scholarly journals Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury

2019 ◽  
Vol 20 (3) ◽  
pp. 502 ◽  
Author(s):  
Buyandelger Batsaikhan ◽  
Jing-Ya Wang ◽  
Michael Scerba ◽  
David Tweedie ◽  
Nigel Greig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Neuronal Degeneration ◽  
Neurological Deficits ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Tnf Α

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.

scholarly journals Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

2021 ◽  
Author(s):  
Changmeng Cui ◽  
Changshui Wang ◽  
Feng Jin ◽  
Mengqi Yang ◽  
Lingsheng Kong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Vitamin D ◽  
Brain Injury ◽  
Neurological Deficits ◽  
Autophagic Flux ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Nrf2 Activation ◽  
Autophagic Process

Abstract Background: Traumatic brain injury (TBI) initiates an oxidative cascade that contributes to the delayed progressive damage, whereas autophagy is critical in maintaining homeostasis during stressful challenge. We previously demonstrated that vitamin D (VitD) shows strong neuroprotective and anti-oxidative properties in the animal models of TBI. Therefore, the present study aimed to further explore the potential interrelationship between oxidative stress and autophagy in the progression of TBI and therapeutic mechanism of VitD. Methods: Neuroprotective effects of calcitriol, the active form of VitD, were examined following TBI. We further evaluated the impacts of TBI and VitD treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling. To confirm the mechanism, chloroquine (CQ) treatment and Nrf2−/− mice were used to block autophagy and Nrf2 pathway, respectively. Results: We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. To further confirm whether autophagy was responsible for Keap1 degradation and Nrf2 activation, the lysosomal inhibitor, CQ, was used to block autophagy. Our data suggested that CQ treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of VitD against both TBI-induced neurological deficits and neuronal apoptosis. Conclusions: Therefore, our work demonstrated a neuroprotective role of VitD in TBI by triggering Nrf2 activation, which might be mediated by autophagy.

scholarly journals Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

2021 ◽  
Author(s):  
Changmeng Cui ◽  
Changshui Wang ◽  
Feng Jin ◽  
Mengqi Yang ◽  
Lingsheng Kong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Vitamin D ◽  
Brain Injury ◽  
Neurological Deficits ◽  
Autophagic Flux ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Nrf2 Activation ◽  
Autophagic Process

Abstract Background: Traumatic brain injury (TBI) initiates an oxidative cascade that contributes to the delayed progressive damage, whereas autophagy is critical in maintaining homeostasis during stressful challenge. We previously demonstrated that vitamin D (VitD) shows strong neuroprotective and anti-oxidative properties in the animal models of TBI. Therefore, the present study aimed to further explore the potential interrelationship between oxidative stress and autophagy in the progression of TBI and therapeutic mechanism of VitD. Methods: Neuroprotective effects of calcitriol, the active form of VitD, were examined following TBI. We further evaluated the impacts of TBI and VitD treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling. To confirm the mechanism, chloroquine (CQ) treatment and Nrf2 −/− mice were used to block autophagy and Nrf2 pathway, respectively. Results: We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. To further confirm whether autophagy was responsible for Keap1 degradation and Nrf2 activation, the lysosomal inhibitor, CQ, was used to block autophagy. Our data suggested that CQ treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of VitD against both TBI-induced neurological deficits and neuronal apoptosis. Conclusions: Therefore, our work demonstrated a neuroprotective role of VitD in TBI by triggering Nrf2 activation, which might be mediated by autophagy.

scholarly journals Calcitriol confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Changmeng Cui ◽  
Changshui Wang ◽  
Feng Jin ◽  
Mengqi Yang ◽  
Lingsheng Kong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Active Form ◽  
Neurological Deficits ◽  
Autophagic Flux ◽  
Related Factor ◽  
Neuroprotective Effects ◽  
Nrf2 Activation ◽  
Autophagic Process

Abstract Background The present study aimed to further explore the potential interaction between oxidative stress and autophagy in the progression of traumatic brain injury (TBI) and therapeutic mechanism of calcitriol, the active form of vitamin D (VitD). Methods Neuroprotective effects of calcitriol were examined following TBI. We further evaluated the impacts of TBI and calcitriol treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling. Results We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. In support, we further found that chloroquine (CQ) treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of calcitriol against both TBI-induced neurological deficits and neuronal apoptosis. Conclusions Therefore, our work demonstrated a neuroprotective role of calcitriol in TBI by triggering Nrf2 activation, which might be mediated by autophagy.

scholarly journals Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xiao Hu ◽  
Shirong Li ◽  
Desislava Met Doycheva ◽  
Lei Huang ◽  
Cameron Lenahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Neuronal Degeneration ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Artery Ligation ◽  
Neuroprotective Effects

Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.

scholarly journals A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

2017 ◽  
Vol 38 (10) ◽  
pp. 1818-1827 ◽  
Author(s):  
Raghavendar Chandran ◽  
TaeHee Kim ◽  
Suresh L Mehta ◽  
Eshwar Udho ◽  
Vishal Chanana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Function ◽  
Neurological Dysfunction ◽  
Vehicle Group ◽  
Lesion Volume ◽  
Post Injury ◽  
Cortical Contusion ◽  
Nrf2 Activator

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS formation and potentiates ROS disposal concurrently is efficacious after TBI.

scholarly journals Administration of a 20-Hydroxyeicosatetraenoic Acid Synthesis Inhibitor Improves Outcome in a Rat Model of Pediatric Traumatic Brain Injury

2019 ◽  
Vol 41 (3-4) ◽  
pp. 166-176 ◽  
Author(s):  
Shiyu Shu ◽  
Zhi Zhang ◽  
Dawn Spicer ◽  
Ewa Kulikowicz ◽  
Ke Hu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ischemia Reperfusion ◽  
Memory Task ◽  
Male Rats ◽  
Lesion Volume ◽  
Hydroxyeicosatetraenoic Acid ◽  
Post Injury ◽  
Synthesis Inhibitor ◽  
Tnf Α

The arachidonic acid pathway metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemia/reperfusion brain injury. Inhibition of 20-HETE formation can protect the developing brain from global ischemia. Here, we examined whether treatment with the 20-HETE synthesis inhibitor N-hydroxy-N-4-butyl-2-methylphenylformamidine (HET0016) can protect the immature brain from traumatic brain injury (TBI). Male rats at postnatal day 9–10 underwent controlled cortical impact followed by intraperitoneal injection with vehicle or HET0016 (1 mg/kg, 5 min and 3 h post-injury). HET0016 decreased the lesion volume by over 50% at 3 days of recovery, and this effect persisted at 30 days as the brain matured. HET0016 decreased peri-lesion gene expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]) at 1 day and increased reparative cytokine (IL-4, IL-10) expression at 3 days. It also partially preserved microglial ramified processes, consistent with less activation. HET0016 decreased contralateral hindlimb foot faults and improved outcome on the novel object recognition memory task 30 days after TBI. In cultured BV2 microglia, HET0016 attenuated the lipopolysaccharide-evoked increase in release of TNF-α. Our data show that HET0016 improves acute and long-term histologic and functional outcomes, in association with an attenuated neuroinflammatory response after contusion of an immature rat brain.

scholarly journals Lack of mitochondrial ferritin aggravated neurological deficits via enhancing oxidative stress in a traumatic brain injury murine model

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Ligang Wang ◽  
Libo Wang ◽  
Zhibo Dai ◽  
Pei Wu ◽  
Huaizhang Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Knockout Mice ◽  
Brain Injuries ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Important Correlation ◽  
The Brain ◽  
And Oxidative Stress

Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.

scholarly journals Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

2020 ◽  
Author(s):  
Han Wang ◽  
Xiaoming Zhou ◽  
Lingyun Wu ◽  
Guangjie Liu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Neurons ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Related Factor ◽  
Mice Model ◽  
Anti Inflammatory

Abstract Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au.Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

scholarly journals Neuroprotective Effects of Tempol, a Catalytic Scavenger of Peroxynitrite-Derived Free Radicals, in a Mouse Traumatic Brain Injury Model

2008 ◽  
Vol 28 (6) ◽  
pp. 1114-1126 ◽  
Author(s):  
Ying Deng-Bryant ◽  
Indrapal N Singh ◽  
Kimberly M Carrico ◽  
Edward D Hall
Keyword(s):  
Traumatic Brain Injury ◽  
Free Radicals ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Complete Suppression ◽  
Post Injury ◽  
Multiple Dosing ◽  
Neuroprotective Effects

We examined the ability of tempol, a catalytic scavenger of peroxynitrite (PN)-derived free radicals, to reduce cortical oxidative damage, mitochondrial dysfunction, calpain-mediated cytoskeletal (α-spectrin) degradation, and neurodegeneration, and to improve behavioral recovery after a severe (depth 1.0 mm), unilateral controlled cortical impact traumatic brain injury (CCI-TBI) in male CF-1 mice. Administration of a single 300 mg/kg intraperitoneal dose of tempol 15 mins after TBI produced a complete suppression of PN-mediated oxidative damage (3-nitrotyrosine, 3NT) in injured cortical tissue at 1 h after injury. Identical tempol dosing maintained respiratory function and attenuated 3NT in isolated cortical mitochondria at 12 h after injury, the peak of mitochondrial dysfunction. Multiple dosing with tempol (300 mg/kg intraperitoneally at 15 mins, 3, 6, 9, and 12 h) also suppressed α-spectrin degradation by 45% at its 24 h post-injury peak. The same dosing regimen improved 48 h motor function and produced a significant, but limited (17.4%, P<0.05), decrease in hemispheric neurodegeneration at 7 days. These results are consistent with a mechanistic link between PN-mediated oxidative damage to brain mitochondria, calpain-mediated proteolytic damage, and neurodegeneration. However, the modest neuroprotective effect of tempol suggests that multitarget combination strategies may be needed to interfere with posttraumatic secondary injury to a degree worthy of clinical translation.

scholarly journals Lactobacillus acidophilus Exerts Neuroprotective Effects in Mice with Traumatic Brain Injury

2019 ◽  
Vol 149 (9) ◽  
pp. 1543-1552 ◽  
Author(s):  
Yuanyuan Ma ◽  
Tianyao Liu ◽  
Jingjing Fu ◽  
Shaoli Fu ◽  
Chen Hu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gut Microbiota ◽  
Lactobacillus Acidophilus ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Microbiota Composition ◽  
Neuroprotective Effects ◽  
Tnf Α ◽  
Underlying Mechanisms

ABSTRACT Background Traumatic brain injury (TBI) causes dysbiosis and intestinal barrier disruption, which further exacerbate brain damage via an inflammatory pathway. Gut microbiota remodeling by Lactobacillus acidophilus (LA) is a potential intervention. Objective The aim of this study was to investigate the neuroprotective effects of LA in TBI and elucidated underlying mechanisms. Methods C57BL/6 male mice (aged 8–9 wk) were subjected to weight-drop impact and gavaged with saline (TBI + vehicle) or LA (1 × 1010 CFU) (TBI + LA) on the day of injury and each day after for 1, 3, or 7 d. The sham + vehicle mice underwent craniotomy without brain injury and were gavaged with saline. Sensorimotor functions were determined pre-TBI and 1, 3, and 7 d postinjury. Indexes of neuroinflammation, peripheral inflammation, and intestinal barrier function were measured on days 3 and 7. Microbiota composition was measured 3 d postinjury. The data were mainly analyzed by 2-factor ANOVA. Results Compared with sham + vehicle mice, the TBI + vehicle mice exhibited impairments in the neurological severity score (+692%, day 3; +600%, day 7) and rotarod test (−58%, day 3; −45%, day 7) (P < 0.05), which were rescued by LA. The numbers of microglia (total and activated) and astrocytes and concentrations of TNF-α and IL1-β in the perilesional cortex were elevated in the TBI + vehicle mice on day 3 or 7 compared with sham + vehicle mice (P < 0.05) and were normalized by LA. Compared with sham + vehicle mice, the TBI + vehicle mice exhibited increased serum concentrations of endotoxin and TNF-α, and intestinal barrier permeability (D-lactate) on days 3 and 7 (P < 0.05), and these changes were alleviated by LA. Three days postinjury, the microbiota composition was disrupted in the TBI + vehicle mice compared with sham + vehicle mice (P < 0.05), which was restored by LA. Conclusion Our results demonstrate that LA exerts neuroprotective effects that may be associated with gut microbiota remodeling in TBI mice.

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