Brain Tissue Water Content Research Articles

Study on the Neuroprotective Mechanism of Salidroside Modified with Polydopamine Nanoparticles in Regulating Notch Pathway by Inhibiting Mir-155 in Stroke Rats

Background and Purpose Stroke threatens neurological function. Salidroside is widely used to treat neurological diseases such as stroke. Previous studies have shown that miR-155 plays an important regulatory role in the pathogenesis of stroke and that the Notch pathway plays an important role in nervous system development and regeneration. Methods PDA NPs-SAL complex was prepared, a stroke rat model was constructed, and the cerebral infarction area of rats was measured. Analyze the changes of PDA NPs-SAL on rat brain tissue and evaluate the neuroprotective effect. Detect the changes in miR-155 and Notch pathway-related proteins in stroke rat models to further understand the role of miR-155 and Notch pathway in the pathogenesis of stroke and their relationship. Results Salidroside had certain protective effects on the nerves of stroke rats, and the effect of PDA NPs-SAL was more prominent. At the same time, PDA NPs-SAL promotes the Notch pathway by inhibiting miR-155, thereby exerting a neuroprotective effect on stroke rats. Conclusion Under the intervention of PDA NPs-SAL, the neurological function scores of rats were reduced, and the effect of PDA NPs-SAL was more significant. In addition, PDA NPs-SAL inhibited miR-155 and activated the Notch pathway, thereby reducing the water content of rat brain tissue and cerebral infarction area, thereby exerting a neuroprotective effect on stroke rats.

Real-time detection of cerebral edema in mice based on low-field nuclear magnetic resonance

Cerebral edema is a secondary symptom of several conditions, including stroke, liver, failure, and severe craniocerebral injury. This study aimed to propose a Low-Field Nuclear Magnetic Resonance (LF-NMR) method for rapid and nondestructive measurement of brain water content and water phase state evaluating animal brain edema models. The water transverse relaxation time (T2) distribution in brain tissues was ascertained by measuring the T2 spectrograms of mouse brain tissues following various drying durations, in accordance with the shifting law of T2 peaks. A methodological study was carried out for the determination of water content in mouse brain tissue by the LF-NMR Peak Area (LF-NMR-PA) method using CuSO4 solution as standard solution. This method was studied in comparison with the wet/dry weight method and the Partial Least Squares Regression (PLSR) prediction method in normal and MCAO model mice, and further applied to the study of mannitol treatment of cerebral edema to validate the precision and accuracy of the hydration measurements as well as the method’s impact on subsequent experiments of cerebral infarct area measurement. In the T2 spectra of mouse brain tissues, the separate peaks T21 (0–10 ms), T22 (10–100 ms), and T23 (100–1000 ms) correspond to fat and bound water, water, and free water in brain tissue, respectively. The LF-NMR-PA method had good specificity, linearity, precision, stability, reproducibility, and recovery. The accuracy and range of use of the LF-NMR-PA method were better than those of the PLSR method, and its results were not significantly different from those of the wet/dry weight method. However, the short measurement time of the LF-NMR-PA method ensured the integrity of the tissues, and the determination of the moisture by this method did not have a significant effect on the subsequent determination of the area of cerebral infarction, which ensured the consistency of the experimental results.

Effects of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke.

To explore the impacts of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke, seventy-two male C57BL/6 mice were randomly separated into 6 groups (n=12), the experimental group (EG, day 1, day 3 and day 7) and the control group (CG, day 1, day 3 and day 7). The mouse cerebral hemorrhage model was established by collagenase injection, and the EG received 0.4 mL fecal filtrate of healthy mice once a day, and the CG received the same amount of normal saline transplantation. The mNSS score, hematoma volume and cerebral edema content were used to evaluate nerve function injury and brain injury degree at each time point after operation. The expressions of inflammatory factors were detected by western blot. We found that at each time point after operation, compared with the CG, nerve function deficit scores of mice in the EG declined (P<0.05), the water content of mice brain tissue in the EG declined (P<0.05), and the protein expressions of inflammatory factors in the EG were decreased (P<0.05). Relative to the CG, the volume of hematoma in the EG declined on day 3 along with day 7 after operation (P<0.05). In conclusion, intestinal flora can reduce cerebral hemorrhage area and brain tissue inflammation, and then improve the performance of nerve function deficit in acute hemorrhagic stroke.

Curcumin Alleviates Microglia-Mediated Neuroinflammation and Neuronal Ferroptosis Following Experimental Subarachnoid Hemorrhage by Modulating the Nrf2/HO-1 Signaling Pathway.

Early brain injury caused by subarachnoid hemorrhage (SAH) is associated with inflammatory response and ferroptosis. Curcumin alleviates neuroinflammation and oxidative stress by as yet unknown neuroprotective mechanisms. The objective of this study was to investigate the impact of curcumin on neuronal ferroptosis and microglia-induced neuroinflammation following SAH. By examining Nrf2/HO-1 expression levels and ferroptosis biomarkers expression both in vitro and in vivo, it was demonstrated that curcumin effectively suppressed ferroptosis in neurons after SAH through modulation of the Nrf2/HO-1 signaling pathway. Furthermore, by analyzing the expression levels of Nrf2, HO-1, p-p65, and inflammation-related genes, it was confirmed that curcumin could prevent the upregulation of pro-inflammatory factors following SAH by regulating the Nrf2/HO-1/NF-κB signaling pathway in microglia. The ability of curcumin to reduce neuronal damage and cerebral edemas after SAH in mice was validated using TUNEL staining, Nissl staining, and measurement of brain tissue water content. Additionally, through implementation of the modified Garcia test, open field test, and Y-maze test, it was established that curcumin ameliorated neurobehavioral impairments in mice post-SAH. Taken together, these data suggest that curcumin may offer a promising therapeutic approach for improving outcomes following SAH by concurrently attenuating neuronal ferroptosis and reducing neuroinflammation.

Mesenchymal stem cell-derived exosomes overexpressing SRC-3 protect mice from cerebral ischemia by inhibiting ferroptosis

BackgroundThe treatment for cerebral ischemia remains limited, and new therapeutic strategies are urgently needed. Exosome has shown great promise for the treatment of cerebral ischemia. Steroid receptor coactivator-3 (SRC-3) was reported to be involved in neurological performances. In this study, we aimed to investigate the protective effects of mesenchymal stem cell (MSC)-derived exosomes overexpressing SRC-3 on cerebral ischemia in mice. MethodsThe mice were treated with an intracerebroventricular injection of GFP-overexpressed exosomes (GFP-exo) and SRC-3-overexpressed exosomes (SRC3-exo) in a middle cerebral artery occlusion (MCAO) model of cerebral ischemia. ResultsThe results showed that SRC3-exo treatment significantly inhibited lipid peroxidation and ferroptosis of the neurons subjected to oxygen-glucose deprivation. It further suppressed the activation of microglia and astrocytes, and decreased the production of pro-inflammatory cytokines in the brains of MCAO mice. Furthermore, SRC3-exo treatment reduced the water content of brain tissue and infarct size, which alleviated the neurological damage and improved neurological performances in the MCAO mice. ConclusionsOur results suggest that MSC-derived exosomes expressing SRC3 can be a therapeutic strategy for cerebral ischemia by inhibiting ferroptosis.

Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury by regulating the Cx43

PurposeTo explore the mechanism by which Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury (TBI). MethodsThe oxygen -glucose deprivation/recovery (OGD/R) cell model was constructed to simulate the pathological state of astrocytes in a TBI environment. The viability of astrocytes was measured by CCK-8, and the cytoskeleton changes were observed by Phalloidin- TRITC staining. The expressions of differentiation markers, Cx43 and phosphorylated Cx43 (P-Cx43) of A1/A2 astrocytes were detected by Western blot, and the complement C3 and S100A10 of A1/A2 astrocytes were detected by ELISA. The TBI rat model was established. The water content of brain tissue was measured by dry-wet specific gravity method, the pathological morphology of brain tissue in cortical injury area was observed by HE staining method, ROS was detected by fluorescence quantitative method, Cx43 expression was detected by immunohistochemistry method, and the differentiation markers of A1/A2 astrocytes were detected by immunofluorescence. ResultsIn the TBI environment, astrocytes showed decreased cell viability, blurred skeleton, and increased expression of Cx43. In TBI rats, the water content of brain tissue increased, the brain tissue in the cortex injury area was seriously damaged, ROS and Cx43 expression were significantly increased, and mainly distributed in A2 astrocytes. Remazolam can reverse the above results after the intervention. ConclusionRemazolam affects the phenotype and function of astrocytes to improve TBI via regulating Cx43, and plays a role in protecting the neurological function of TBI rats.

Activation of GPER-1 Attenuates Traumatic Brain Injury-Induced Neurological Impairments in Mice.

This study aimed to investigate the effects of G1-activated G protein-coupled estrogen receptor 1 (GPER1) on neurological impairments and neuroinflammation in traumatic brain injury (TBI) mice. The controlled cortical impingement (CCI) method was used to establish the TBI model. The mice were subjected to ovariectomy (OVX) for two weeks prior to modeling. GPER1 agonist G1 was administered by intracerebroventricular injection. Brain tissue water content was detected by wet/dry method, and blood-brain barrier damage was detected by Evans blue extravasation. The neurological impairments in mice were evaluated by open field test, Y-maze test, nest-building test, object location memory test and novel object recognition test. Ionized calcium-binding adapter molecule 1 (Iba1) staining was used to indicate the activation of microglia. Expression of M1/M2-type microglia markers and inflammatory factors were evaluated by ELISA and qRT-PCR. The G1 administration significantly reduced cerebral edema and Evans blue extravasation at injury ipsilateral cortex and basal ganglia in TBI mice. Activation of GPER1 by G1 improved the anxiety behavior and the cognitive dysfunction of mice induced by TBI. G1 administration significantly decreased Iba1-positive staining cells and the mRNA levels of CD86, macrophage cationic peptide 1 (Mcp-1), nitric oxide synthase 2 (Nos2), interleukin 1 beta (IL-1β), and macrophage inflammatory protein-2 (MIP-2), while increased the mRNA levels of interleukin 10 (IL-10), arginase1 (Arg-1) and CD206. Activation of GPER1 through G1 administration has the potential to ameliorate cognitive dysfunction induced by TBI in mice. It may also inhibit the activation of M1 microglia in cortical tissue resulting from TBI, while promoting the activation of M2 microglia and contributing to the regulation of inflammatory responses.

Polygalasaponin F ameliorates middle cerebral artery occlusion-induced focal ischemia / reperfusion injury in rats through inhibiting TXNIP/NLRP3 signaling pathway

BackgroundPolygalasaponin F (PGSF), an oleanane triterpenoid saponin extracted from Polygala japonica, has been demonstrated with neuroprotective effect. However, the therapeutic effects and mechanisms of PGSF on focal ischemia remain unknown; MethodsIn this study, male Sprague Dawley (SD) rats aged 6–8 weeks were initially selected to establish a rat model of middle cerebral artery occlusion (MCAO) to evaluate the therapeutic effect of PGSF intervention and to investigate the impact of PGSF on the thioredoxin-interacting protein/NOD-, LRR-, and pyrin domain-containing protein 3 (TXNIP/NLRP3) inflammatory pathway. Secondly, brain neuron cells were isolated, and the cells received oxygen-glucose deprivation/reoxygenation (OGD/R) culture to establish the cell injury model in vitro. The mechanism of PGSF on the TXNIP/NLRP3 pathway was further validated; ResultsOur results showed that PGSF treatment reduced neurological scores, brain tissue water content and infarct volume and ameliorated the pathological changes in cerebral cortex in MCAO-induced focal ischemia rats. The TNF-α, IL-1β and IL-6 levels decreased in MCAO-induced focal ischemia rats after PGSF treatment. Moreover, PGSF down-regulated the protein expressions of TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 in MCAO-induced focal ischemia rats. Meanwhile, PGSF treatment inhibited apoptosis, and reduced the levels of ROS, inflammatory cytokine and TXNIP/NLRP3 pathway-related proteins (TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18) in OGD/R-induced neuronal injury cells. Finally, PGSF treatment also disrupted the interaction between NLRP3 and TXNIP in vitro; ConclusionsOur study demonstrated the therapeutic effects of PGSF on MCAO-induced focal ischemia rats. Moreover, the neuroprotective mechanism of PGSF on focal ischemia was associated with the inhibition of TXNIP/NLRP3 signaling pathway.

Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway.

Oxidative stress (OS) and inflammatory reactions play pivotal roles in secondary brain injury after traumatic brain injury (TBI). Histone deacetylase 3 (HDAC3) controls the acetylation of histones and non-histones, which has a significant impact on the central nervous system's reaction to damage. This research determined the implications of RGFP966, a new and specific inhibitor of HDAC3, for the antioxidant (AO) systems mediated by nuclear factor erythroid2-related factor 2 (Nrf2) and the Nod-like receptor protein 3 (NLRP3) inflammasome in TBI. The study also studied the underlying mechanisms of RGFP966's actions. Our objective was to examine the impacts and underlying RGFP966 mechanisms in TBI. In vitro, a rat cortical neuron OS model was induced by H2O2, followed by the addition of RGFP966 to the culture medium. Neurons were collected after 24h for western blot (WB), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 2'-7'-dichlorodihydrofluorescein diacetate staining. In vivo, RGFP966 (10mg/kg) was administered post-TBI. Brain tissue water content and modified neurological severity scores were assessed 72h post-injury. Cortical tissues surrounding the focal injury were subjected to western blot, TUNEL staining, Nissl staining and immunofluorescence/immunohistochemistry staining, and malondialdehyde level, hindered glutathione content and superoxide dismutase activity were measured. Serum was collected for the enzyme-linked immunosorbent assay. Nrf2-specific shRNA lentivirus was injected into the lateral ventricle of rats for 7days, and cerebral cortex tissue was analyzed by WB and real-time polymerase chain reaction. During in vitro and in vivo experiments, RGFP966 suppressed HDAC3 expression, promoted Nrf2 nuclear translocation, activated downstream AO enzymes, mitigated excessive reactive oxygen species production and alleviated nerve cell apoptosis. RGFP966 effectively reduced brain edema and histological damage and enhanced neurological and cognitive function in rats with TBI. RGFP966 markedly inhibited NLRP3 inflammasome activation mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4). Nrf2 knockdown in TBI rats attenuated the AO and anti-inflammatory, neuroprotective impacts of RGFP966. Overall, our findings demonstrate that RGFP966 can mitigate the first brain damage and neurological impairments in TBI. The underlying mechanism involves triggering the Nrf2-mediated AO system and negatively regulating the HMGB1/TLR4-mediated NLRP3 inflammasome pathway.

Rosiglitazone inhibits acyl-CoA synthetase long-chain family number 4 and improves secondary brain injury in a rat model of surgical brain injury.

Ferroptosis is a recently discovered non-apoptotic form of cellular death. Acyl-CoA synthetase long-chain family number 4 (ACSL4) is necessary for iron-dependent cellular death, and reactive oxygen species (ROS) produced by ACSL4 are the executioners of ferroptosis. Rosiglitazone improves ferroptosis by inhibiting ACSL4. There is no research indicating whether ACSL4 plays a role in cell death after surgical brain injury (SBI). This study aimed to investigate the role of ACSL4 in SBI via the ferroptosis pathway. Ninety male Sprague-Dawley rats were examined using a model of SBI. Subsequently, the inhibitory effect of rosiglitazone on ACSL4 was assessed via western blot, real-time polymerase chain reaction (PCR), immunofluorescence, fluoro-jade C staining, Perl's staining, ROS assay, and neurological scoring. The results showed that compared with the Sham group, the protein levels of ACSL4 and transferrin were significantly increased after SBI. Administration of rosiglitazone significantly reduced neuronal necrosis, iron deposition, brain water content and ROS in brain tissue and ameliorated neurological deficits at 48 h after SBI, which was concomitant with decreased transferrin expression. These findings demonstrate that SBI-induced upregulation of ACSL4 may be partly mediated by the ferroptosis pathway, which can be reversed by rosiglitazone administration.

Expression and Related Mechanism of miR-744 in Ischemia-reperfusion Rat Model.

To study the expression of miR-744 in the rat model of ischemia-reperfusion (I-R) and its related mechanism. Seventy-five Wistar rats were randomly divided into 3 groups: sham operation group (SOG), model group (MG) and miR-744 group, with 25 in each group. The expression levels of IL-1β, IL-6 and TNF-α were observed by Western Blot after the model preparation, while miR-744 expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The cerebral infarction volume of rats in the MG was significantly larger than that in the miR-744 group (P<0.05). The MG exhibited a markedly higher brain tissue water content than the SOG and the miR-744 group (P<0.05). When compared within the latter two groups, the brain tissue water content in the SOG was significantly lower than that in the miR-744 group (P<0.05). As to miR-744 expression, the relative expression of miR-744 in the brain tissue of the MG was the lowest among the three groups. When compared within the remaining two groups, the miR-744 expression of the miR-744 group was remarkably higher than that of the SOG (P<0.05). In terms of the expression levels of inflammatory factors, the expressions of IL-1β, IL-6 and TNF-α in the brain tissue of the SOG and the miR-744 group were significantly lower than those in the MG, and those of the SOG were significantly lower than that of the miR-744 group. MiR-744 may be involved in the development and progression of I-R in rats, and its mechanism may be related to the regulation of inflammatory response.

Effects of hydrogen gas on NOD-like receptor protein 3 inflammasomes in the cerebral cortex of rats with traumatic brain injury

To investigate the effect of hydrogen gas on NOD-like receptor protein 3 (NLRP3) inflammasomes in the cerebral cortex of rats with traumatic brain injury (TBI). 120 adult male Sprague-Dawley (SD) rates were randomly divided into 5 groups (n = 24): sham operation group (S group), TBI model group (T group), TBI+NLRP3 inhibitor MCC950 group (T+M group), TBI+hydrogen gas group (T+H group), TBI+hydrogen gas+MCC950 group (T+H+M group). TBI model was established by controlled cortical impact. NLRP3 inhibitor MCC950 (10 mg/kg) was intraperitoneally injected for 14 consecutive days before TBI operation in T+M and T+H+M groups. 2% hydrogen inhalation was given for 1 hour at 1 hour and 3 hours after TBI operation in T+H and T+H+M groups. At 6 hours after TBI operation, the pericontusional cortex tissues were obtained, the content of Evans blue (EB) was detected to evaluate the permeability of the blood-brain barrier. Water content in brain tissue was detected. The cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) and the neuronal apoptosis index was calculated. The expressions of Bcl-2, Bax, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 p20 were detected by Western blotting. The levels of interleukins (IL-1β, IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the S group, the content of EB in cerebral cortex, water content in brain tissue, apoptosis index and the expressions of Bax, NLRP3, ASC, caspase-1 p20 in T group were significantly increased, the expression of Bcl-2 was down-regulated, the levels of IL-1β and IL-18 were increased [the content of EB (μg/g): 87.57±6.89 vs. 10.54±1.15, water content in brain tissues: (83.79±2.74)% vs. (74.50±1.19)%, apoptotic index: (62.66±5.33)% vs. (4.61±0.96)%, Bax/β-actin: 4.20±0.44 vs. 1, NLRP3/β-actin: 3.55±0.31 vs. 1, ASC/β-actin: 3.10±0.26 vs. 1, caspase-1 p20/β-actin: 3.28±0.24 vs. 1, Bcl-2/β-actin: 0.23±0.03 vs. 1, IL-1β (ng/g): 221.58±19.15 vs. 27.15±3.27, IL-18 (ng/g): 87.26±7.17 vs. 12.10±1.85, all P < 0.05]. Compared with the T group, the T+M, T+H and T+H+M groups had significant reductions in the content of EB and water content in brain tissue, apoptotic index of the cerebral cortex, the expressions of Bax, NLRP3, and caspase-1 p20 in the brain tissue and the levels of IL-1β and IL-18, significant increases in the expression of Bcl-2. However, there was no significant difference in ASC expression. Compared with the T+H group, the content of EB in the cerebral cortex, water content in brain tissue, and apoptotic index, and the expressions of Bax, NLRP3 and caspase-1 p20 were further down-regulated in T+H+M group, the expression of Bcl-2 was further up-regulated, the levels of IL-1β and IL-18 were further decreased [the content of EB (μg/g): 40.49±3.15 vs. 51.96±4.69, water content in brain tissue: (76.58±1.04)% vs. (78.76±1.16)%, apoptotic index: (32.22±3.44)% vs. (38.54±3.89)%, Bax/β-actin: 1.92±0.16 vs. 2.56±0.21, NLRP3/β-actin: 1.94±0.14 vs. 2.37±0.24, caspase-1 p20/β-actin: 1.97±0.17 vs. 2.31±0.19, Bcl-2/β-actin: 0.82±0.07 vs. 0.52±0.04, IL-1β (ng/g): 86.23±7.09 vs. 110.44±10.48, IL-18 (ng/g): 40.18±3.22 vs. 46.23±4.02, all P < 0.05], but there were no statistical significance in all the indicators between T+M group and T+H group. The mechanism by which hydrogen gas alleviates TBI may be related to inhibiting NLRP3 inflammasomes in the cerebral cortex of rats.

Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats.

Glutamine (Gln) is an immunomodulatory protein that mediates oxidative stress, inflammation, and apoptosis, but has not been reported in the treatment of hyperoxia (Hyp)-induced brain injury. The aim of this study was to determine whether Gln could improve hyp-induced brain injury in neonatal rats to and later learning and memory dysfunction, and to explore its possible mechanisms. We prepared a model of neonatal rat brain injury caused by normobaric hyperoxia while administered with Gln for 7days for evaluation. Learning memory function was assessed with the Morris water maze test. Histological analysis, protein expression analysis, oxidative stress and inflammation level analysis were performed using hippocampal tissue. Gln treatment significantly reduced brain tissue water content, oxidative stress levels, microglia activation and inflammatory factor expression, and attenuated tissue damage and apoptosis in the hippocampal region. Gln ameliorates hyp-induced learning, memory impairment in neonatal rats in water maze test. It also increased MKP-1 protein expression and decreased p-p38, p-ERK and p-JNK. Therefore, it is hypothesized that Gln may exert neuroprotective effects by increasing MKP-1 expression to negatively regulate MAPK signaling, with potential cognitive improvement in hyp-induced brain injury.

Combination of Baicalin and Gardenoside Mitigates Brain Damage by Lowering AQP-4 Expression Levels in Rat Model of Cerebral Ischemia/Reperfusion

This study focused on the effects of the combination of baicalin (BC) and gardenoside (GD) (7:3) on blood-brain barrier (BBB) permeability, brain tissue water content, and aquaporin-4 (AQP-4) expression in rats with cerebral ischemia-reperfusion (I/R) injury. The previous research conducted by the investigators demonstrated that the combination of BC and GD (7:3) has anti-ischemic properties. Further research was conducted to determine the mechanism underlying the reduction in cerebral edema.

FERM domain containing kindlin 1 knockdown attenuates inflammation induced by intracerebral hemorrhage in rats via NLR family pyrin domain containing 3/nuclear factor kappa B pathway.

Intracerebral hemorrhage (ICH) is an incurable neurological disease. Microglia activation and its related inflammation contribute to ICH-associated brain damage. FERM domain containing kindlin 1 (FERMT1) is an integrin-binding protein that participates in microglia-associated inflammation, but its role in ICH is unclear. An ICH model was constructed by injecting 50 µl of autologous blood into the bregma of rats. FERMT1 siRNA was injected into the right ventricle of the rat for knockdown of FERMT1. A significant striatal hematoma was observed in ICH rats. FERMT1 knockdown reduced the water content of brain tissue, alleviated brain hematoma and improved behavioral function in ICH rats. FERMT1 knockdown reduced microglia activity, inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and decreased the expression of inflammatory factors including IL-1β and IL-18 in the peri-hematoma tissues. BV2 microglial cells were transfected with FERMT1 siRNA and incubated with 60 µM Hemin for 24 h. Activation of NLRP3 inflammasome induced by hemin were reduced in microglia when FERMT1 was knocked down, leading to decreased production of inflammatory factors IL-1β and IL-18. In addition, knockdown of FERMT1 prevented the activation of nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. Our findings suggested that down-regulation of FERMT1 attenuated microglial inflammation and brain damage induced by ICH via NLRP3/NF-κB pathway. FERMT1 is a key regulator of inflammatory damage in rats after ICH.

Application of dredging fu-organs in cerebral edema after stroke

Stroke is one of the most common diseases in neurology, and the brain edema after stroke is an important factor affecting the prognosis of patients. It is particularly important to reduce the volume of brain edema in clinic. By studying the mechanism of Tongfu agent, it is shown that it can effectively reduce the water content of brain tissue by inhibiting the expression of AQP-4, reducing the permeability of blood-brain barrier and reducing the damage of inflammatory molecules, and it has achieved good curative effect in clinic, which is one of the common treatment methods for brain edema.

On Net Water Uptake in Posttraumatic Ischemia Foci.

The influence of cerebral edema and resultant secondary complications on the clinical outcome of traumatic brain injury (TBI) is well known. Clinical studies of brain water homeostasis dynamics in TBI are limited, which determines the relevance of our work. The purpose is to study changes in brain water homeostasis after TBI of varying severity compared to corresponding cerebral microcirculation parameters. This non-randomized retrospective single-center study complies with the Helsinki Declaration for patient's studies. The study included 128 patients with posttraumatic ischemia (PCI) after moderate-to-severe TBI in the middle cerebral artery territory who were admitted to the hospital between July 2015 and February 2022. PCI was evaluated by perfusion computed tomography (CT), and brain edema was determined using net water uptake (NWU) on baseline CT images. The patients were allocated according to Marshall's classification. Multivariate linear regression models were performed to analyze data. NWU in PCI areas were significantly higher than in patients with its absence (8.1% vs. 4.2%, accordingly; p<0.001). In the multivariable regression analysis, the mean transit time increase was significantly and independently associated with higher NWU (R2=0.089, p<0.01). In the PCI zone, cerebral blood flow, cerebral blood volume, and time to peak were not significantly associated with NWU values (p>0.05). No significant differences were observed between the NWU values in PCI foci in different Marshall groups (p=0.308). Marshall's classification does not predict the progression of posttraumatic ischemia. The blood passage delays through the cerebral microvascular bed is associated with brain tissue water content increase in the PCI focus.

Targeted Therapy of Tuberculous Meningitis in Rats with Methylprednisolone Composite Nanoparticles.

It was to investigate the targeted therapeutic effect of methylprednisolone (MPS) composite nanoparticles (NPs) on tuberculous meningitis (TBM) in rats. A total of 180 special pathogen-free (SPF) Sprague Dawley (SD) rats (male) were randomly and equally assigned to the normal control group, TBM infection group, and TBM treatment group. Those in the TBM infection group and the TBM treatment group were injected with Mycobacterium tuberculosis suspension via the tail vein. After the TBM model was established, rats in the TBM treatment group were injected intraperitoneally with methylprednisolone-nano sterically stabilized liposomes (MPS-NSSLs), and those in the normal control group were injected with an equal amount of normal saline. MPS-NSSLs were prepared, and their quality evaluation, encapsulation rate, drug-lipid ratio, and stability were detected. The particle size distribution of MPS-NSSLs was 95.4 ± 0.7 nm, showing a complete spherical structure, and the encapsulation rate was 91.24 ± 0.27 %, and the drug-lipid ratio was about 0.4. After 7 days of treatment, the water content of brain tissue in the TBM infection group was drastically superior to that in the control group (P<0.05); Evans blue (EB) content in the TBM infection group was dramatically superior to that in the control group (P<0.05). The TBM rat model was successfully established, and this model verified that MPS-NSSLs had the characteristics of high efficiency and low toxicity in the treatment of TBM rats.

Scalp acupuncture regulates hypothalamic V1aR/CaMKⅡ/AQP4 signaling pathway in rats with focal cerebral ischemia

To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(V1aR), phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ), and aquaporin 4(AQP4) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke. A total of 96 male SD rats were randomly divided into normal， model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with V1aR inhibitor (30 μg/kg)，once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKⅡ and AQP4 proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of V1aR mRNA in hypothalamus was detected by real-time PCR. Compared with the normal group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly increased (P<0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic V1aR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP4 positive expression levels were significantly decreased (P<0.01) in the inhibitor and scalp acupuncture groups. Regulating the signaling pathway of V1aR/CaMKⅡ/AQP4 in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.

Dexmedetomidine (Dex) exerts protective effects on rat neuronal cells injured by cerebral ischemia/reperfusion via regulating the Sphk1/S1P signaling pathway

AimTo investigate the influence of dexmedetomidine (Dex) on cerebral ischemia/reperfusion (I/R)-injured rat neuronal cells by regulating the Sphk1/S1P pathway. MethodsThe rats were divided into the following groups, with 18 rats in each group categorized on the basis of random number tables: sham (Sham), I/R (I/R), Dex, Sphk1 inhibitor (PF-543), and Dex together with the Sphk1 agonist phorbol-12-myristate-13-acetate (Dex+PMA). The neurological functions of the rats were assessed by the Longa scoring system at 24 h post reperfusion. The area of brain infarction was inspected using 2,3,5-triphenyltetrazolium chloride staining, and the water content of brain tissue was determined by the dry-wet weight method. The morphology of neurons in the CA1 region of the rat hippocampus was inspected using Nissl staining, while the apoptosis of neurons in this region was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling staining. The Sphk1 and S1P protein levels were determined by immunofluorescence and western blotting, respectively. ResultsCompared to the I/R group, rats in the Dex, PF-543, and Dex+PMA groups had a significantly lower neurological function score, as well as lower brain water content and a decreased infarction area. Moreover, the apoptotic index of the neurons and the Sphk1 and S1P levels in the hippocampal CA1 region were significantly lower in these groups (p<0.05). PMA, an agonist of Sphk1, was able to reverse the protective effects of Dex on I/R-induced neuronal cell injury. ConclusionDex could protect cerebral I/R-induced neuronal cell injury by suppressing the Sphk1/S1P signaling pathway.