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Article ; Online: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

Maglakelidze, Natella / Manto, Kristen M / Craig, Timothy J

Pulmonary therapy

2020 Volume 6, Issue 2, Page(s) 169–176

Abstract: Introduction: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory ... ...

Abstract	Introduction: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. Methods: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. Results: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.
Keywords	covid19
Language	English
Publishing date	2020-05-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2364-1746
ISSN (online)	2364-1746
DOI	10.1007/s41030-020-00118-5
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Article: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

Maglakelidze, Natella / Manto, Kristen M / Craig, Timothy J

Abstract: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory ... ...

Abstract	INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32405877
Database	COVID19

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Article ; Online: A Review

Maglakelidze, Natella / Manto, Kristen M. / Craig, Timothy J.

Pulmonary Therapy ; ISSN 2364-1754 2364-1746

Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

2020

Keywords	covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
DOI	10.1007/s41030-020-00118-5
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Article ; Online: Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury.

Manto, Kristen M / Govindappa, Prem Kumar / Martinazzi, Brandon / Han, Aijie / Hegarty, John P / Koroneos, Zachary / Talukder, M A Hassan / Elfar, John C

Journal of nanobiotechnology

2022 Volume 20, Issue 1, Page(s) 461

Abstract: Background: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers ... ...

Abstract	Background: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. Methods: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. Results: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. Conclusion: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.
MeSH term(s)	Mice ; Animals ; Peripheral Nerve Injuries/drug therapy ; Delayed-Action Preparations/pharmacology ; Nerve Regeneration ; Sciatic Neuropathy/drug therapy ; Erythropoietin/pharmacology ; Erythropoietin/chemistry ; Erythropoietin/therapeutic use ; Crush Injuries/drug therapy
Chemical Substances	Delayed-Action Preparations ; Erythropoietin (11096-26-7)
Language	English
Publishing date	2022-10-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-022-01666-5
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Article ; Online: Cost-Effective Modeling of Thromboembolic Chemoprophylaxis for Total Ankle Arthroplasty.

Martinazzi, Brandon J / Kirchner, Gregory J / Stauch, Christopher M / Lorenz, F Jeffrey / Manto, Kristen M / Bonaddio, Vincenzo / Koroneos, Zachary / Aynardi, Michael C

Foot & ankle international

2022 Volume 43, Issue 10, Page(s) 1379–1384

Abstract: Background: Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy ...

Abstract	Background: Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model. Methods: The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective. Results: The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates. Conclusion: Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.
MeSH term(s)	Ankle ; Anticoagulants/therapeutic use ; Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Aspirin/therapeutic use ; Chemoprevention/adverse effects ; Cost-Benefit Analysis ; Enoxaparin/therapeutic use ; Humans ; Postoperative Complications/etiology ; Rivaroxaban/therapeutic use ; Venous Thromboembolism/etiology ; Venous Thromboembolism/prevention & control ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Enoxaparin ; Warfarin (5Q7ZVV76EI) ; Rivaroxaban (9NDF7JZ4M3) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2022-07-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1183283-6
ISSN	1944-7876 ; 1071-1007
ISSN (online)	1944-7876
ISSN	1071-1007
DOI	10.1177/10711007221112922
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Article ; Online: Biomechanical Comparison of Fiber Tape Device Versus Transarticular Screws for Ligamentous Lisfranc Injury in a Cadaveric Model.

Koroneos, Zachary A / Manto, Kristen M / Martinazzi, Brandon J / Stauch, Chris / Bifano, Shawn M / Kunselman, Allen R / Lewis, Gregory S / Aynardi, Michael

The American journal of sports medicine

2022 Volume 50, Issue 12, Page(s) 3299–3307

Abstract: Background: The preferred method of fixation and surgical treatment for ligamentous Lisfranc injuries is controversial. Transarticular screws, bridge plating, fusion, and flexible fixation have been described, yet none have demonstrated superiority. ... ...

Abstract	Background: The preferred method of fixation and surgical treatment for ligamentous Lisfranc injuries is controversial. Transarticular screws, bridge plating, fusion, and flexible fixation have been described, yet none have demonstrated superiority. Furthermore, screw fixation and plating often require secondary surgery to remove implants, leading surgeons to seek alternative fixation methods. Purpose: To compare transarticular screws and a fiber tape construct under a spectrum of biomechanical loads by evaluating the diastasis at 3 joints in the Lisfranc complex. Study design: Controlled laboratory study. Methods: Eight matched pairs of fresh, previously frozen lower extremity cadaveric specimens were fixed with either 2 cannulated transarticular crossed screws or a fiber tape construct with a supplemental intercuneiform limb. The diastasis between bones was measured at 3 midfoot joints in the Lisfranc complex: the Lisfranc articulation, the second tarsometatarsal joint, and the intercuneiform joint. Measurements were obtained for the preinjured, injured, and fixation conditions under static loading at 50% donor body weight. Specimens then underwent cyclic loading performed at 1 Hz and 100 cycles, based on 100-N stepwise increases in ground-reaction force from 100 to 2000 N, to simulate postoperative loading from the partial weightbearing stage to high-energy activities. Failure of fixation was defined as diastasis ≥2 mm at the Lisfranc articulation (second metatarsal-medial cuneiform joint). Results: There were no significant differences in diastasis detected at the Lisfranc articulation or the intercuneiform joint throughout all loading cycles between groups. All specimens endured loading up to 50% body weight + 1400 N. Up to and including this stage, there were 2 failures in the cannulated transarticular crossed-screw group and none in the fiber tape group. Conclusion: The fiber tape construct with a supplemental intercuneiform limb, which does not require later removal, may provide comparable biomechanical stability to cannulated transarticular crossed screws, even at higher loads. Clinical relevance: Ligamentous Lisfranc injuries are common among athletes. Therefore, biomechanical evaluations are necessary to determine stable constructs that can limit the time to return to play. This study compares the biomechanical stability of 2 methods of fixation for ligamentous injury through a wide spectrum of loading, including those experienced by athletes.
MeSH term(s)	Biomechanical Phenomena ; Body Weight ; Bone Screws ; Cadaver ; Humans ; Ligaments, Articular/injuries ; Ligaments, Articular/surgery ; Metatarsal Bones/injuries ; Metatarsal Bones/surgery
Language	English
Publishing date	2022-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197482-8
ISSN	1552-3365 ; 0363-5465
ISSN (online)	1552-3365
ISSN	0363-5465
DOI	10.1177/03635465221118580
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Article ; Online: (4-Aminopyridine)-PLGA-PEG as a Novel Thermosensitive and Locally Injectable Treatment for Acute Peripheral Nerve Injury.

Manto, Kristen M / Govindappa, Prem Kumar / Parisi, Daniele / Karuman, Zara / Martinazzi, Brandon / Hegarty, John P / Talukder, M A Hassan / Elfar, John C

ACS applied bio materials

2021 Volume 4, Issue 5, Page(s) 4140–4151

Abstract: Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective ... ...

Abstract	Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4-aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)-poly(lactide-
MeSH term(s)	4-Aminopyridine/administration & dosage ; 4-Aminopyridine/therapeutic use ; Acute Disease ; Animals ; Biocompatible Materials/administration & dosage ; Biocompatible Materials/chemical synthesis ; Biocompatible Materials/therapeutic use ; Disease Models, Animal ; Male ; Materials Testing ; Mice ; Mice, Inbred C57BL ; Molecular Structure ; Particle Size ; Peripheral Nerve Injuries/drug therapy ; Polyesters/administration & dosage ; Polyesters/therapeutic use ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/therapeutic use ; Temperature
Chemical Substances	Biocompatible Materials ; Polyesters ; polyethylene glycol-poly(lactide-co-glycolide) ; Polyethylene Glycols (3WJQ0SDW1A) ; 4-Aminopyridine (BH3B64OKL9)
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.0c01566
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Article ; Online: 4-Aminopyridine: A Single-Dose Diagnostic Agent to Differentiate Axonal Continuity in Nerve Injuries.

Gurjar, Anagha A / Manto, Kristen M / Estrada, Juan A / Kaufman, Marc / Sun, Dongxiao / Talukder, M A Hassan / Elfar, John C

Military medicine

2021 Volume 186, Issue Suppl 1, Page(s) 479–485

Abstract: Introduction: Traumatic peripheral nerve injuries (TPNIs) are increasingly prevalent in battlefield trauma, and the functional recovery with TPNIs depends on axonal continuity. Although the physical examination is the main tool for clinical diagnosis ... ...

Abstract	Introduction: Traumatic peripheral nerve injuries (TPNIs) are increasingly prevalent in battlefield trauma, and the functional recovery with TPNIs depends on axonal continuity. Although the physical examination is the main tool for clinical diagnosis with diagnostic work up, there is no diagnostic tool available to differentiate nerve injuries based on axonal continuity. Therefore, treatment often relies on "watchful waiting," and this leads to muscle weakness and further reduces the chances of functional recovery. 4-aminopyridine (4-AP) is clinically used in multiple sclerosis patients for walking performance improvement. Preliminary results in conscious mice suggested a diagnostic role of 4-AP in distinguishing axonal continuity. In this study, we thought to evaluate the diagnostic potential of 4-AP on the axonal continuity in unawake/sedated animals. Materials and methods: Rat sciatic nerve crush and transection injuries were used in this study. Briefly, rats were anesthetized with isoflurane and mechanically ventilated with oxygen-balanced vaporized isoflurane. Sciatic nerve and triceps surae muscles were exposed by blunt dissection, and a stimulating electrode was placed under a sciatic nerve proximal to the crush injury. A force transducer measured muscle tension response to electrical stimulation of sciatic nerve. Muscle response was measured before crush, after crush, and 30 minutes after systemic 4-AP (150 µg/kg) or local (4-AP)-poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG) treatment. Results: We found that both crush and transection injuries in sciatic nerve completely abolished muscle response to electrical stimulation. Single dose of systemic 4-AP and local (4-AP)-PLGA-PEG treatment with crush injury significantly restored muscle responses to electrical stimulation after 30 minutes of administration. However, systemic 4-AP treatment had no effect on muscle response after nerve transection. These results clearly demonstrate that 4-AP can restore nerve conduction and produce muscle response within minutes of administration only when there is a nerve continuity, even in the sedated animal. Conclusions: We conclude that 4-AP could be a promising diagnostic agent in differentiating TPNI based on axonal continuity.
MeSH term(s)	4-Aminopyridine/pharmacology ; 4-Aminopyridine/therapeutic use ; Animals ; Axons ; Male ; Mice ; Peripheral Nerve Injuries/diagnosis ; Peripheral Nerve Injuries/drug therapy ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Sciatic Nerve
Chemical Substances	4-Aminopyridine (BH3B64OKL9)
Language	English
Publishing date	2021-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usaa310
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Article: Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice: effects of 4-aminopyridine.

Lee, Jung Il / Talukder, M A Hassan / Karuman, Zara / Gurjar, Anagha A / Govindappa, Prem Kumar / Guddadarangaiah, Jagadeeshaprasad M / Manto, Kristen M / Wandling, Grant D / Hegarty, John P / Waning, David L / Elfar, John C

Neural regeneration research

2022 Volume 18, Issue 2, Page(s) 439–444

Abstract: We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve ... ...

Abstract	We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve transection, gap, and grafting models. To evaluate and compare the functional recovery, nerve morphology, and muscle atrophy, we used a novel stepwise nerve transection with gluing (STG), as well as 7-mm irreparable nerve gap (G-7/0) and 7-mm isografting in 5-mm gap (G-5/7) models in the absence and presence of 4-AP treatment. Following surgery, sciatic functional index was determined weekly to evaluate the direct in vivo global motor functional recovery. After 12 weeks, nerves were processed for whole-mount immunofluorescence imaging, and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber cross-sectional area and minimal Feret's diameter. Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model. 4-AP did not affect the sciatic functional index recovery in any model. Compared to STG, nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting. While muscle weight, cross-sectional area, and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7, 4-AP treatment significantly increased right TA muscle mass, cross-sectional area, and minimal Feret's diameter in G-7/0 model. These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap, and 4-AP exerts differential effects on functional recovery and muscle atrophy.
Language	English
Publishing date	2022-08-24
Publishing country	India
Document type	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.346456
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Article ; Online: Altered gut microbiota composition with antibiotic treatment impairs functional recovery after traumatic peripheral nerve crush injury in mice: effects of probiotics with butyrate producing bacteria.

Rodenhouse, Andrew / Talukder, M A Hassan / Lee, Jung Il / Govindappa, Prem Kumar / O'Brien, Mary / Manto, Kristen M / Lloyd, Kelsey / Wandling, Grant D / Wright, Justin R / Chen See, Jeremy R / Anderson, Samantha L / Lamendella, Regina / Hegarty, John P / Elfar, John C

BMC research notes

2022 Volume 15, Issue 1, Page(s) 80

Abstract: Objective: Antibiotics (ABX) are widely used for life-threatening infections and also for routine surgical operations. Compelling evidence suggests that ABX-induced alterations of gut microbiota composition, termed dysbiosis, are linked with diverse ... ...

Abstract	Objective: Antibiotics (ABX) are widely used for life-threatening infections and also for routine surgical operations. Compelling evidence suggests that ABX-induced alterations of gut microbiota composition, termed dysbiosis, are linked with diverse disease states including neurological and neurodegenerative conditions. To combat the consequences of dysbiosis, probiotics (PBX) are widely used. ABX-induced dysbiosis is reported to impair neurological function after spinal cord injury. Traumatic peripheral nerve injury (TPNI) results in profound neurologic impairment and permanent disability. It is unknown whether ABX treatment-induced dysbiosis has any impact on TPNI-induced functional recovery, and if so, what role medical-grade PBX could have on TPNI recovery. Results: In this study, ABX-induced dysbiosis and PBX-induced microbiota enrichment models were used to explore the potential role of gut microbiome in TPNI. Stool analysis with 16S ribosomal RNA (rRNA) gene sequencing confirmed ABX-induced dysbiosis and revealed that ABX-induced changes could be partially restored by PBX administration with an abundance of butyrate producing bacteria. Pre-injury ABX significantly impaired, but pre-injury PBX significantly improved post-TPNI functional recovery. Importantly, post-injury PBX protected against pre-injury ABX-induced functional impairment. These findings demonstrate that reestablishment of gut microbiota composition with butyrate producing PBX during ABX-induced dysbiosis could be a useful adjuvant therapy for TPNI.
MeSH term(s)	Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria, Anaerobic ; Butyrates/pharmacology ; Crush Injuries/drug therapy ; Gastrointestinal Microbiome ; Mice ; Peripheral Nerve Injuries ; Peripheral Nerves ; Probiotics ; RNA, Ribosomal, 16S/genetics
Chemical Substances	Anti-Bacterial Agents ; Butyrates ; RNA, Ribosomal, 16S
Language	English
Publishing date	2022-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-022-05967-8
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