Traumatic Brain Injury In Rats Research Articles

Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway.

Phosphodiesterase 10A (PDE10A) is a dual-substrate phosphodiesterase that is highly expressed in the striatal complex. PDE10A is an important target for the treatment of ganglion dysfunction and neuroinflammation-related diseases, but its possible impact on traumatic brain injury (TBI) is still unclear. This study aims to investigate the protective effects of inhibiting PDE10A on neuroinflammation post-TBI injury and its possible molecular mechanism. The expression of PDE10A in rats and HT22 cells was determined by Western blotting. The neurological dysfunction of these rats was detected by Nissl staining, hematoxylin-eosin (HE) staining, and Morris water maze test. The activity of HT22 cells was measured by MTT. The findings of this study suggest that PDE10A is highly expressed in the brain tissue of TBI rats and HT22 cells induced by mechanical injury. Inhibition of PDE10A reduces the expression of interleukin-1β (IL-1β) and interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in HT22 cells induced by mechanical injury to inhibit cell apoptosis. Simultaneously, inhibition of PDE10A in TBI rats reduces the time to find a visible platform in the same pool, while cAMP/PKA activator treatment alleviates all of the abovementioned phenomena. Additionally, it is further confirmed that inhibition of PDE10A activates the cAMP/PKA pathway and downregulates the expression of NRLP3. These findings demonstrate that inhibition of PDE10A exerts neuroprotection by inhibiting apoptosis and inflammation following TBI, at least partially by the cAMP/PKA/NLRP3 pathway.

Nonoxid-HMGB1 Attenuates Cognitive Impairment After Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) is a major global burden of health. As an accepted inflammatory mediator, high mobility group box 1 (HMGB1) is found to be effective in facilitating neurogenesis and axonal regeneration. SH3RF2 (also known as POSHER), an E3 ligase SH3 domain-containing ring finger 2, belongs to the SH3RF family of proteins. Here, we aimed to investigate the role of redox states of HMGB1 on neurite outgrowth and regeneration both in vitro and in vivo. In this study, distinct recombinant HMGB1 redox isoforms were used. Sequencing for RNA-seq and data analysis were performed to find the potential downstream target of nonoxid-HMGB1 (3S-HMGB1). Protein changes and distribution of SH3RF2 were evaluated by western blot assays and immunofluorescence. Lentivirus and adeno-associated virus were used to regulate the expression of genes. Nonoxid-HMGB1-enriched exosomes were constructed and used to treat TBI rats. Neurological function was evaluated by OF test and NOR test. Results demonstrated that nonoxid-HMGB1 and fr-HMGB1, but not ds-HMGB1, promoted neurite outgrowth and axon elongation. RNA-seq and western blot assay indicated a significant increase of SH3RF2 in neurons after treated with nonoxid-HMGB1 or fr-HMGB1. Notably, the beneficial effects of nonoxid-HMGB1 were attenuated by downregulation of SH3RF2. Furthermore, nonoxid-HMGB1 ameliorated cognitive impairment in rats post-TBI via SH3RF2. Altogether, our experimental results suggest that one of the promoting neurite outgrowth and regeneration mechanisms of nonoxid-HMGB1 is mediated through the upregulated expression of SH3RF2. Nonoxid-HMGB1 is an attractive therapeutic candidate for the treatment of TBI.

Plasma Lipid Profiles Change with Increasing Numbers of Mild Traumatic Brain Injuries in Rats.

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses.

IDF21-0041 Hyperglycemia aggravates apoptosis and neuroinflammation at the intermediate stage after post-traumatic brain injury

Background: Traumatic brain injury (TBI) is a highly lethal event with a poor prognosis. Recovering residual neuronal function in the intermediate stage of TBI is important for treatment; however, neuroinflammation and neuronal apoptosis impede residual neuronal repair processes. Hyperglycemia influences inflammatory processes and neuronal survival. Aim: We explored the effects of high glucose on neuroinflammation and neuronal death during the intermediate phase of TBI. Method: Rat models of type 2 diabetes mellitus and/or TBI were developed and behaviorally assessed. The histopathological changes were detected by Hematoxylin and eosin staining. Proinflammatory and anti-inflammatory in serum and hippocampal tissue were tested. And neural apoptosis was observed by Tunel staining and the expression of cleaved caspase-3 (CC-3) protein and Bax/Bcl-2 ratio were recorded. In in vitro assays, levels of inflammatory factors and apoptosis associated proteins were measured after MEK5 activation. Immunofluorescence colocalization of neuron-specific nuclear protein and p-MEK5 was analyzed by immunofluorescence cytochemistry. Results: Neurological function and cognitive abilities were impaired in TBI rats and worsened by type 2 diabetes mellitus. Histopathological staining and analyses of serum and hippocampal mRNA and protein levels indicated that neuroinflammation and apoptosis were induced in TBI rats and exacerbated by hyperglycemia. Hyperglycemia inhibited hippocampal MEK5 phosphorylation in TBI rats. In vitro assays were used to assess inflammatory factor expression, apoptotic protein levels and neuronal survival after MEK5 activation in TBI- and/or high-glucose-treated neurons. MEK5/extracellular signal-regulated kinase 5 (ERK5) pathway activation reduced the inflammation, cleaved caspase-3 expression, Bax/Bcl-2 ratio and apoptosis of TBI neurons, even under high-glucose conditions. Discussion: Our results indicated that HG exacerbated hippocampal injury and exaggerated the neurological deficits and learning/memory problems after TBI. We observed that HG aggravated neuroinflammation partly by inhibiting the MEK5/ERK5 signaling pathway. In addition to activating inflammation, HG has been reported to reduce neuronal survival by upregulating CC-3 and disrupting the balance between Bax and Bcl-2. The pro-apoptotic effects of HG have frequently been observed in individuals exposed to prolonged hyperglycemia. ERK5 was found to inhibit endoplasmic reticulum stress and apoptosis in pancreatic β-cells, thereby ameliorating the tissue damage caused by hyperglycemia. In the present study, activation of MEK5/ERK5 may reduced TBI cauded neuronal apoptosis. In conclusion, HG exacerbated hippocampal injury after TBI, largely by disrupting the homeostasis of pro- and anti-inflammatory cytokines and inducing hippocampal neuronal apoptosis. The MEK5/ERK5 pathway participated in both of these processes. These experimental findings emphasize the importance of good glycemic control for the functional recovery of residual neurons in TBI patients.

Gastrodin suppresses pyroptosis and exerts neuroprotective effect in traumatic brain injury model by inhibiting NLRP3 inflammasome signaling pathway.

Traumatic brain injury (TBI), also known as head injury or brain injury, refers to the head injury caused by mechanical impact. It is necessary to develop effective new therapies for TBI injury. Gastrodin (GAS) is the main bioactive ingredient from the rhizome of Gastrodia elata and has significant therapeutic effect on nervous system diseases. However, the protective effects of GAS on brain tissue and related regulatory mechanism in traumatic brain injury remain elusive. Herein, we explored the role of GAS in traumatic brain injury and its related mechanism. We found Gastrodin reduced brain tissue injury and improved functional recovery of injury nerve in TBI rats, and alleviated inflammation. Gastrodin decreased the level of pyroptosis in brain tissue of TBI rats. Further, we found GAS suppressed NLRP3 inflammasome signaling pathway, and therefore suppressed pyroptosis and exerted neuroprotective effect. GAS could serve as a promising drug for TBI treatment.

P2X4 Inhibition reduces microglia inflammation and apoptosis by NLRP3 and improves nervous system defects in rat brain trauma model

The purinergic receptor P2X4 is an adenosine triphosphate (ATP)-gated cation channel, which plays an essential role in regulating various biological activities in the organism. This study was designed to investigate the potential role and mechanism of P2X4 in the traumatic brain injury (TBI) rat model. Real-time PCR, Western blot, immunofluorescence, apoptosis, brain water content and neurological score analysis were evaluated. We found that the expression level of P2X4 surrounding the injured area of the brain in the TBI rat model increased significantly after 48 h. Following the P2X4 selective antagonist 5-BDBD treatment, the neurological damage after TBI was significantly improved and brain edema was reduced. The inhibition of P2X4 effectively reduced the inflammation and apoptosis of microglia, and NLRP3 may be involved in this process. Our results indicate that inhibition of P2X4 may be a potential therapeutic approach for TBI by reducing the occurrence of inflammation and apoptosis of microglia, alleviating brain edema, and improving neurological deficits.

Statement of Retraction: Downregulated lncRNA CRNDE contributes to the enhancement of nerve repair after traumatic brain injury in rats

This article refers to:RETRACTED ARTICLE: Downregulated lncRNA CRNDE contributes to the enhancement of nerve repair after traumatic brain injury in rats

Poly d,l-(lactic-co-glycolic) Acid PEGylated Isoliquiritigenin Alleviates Traumatic Brain Injury by Reversing Cyclooxygenase 2 Level.

As a severe neurological disease of trauma, traumatic brain injury (TBI) leads to other disorders, such as depression, dementia and epilepsy. This study investigated whether poly d,l-(lactic-co-glycolic) acid (PLGA) PEGylated isoliquiritigenin could alleviate TBI. One hundred and eighty-three patients with clinical brain trauma were divided into two groups with or without intracranial injury in magnetic resonance imaging. The clinical results showed that serum cyclooxygenase 2 (COX-2) levels were obviously increased in the TBI patients compared to the patients with head trauma only or healthy individuals. Intracranial injection of isoliquiritigenin in TBI rats reversed TBI induced increase of COX-2 level, significantly reduced water content and contusion volume. Our findings suggest that PLGA PEG nanoparticles loaded with isoliquiritigenin can achieve the same effects as intracranial administration of isoliquiritigenin in reducing serum COX-2 level.

Lu Tong Ke Li protects neurons from injury by regulating inflammation in rats with brain trauma.

Currently, there is no effective therapy for traumatic brain injury (TBI). Therefore, this study was conducted to determine the protective effect of Lu Tong Ke Li (LTKL), a Chinese medicine, for TBI in experimental animals. The TBI rat model was induced using the modified Feeney's protocol. The rats were divided into four groups: Sham group, Control group, LTKL lower-dose group (LTL, 2 g/kg/day, p.o.), and LTKL higher-dose group (LTH, 4 g/kg/day, p.o.). The Neurological Severity Score (NSS) was used to examine neurological function. Magnetic resonance imaging was performed to check the brain tissue lesions in rats. Cell apoptosis in the damaged area was evaluated using the Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling assay. Reverse-transcription polymerase chain reaction was used to investigate the expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin 10 (IL-10). The TBI rat model was successfully constructed. Neurological function was enhanced at 14, 21, and 28 days post TBI in the LTH groups, indicated by gradually decreased NSS scores. Administration of LTH led to fewer brain defects in the damaged area, and the number of apoptosis cells in the brain injury area markedly decreased. LTKL treatment led to upregulation of IL-10 expression and downregulation of TNF-α and IL-1β expressions at the molecular level. LTKL can improve the neurobehavior of TBI. The neuroprotective effect was probably related to regulation of inflammation cytokines. Our results provide crucial evidence of the potentially useful application of LTKL in the therapy of TBI in clinic practice in the future.

Therapeutic efficacy of rolipram delivered by PgP nanocarrier on secondary injury and motor function in a rat TBI model.

Aim: To develop poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) as a nanocarrier for the delivery of rolipram (Rm) and evaluate the therapeutic efficacy of Rm-loaded PgP (Rm-PgP) on secondary injury and motor function in a rat traumatic brain injury (TBI) model. Materials& methods: Rm-PgP was injected in the injured brain lesion immediately after TBI using a microinjection pump. Secondary injury pathologies such as inflammatory response, apoptosis and astrogliosis were assessed by histological analysis and functional recovery was assessed by assorted motor function tests. Results: Rm-PgP restored cyclic adenosine monophosphate level in the injured brain close to the sham level and Rm-PgP treatment reduced lesion volume, neuroinflammation and apoptosis and improved motor function at 7days post-TBI. Conclusion: One single injection of Rm-PgP can be effective for acute mild TBI treatment.

Neuroprotective effects of lentivirus‐mediated aquaporin‐4 gene silencing in rat model of traumatic brain injury

ABSTRACT Background Traumatic brain injury (TBI) is a common clinical condition caused by external force. Aquaporin-4 (AQP4) in astrocytes participates in the generation of cell swelling in TBI. Methods This research explored the effect of AQP4 gene silencing in a TBI rat model. A hydraulic craniocerebral trauma instrument was employed for establishing the TBI rat model. AQP4 expression in the brain was inhibited by the injection of AQP4 shRNA-lentiviral vector. The expression of relative genes was evaluated by Western blot and qRT-PCR. Neuronal apoptosis was analyzed by TUNEL assay. Results AQP4 shRNA treatment inhibited AQP4 expression in the brain of rats with TBI. AQP4 shRNA alleviated TBI-induced brain edema and neurological deficit in rats. Neuronal apoptosis and astrocyte activation in TBI rats were reduced by AQP4 silencing. Conclusion This research demonstrated that AQP4 shRNA-induced silencing of AQP4 in the TBI rat model reduced the expression of AQP4 and GFAP, alleviated brain edema, neurological deficit, neuronal apoptosis and inhibited astrocyte activation.

Protective role of wogonin following traumaticbrain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway.

Traumatic brain injury (TBI) is usually caused by accidental injuries and traffic accidents, with a very high mortality rate. Treatment and management following TBI are essential to reduce patient injury and help improve long-term prognosis. Wogonin is a flavonoid compound with an antioxidant effect extracted from Scutellaria baicalensis Georgi. However, the function and mechanism of wogonin in protecting brain injury remain to be elucidated. The present study established a TBI model of Sprague-Dawley rats and treated them with wogonin following trauma. The results showed that wogonin treatment significantly reduced neurobehavioral disorders, brain edema and hippocampal neuron damage caused by TBI. It was found that in TBI rats, administration of wogonin increased the levels of antioxidant factors glutathione, superoxide dismutase and catalase in the CA1 region of the hippocampus and significantly inhibited the production of malondialdehyde and reactive oxygen species. western blotting data showed that wogonin exerted antioxidant activity by downregulating the level of NOX2 protein. In inhibiting cell apoptosis, wogonin upregulated the expression of Bcl-2 protein in the hippocampal CA1 region of TBI rats and inhibited caspase-3 and Bax proteins. Additionally, wogonin inhibited the progression of injury following TBI through the PI3K/Akt/nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Wogonin increased the expression of phosphorylated Akt, Nrf2 and HO-1 in the hippocampus of TBI rats. Following the administration of PI3K inhibitor LY294002, the upregulation of these proteins by wogonin was partly reversed. In addition, LY294002 partially reversed the regulation of wogonin on NOX2, caspase-3, Bax and Bcl-2 proteins. Therefore, wogonin exerts antioxidant and anti-apoptotic properties to prevent hippocampal damage following TBI, which is accomplished through the PI3K/Akt/Nrf2/HO-1 pathway.

The effect of clopidogrel and aspirin on the severity of traumatic brain injury in a rat model

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Aspirin (ASA) and clopidogrel (CLOP) are antiplatelet agents that inhibit platelet aggregation. They are implicated in worsening the intracerebral haemorrhage (ICH) risk post-TBI. However, antiplatelet drugs may also exert a neuroprotective effect post-injury. We determined the impact of ASA and CLOP treatment, alone or in combination, on ICH and brain damage in an experimental rat TBI model. We assessed changes in platelet aggregation and measured serum thromboxane by enzyme immune assay. We also explored a panel of brain damage and apoptosis biomarkers by immunoblotting. Rats were treated with ASA and/or CLOP for 48 h prior to TBI and sacrificed 48 h post-injury. In rats treated with antiplatelet agents prior to TBI, platelet aggregation was completely inhibited, and serum thromboxane was significantly decreased, compared to the TBI group without treatment. TBI increases UCHL-1 and GFAP, but decreases hexokinase expression compared to the non-injured controls. All groups treated with antiplatelet drugs prior to TBI had decreased UCH-L1 and GFAP serum levels compared to the TBI untreated group. Furthermore, the ASA and CLOP single treatments increased the hexokinase serum levels. We confirmed that αII-spectrin cleavage increased post-TBI, with the highest cleavage detected in CLOP-treated rats. Aspirin and/or CLOP treatment prior to TBI is a double-edged sword that exerts a dual effect post-injury. On one hand, ASA and CLOP single treatments increase the post-TBI ICH risk, with a further detrimental effect from the ASA + CLOP treatment. On the other hand, ASA and/or CLOP treatments are neuroprotective and result in a favourable profile of TBI injury markers. The ICH risk and the neuroprotection benefits from antiplatelet therapy should be weighed against each other to ameliorate the management of TBI patients.

Characteristics of Epileptiform Spike-wave Discharges and Chronic Histopathology in Controlled Cortical Impact Model of Sprague-Dawley Rats.

Post-traumatic epilepsy (PTE) is a serious complication that can occur following traumatic brain injury (TBI). Sustained secondary changes after TBI promote the process of PTE. Here, we aim to evaluate changes in behavior, electrocorticogram, and histomorphology in rats following chronic TBI models. We observed intensive 7-8Hz spike-wave-discharges (SWDs) at frontal recording sites and quantified them in SD rats with different degrees of TBI and compared them with age-matched sham rats to evaluate the association between SWDs and injury severity. Notably, although SWDs were even presented in the sham group, the number and duration of events were much lower than those in the TBI groups. SWDs have numerous similarities to absence seizures, such as abrupt onset, termination, and lack of postictal suppression, which may be the nonconvulsive characteristics of PTE. Retigabine, a novel antiepileptic drug, is ineffective in reducing SWDs. In addition, we examined chronic histopathological changes in TBI rats. Rats subjected to moderate and severe TBI exhibited significantly impaired neurological function, which was accompanied by marked cortical injury, hippocampus deformation, reactive gliosis, and mossy fiber sprouting. Long-term progressive structural changes in the brain are one of the characteristics of epileptogenesis after TBI. Our study provided the potential value of epileptiform SWDs in reflecting the nonconvulsive characteristic of PTE and highlighted the vital role of chronic pathological changes, such as reactive gliosis, in promoting the epileptogenesis following TBI.

Polydatin improves intestinal barrier injury after traumatic brain injury in rats by reducing oxidative stress and inflammatory response via activating SIRT1-mediated deacetylation of SOD2 and HMGB1

To investigate the protective effect against intestinal mucosal injury in rats following traumatic brain injury (TBI) and explore the underlying mechanism. SD rat models of TBI were established by fluid percussion injury (FPI), and the specimens were collected at 12, 24, 48, and 72 h after TBI. Another 15 rats were randomly divided into shamoperated group (n=5), TBI with saline treatment (TBI+NS) group (n=5), and TBI with PD treatment (TBI+PD) group (treated with 30 mg/kg PD after TBI; n=5). Body weight gain and fecal water content of the rats were recorded, and after the treatments, the histopathology of the jejunum was observed, and the levels of D-lactic acid (D-LAC), diamine oxidase (DAO), ZO-1, claudin-5, and reactive oxygen species (ROS) were detected. Lipid peroxide (LPO) and superoxide dismutase (SOD) 2 content, jejunal pro-inflammatory factors (IL-6, IL-1β, and TNF- α), Sirt1 activity, SOD2 and HMGB1 acetylation level were also determined after the treatments. The rats showed significantly decreased body weight and fecal water content and progressively increased serum levels of D-LAC and DAO after TBI (P < 0.05) with obvious jejunal injury, significantly decreased expression levels of ZO-1 and claudin-5, lowered SOD2 and Sirt1 activity (P < 0.05), increased expression levels of LPO, ROS, and pro-inflammatory cytokines, and enhanced SOD2 and HMGB1 acetylation levels (P < 0.05). Compared with TBI+NS group, the rats in TBI+PD group showed obvious body weight regain, increased fecal water content, reduced jejunal pathologies, decreased D-LAC and DAO levels (P < 0.05), increased ZO-1, claudin-5, SOD2 expression levels and Sirt1 activity, and significantly decreased ROS, LPO, pro-inflammatory cytokines, and acetylation levels of SOD2 and HMGB1 (P < 0.05). PD alleviates oxidative stress and inflammatory response by activating Sirt1-mediated deacetylation of SOD2 and HMGB1 to improve intestinal mucosal injury in TBI rats.

Neuroprotective effects of crude extract of Crataegus songarica on a rat model of traumatic brain injury

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the protective effect of Crataegus songarica extract (CSCE) against traumatic brain injury (TBI) in rats, and the underlying mechanism of action.&#x0D; Methods: A rat model of TBI was established via tracheal intubation procedure, and the rats were treated with graded doses of CSCE. Neuronal survival was determined by Nissl staining, while neuronal apoptosis was measured using TUNEL-staining. Neurological impairments were determined based on neurological severity score (NSS).&#x0D; Results: Treatment of TBI rats with CSCE enhanced neuronal survival and decreased TUNEL-positive cell fraction in the brain cortex. The treatment prevented elevation of NSS and suppressed mRNA and protein expression levels of IL-6 and TNF-α in brain cortex. Moreover, CSCE treatment prevented TBI-mediated suppression of activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and attenuated hydrogen peroxide (H2O2) levels in TBI rat brain cortex. Treatment of TBI rats with CSCE down-regulated NF-κB expression, increased Nrf2 expression and up-regulated mRNA expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1 (NQO-1).&#x0D; Conclusion: These results suggest that CSCE prevents TBI-mediated reduction in neuronal survival and inhibits brain cortical neuronal death in rats. It improves NSS and inhibits inflammatory response via activation of Nrf2 pathway and targeting of NF-κB expression. Therefore, CSCE is a potential therapeutic agent for TBI.&#x0D; &#x0D; &#x0D; &#x0D;

Poly(butyl cyanoacrylate) nanoparticles-delivered β-nerve growth factor promotes the neurite outgrowth and reduces the mortality in the rat after traumatic brain injury

Several transport vectors, including nanoparticles, have been reported to be used for the delivery of therapeutic medicines crossing the impermeable blood-brain barrier (BBB) to treat the diseases in the central nerve system (CNS), such as traumatic brain injury (TBI). Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles, made from biocompatible material, are regarded as a better potential delivery tool than others such as gold nanoparticles due to their degradability in vivo. However, little is known whether PBCA nanoparticles can be used to deliver neurotrophic factors into the brain to treat TBI. In this study, we first synthesized PBCA-carried β-nerve growth factor, a neurotrophic agent with a large molecular weight, and then intravenously injected the compound into TBI rats. We found that despite undergoing several synthesis steps and host circulation, β-NGF was able to be successfully delivered into the injured brain by PBCA nanoparticles, still maintain its neurotrophic activity for neurite outgrowth, and reduce the mortality of TBI rats. Our findings indicate that PBCA nanoparticles, with Tween 80, are an efficient delivery vector and a protective reservoir for large molecular therapeutic agents to treat TBI intravenously.

A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats.

Brain lesions can cause neural stem cells to activate, proliferate, differentiate, and migrate to the injured area. However, after traumatic brain injury, brain tissue defects and microenvironment changes greatly affect the survival and growth of neural stem cells; the resulting reduction in the number of neural stem cells impedes effective repair of the injured area. Melatonin can promote the survival, proliferation, and differentiation of neural stem cells under adverse conditions such as oxidative stress or hypoxia that can occur after traumatic brain injury. Therefore, we investigated the therapeutic effects of melatonin combined with neural stem cells on traumatic brain injury in rats. First, in vitro studies confirmed that melatonin promoted the survival of neural stem cells deprived of oxygen and glucose. Then, we established a three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells and then used it to treat traumatic brain injury in rats. We found that treatment with the Matrigel system containing melatonin and neural stem cells decreased brain lesion volume, increased the number of surviving neurons, and improved recovery of neurological function compared with treatment with Matrigel alone, neural stem cells alone, Matrigel and neural stem cells combined, and Matrigel and melatonin combined. Our findings suggest that the three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells is a potential treatment for traumatic brain injury.

Monosialotetrahexosylganglioside Sodium Promotes the Cortical Neurogenesis in Traumatic Brain Injury Rats

To explore the effect of monosialotetrahexosylganglioside sodium on cortical neurogenesis in traumatic brain injury rats. Thirty Sprague–Dawley rats were randomly divided into the control group, the saline group and the monosialotetrahexosylganglioside sodium group. The rats traumatic brain injury model of saline group and the monosialotetrahexosylganglioside sodium group, control group rats was prepared with hydraulic controllable injury device and control group received sham operation. The levels of oxidative stress, nerve damage, cortical new born neurons, learning and memory capabilities of rats were assessed with serum malondialdehyde and superoxide dismutase levels, serum neurofilament light level and terminal deoxynucleotidyl transferase dUTP nick end labeling, neuronal nuclear protein/ bromodeoxyuridine cells and Morris water maze respectively. Compared with the control group, the level of oxidative stress was significantly increased, the nerve damage was obvious, the number of new born neurons increased, and the ability of learning and memory decreased in the other two groups. Compared with the normal saline group, the oxidative stress level was lower, the nerve damage was reduced, the number of new born neurons increases more obviously and the decline in learning and memory ability was reduced in the monosialotetrahexosylganglioside sodium group. Monosialotetrahexosylganglioside sodium can reduce the oxidative stress level, protect the nerve cells from damage and promote the neurogenesis in the cortex and promote the improvement of cognitive functions such as learning and memory in traumatic brain injury rats.

Methane-rich saline restores brain SOD activity and alleviates cognitive impairment in rats with traumatic brain injury

Clinically, methane is an anti-inflammatory gas used to treat organ damage. There is no extensive research on methane's repair of traumatic brain injury (TBI), so this study aims to investigate the role of methane and its potential mechanism. A rat TBI model was established by mechanical impact. SD rats were divided into four groups, including sham group, TBI group, 2 or 20 mL/kg methane-rich saline (MS) group. Morris water maze test revealed that MS improved cognitive function in TBI rats. HE and Nissl staining showed that MS reduced the blurring of brain tissues boundary, the number of necrotic plaques and neurons in TBI rats. In addition, ELISA revealed that MS restored the oxidative stress of TBI rats and reversed the inflammatory effect of TBI on brain cells, and TUNEL staining detected that MS inhibited cell apoptosis. Western blotting showed that MS downregulated Caspase-3 and Bax protein levels and upregulated Bcl-2 level. And MS inhibited phosphorylated expressions of Janus kinase 1 (JAK1), signal transducer and activator of the transcription (STAT1) and NF-κb-p65. In conclusion, MS improved cognitive function, reduced inflammatory response and oxidative stress and inhibited cell apoptosis to relieve rat TBI by blocking the activation of the JAK1/STAT1/NF-κb-p65 pathway.