phenotypes</subject><subject>Physiology</subject><subject>Probiotics</subject><subject>Probiotics - pharmacology</subject><subject>Probiotics - therapeutic use</subject><subject>PTZ kindling</subject><subject>Pyrrolidinones - pharmacology</subject><subject>Pyrrolidinones - therapeutic use</subject><subject>Seizures</subject><subject>Surgery</subject><issn>1755-5930</issn><issn>1755-5949</issn><issn>1755-5949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1ksFu1DAQhiMEoqVw4AWQJS4gdVvbiZP4hLorKBXdUqlFHK2JM8m6ytrFdha2pz4CEk_Eq_RJMGypAAlfbM18_ucf6c-yp4zusXT2tQ17FaVVfS_bZpUQEyELef_undOt7FEIF5SWvJb1w2wrl0VFGafb2fdT7xrjotGBNGsyd-04QDS2J4djvLn-NvVgLDn4YgI5dz3GBXry0cQFmXqzAg8aIyzJ3ETTQ0RyhuZq9EiSau8xBOPsLpniAlbGeRjIkdXO9n5MPIZdArZNKK7QRmzJCY7etdijRZ88OEvS6NPUWw-pFDF6uHID3lx_fWdsO6Qfc6PxcfaggyHgk9t7J_vw5vX57O3k-P3h0ezgeKK5lPVE65a1bcGF5E1DCyg1hUoKXnecomwKTkUjG6xoWYq86xhAWRRNVVbYQocM8p3s1Ub3cmyW2OrkK22kLr1Zgl8rB0b93bFmoXq3UowJTmlOk8KLWwXvPo0YolqaoHEYwKIbg8oZZ0KysqwS-vwf9MKN3qb9ElXQshaSFol6uaG0dyF47O7cMKp-JkOlZKhfyUjssz_t35G_o5CA_Q3w2Qy4_r-Smp2cbSR_ABDkyqo</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Shakoor, Muhammad Usman</creator><creator>Tareen, Fashwa Khan</creator><creator>Rehman, Zohabia</creator><creator>Saghir, Khaled Ahmed</creator><creator>Ashraf, Waseem</creator><creator>Anjum, Syed Muhammad Muneeb</creator><creator>Ahmad, Tanveer</creator><creator>Alqahtani, Faleh</creator><creator>Imran, Imran</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1337-8574</orcidid></search><sort><creationdate>202411</creationdate><title>Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice</title><author>Shakoor, Muhammad Usman ; Tareen, Fashwa Khan ; Rehman, Zohabia ; Saghir, Khaled Ahmed ; Ashraf, Waseem ; Anjum, Syed Muhammad Muneeb ; Ahmad, Tanveer ; Alqahtani, Faleh ; Imran, Imran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2998-ccd1dd42592bb04a6c0a79528f20e9b4205b9be706653ff1aa644b767edafe1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amino acids</topic><topic>Ammon's horn</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Behavior</topic><topic>Behavior, Animal - drug effects</topic><topic>Brain architecture</topic><topic>Brain research</topic><topic>Brain-Gut Axis - drug effects</topic><topic>Brain-Gut Axis - physiology</topic><topic>Central nervous system</topic><topic>Convulsants - toxicity</topic><topic>Convulsions & seizures</topic><topic>Cytokines</topic><topic>Digestive system</topic><topic>Disease Progression</topic><topic>Drug dosages</topic><topic>Dysbacteriosis</topic><topic>EEG</topic><topic>Electrodes</topic><topic>Epilepsy</topic><topic>Firing pattern</topic><topic>Gastrointestinal Microbiome - drug effects</topic><topic>Gastrointestinal Microbiome - physiology</topic><topic>Gastrointestinal tract</topic><topic>gut–brain axis</topic><topic>Homeostasis</topic><topic>Intestinal microflora</topic><topic>Kindling, Neurologic - drug effects</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Mice</topic><topic>Microbiota</topic><topic>Nervous system</topic><topic>Neurodegeneration</topic><topic>Nissl's staining</topic><topic>Original</topic><topic>Oxidants</topic><topic>oxidative stress</topic><topic>Pentylenetetrazole</topic><topic>Pentylenetetrazole - toxicity</topic><topic>Phenotypes</topic><topic>Physiology</topic><topic>Probiotics</topic><topic>Probiotics - pharmacology</topic><topic>Probiotics - therapeutic use</topic><topic>PTZ kindling</topic><topic>Pyrrolidinones - pharmacology</topic><topic>Pyrrolidinones - therapeutic use</topic><topic>Seizures</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shakoor, Muhammad Usman</creatorcontrib><creatorcontrib>Tareen, Fashwa Khan</creatorcontrib><creatorcontrib>Rehman, Zohabia</creatorcontrib><creatorcontrib>Saghir, Khaled Ahmed</creatorcontrib><creatorcontrib>Ashraf, Waseem</creatorcontrib><creatorcontrib>Anjum, Syed Muhammad Muneeb</creatorcontrib><creatorcontrib>Ahmad, Tanveer</creatorcontrib><creatorcontrib>Alqahtani, Faleh</creatorcontrib><creatorcontrib>Imran, Imran</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>CNS neuroscience & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shakoor, Muhammad Usman</au><au>Tareen, Fashwa Khan</au><au>Rehman, Zohabia</au><au>Saghir, Khaled Ahmed</au><au>Ashraf, Waseem</au><au>Anjum, Syed Muhammad Muneeb</au><au>Ahmad, Tanveer</au><au>Alqahtani, Faleh</au><au>Imran, Imran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice</atitle><jtitle>CNS neuroscience & therapeutics</jtitle><addtitle>CNS Neurosci Ther</addtitle><date>2024-11</date><risdate>2024</risdate><volume>30</volume><issue>11</issue><spage>e70078</spage><epage>n/a</epage><pages>e70078-n/a</pages><issn>1755-5930</issn><issn>1755-5949</issn><eissn>1755-5949</eissn><abstract>ABSTRACT
Background
The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.
Methods
In the current study, we investigated the impact of long‐term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony‐forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non‐treated animals.
Results
Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ‐induced neuropsychiatric disturbances such as anxiety and depressive‐like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network‐driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).
Conclusion
Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti‐seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug‐resistant seizures.
Outcomes from this study provide supportive evidence in favor of probiotic‐rich supplementation as an adjunctive therapy with existing antiseizure medications as these commensal bacteria might provide prophylaxis against intractable seizures, particularly in predisposed individuals.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>39470120</pmid><doi>10.1111/cns.70078</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-1337-8574</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | CNS neuroscience & therapeutics, 2024-11, Vol.30 (11), p.e70078-n/a |
| issn | 1755-5930 1755-5949 1755-5949 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Amino acids Ammon's horn Animals Antioxidants Behavior Behavior, Animal - drug effects Brain architecture Brain research Brain-Gut Axis - drug effects Brain-Gut Axis - physiology Central nervous system Convulsants - toxicity Convulsions & seizures Cytokines Digestive system Disease Progression Drug dosages Dysbacteriosis EEG Electrodes Epilepsy Firing pattern Gastrointestinal Microbiome - drug effects Gastrointestinal Microbiome - physiology Gastrointestinal tract gut–brain axis Homeostasis Intestinal microflora Kindling, Neurologic - drug effects Laboratory animals Male Metabolism Metabolites Mice Microbiota Nervous system Neurodegeneration Nissl's staining Original Oxidants oxidative stress Pentylenetetrazole Pentylenetetrazole - toxicity Phenotypes Physiology Probiotics Probiotics - pharmacology Probiotics - therapeutic use PTZ kindling Pyrrolidinones - pharmacology Pyrrolidinones - therapeutic use Seizures Surgery |
| title | Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole‐Kindled Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T13%3A26%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Probiotics%20by%20Modulating%20Gut%E2%80%93Brain%20Axis%20Together%20With%20Brivaracetam%20Mitigate%20Seizure%20Progression,%20Behavioral%20Incongruities,%20and%20Prevented%20Neurodegeneration%20in%20Pentylenetetrazole%E2%80%90Kindled%20Mice&rft.jtitle=CNS%20neuroscience%20&%20therapeutics&rft.au=Shakoor,%20Muhammad%C2%A0Usman&rft.date=2024-11&rft.volume=30&rft.issue=11&rft.spage=e70078&rft.epage=n/a&rft.pages=e70078-n/a&rft.issn=1755-5930&rft.eissn=1755-5949&rft_id=info:doi/10.1111/cns.70078&rft_dat=%3Cproquest_pubme%3E3121591667%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3140685904&rft_id=info:pmid/39470120&rfr_iscdi=true |