Current neurovascular research最新文献

Background: Chemotherapy-induced peripheral neuropathy is a debilitating pain syndrome produced as a side effect of antineoplastic drugs like paclitaxel. Despite efforts, the currently available therapeutics suffer from serious drawbacks like unwanted side effects and poor efficacy and provide only symptomatic relief. Hence, there is a need to find new therapeutic alternatives for the treatment of chemotherapy-induced peripheral neuropathy.

Objective: The objective of this study was to explore the protective potential of caffeic acid phenethyl ester in paclitaxel-induced neuropathic pain.

Methods: We examined the effects of caffeic acid phenethyl ester by administering paclitaxel (2 mg/kg, intraperitoneal) to female Sprague Dawley rats on four alternate days to induce neuropathic pain, followed by the administration of caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneally).

Results: Rats that were administered paclitaxel showed a substantially diminished pain threshold and nerve functions after 28 days. A significantly increased protein expression of Wnt signalling protein (β-catenin), inflammatory marker (matrix metalloproteinase 2) and a decrease in endogenous antioxidant (nuclear factor erythroid 2-related factor 2) levels were found in paclitaxel administered rats in comparison to the naïve control group. Caffeic acid phenethyl ester (10 and 30 mg/kg, intraperitoneal) showed improvements in behavioural and nerve function parameters along with reduced expression of β-catenin, matrix metalloproteinase 2 and an increase in nuclear factor erythroid 2- related factor 2 protein expression.

Conclusion: The present study suggests that caffeic acid phenethyl ester attenuates chemotherapyinduced peripheral neuropathy via inhibition of β-catenin and matrix metalloproteinase 2 and increases nuclear factor erythroid 2-related factor 2 activation.

Objective: This study's purpose is to investigate the neuroprotective role of ethyl pyruvate (EP) in the pathogenesis of diabetic intracerebral hemorrhage.

Methods: The present study used a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and streptozotocin-induced diabetes. The C57BL/6 mice were randomly divided into 3 groups: sham operation, diabetic cerebral hemorrhage, and diabetic cerebral hemorrhage with EP. The EP (80 mg/kg) and EP (50 mg/kg) were injected intraperitoneally one day and one hour before modeling. The protein expression levels of high mobility group box 1 (HMGB1) and NOD-like receptors 3 (NLRP3) were detected with western blot. The mRNA levels of HMGB1 and toll-like receptor 4 (TLR4) were measured by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and ELISA were performed to confirm some inflammatory factors.

Results: Compared to the normal diabetic intracerebral hemorrhage group, the mRNA and protein expression levels of HMGB1 and TLR4 were downregulated in the EP-affected group with diabetic cerebral hemorrhage, together with the downregulation of the expression of inflammasomes, including NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase 1.

Conclusion: EP can reduce the inflammatory response after diabetic intracerebral hemorrhage and may inhibit the activation of inflammasomes by the HMGB1/TLR4 pathway.

Background: A certain number of patients with single subcortical small infarction (SSSI) in the lenticulostriate artery (LSA) territory present with early neurological deterioration (END).

Objective: We sought to identify a more specific predicting imaging marker for END in lenticulostriate SSSI patients.

Methods: We screened patients in a prospective hospital-based registry of stroke in the first Affiliated Hospital of Zhengzhou University from January 2015 to December 2020. Lesion locations were defined as posterior type when more than half of the lesion was located in the posterior part of the corona radiata divided by the midline, which was drawn between the tangents of the anterior and posterior horns of the lateral ventricle and was adjacent to the lateral ventricle at the same time. END was defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale score or ≥1 point. A multivariate logistic analysis was used to assess the imaging predictors for END.

Results: 418 patients were enrolled in the final data analysis. Among them, 206 (49. 3%) cases were rated as the posterior type and71 (17.0%) cases had to END. A multivariate logistic analysis showed that only the posterior type (adjusted odds ratio, 2. 126; 95% confidence interval, 1. 250-3. 614; P = 0. 005) was independently associated with the risk of END.

Conclusion: The posterior type of lesion location represented an imaging marker predicting END in lenticulostriate SSSI patients.

Objective: This study aimed to explore and analyze the effect of acupuncture on improving the enteral nutrition level and gastrointestinal dynamics in patients who had suffered a severe stroke.

Methods: A total of 122 patients who experienced a severe stroke who were treated in the intensive care unit of the Affiliated Hospital of Hebei University (China) between September 2021 and March 2022 were randomly divided into two groups as follows: 1) the observation group, the participants of which received acupuncture combined with early enteral nutrition (61 cases); 2) the control group, the participants of which received early enteral nutrition (61 cases). Following treatment, the hemoglobin, neutrophil count, blood glucose, albumin, pre-albumin, immediate postprandial antral area, antral contraction frequency (at 2 min), and antral motility index on days 1 and 7 of treatment were compared between the two groups.

Results: The total clinical effective rate was 96.72% in the observation group and 77.05% in the control group. The curative effect comparison between the two groups after seven days of treatment showed a lower probability of gastrointestinal bleeding, faster recovery of gastrointestinal motility, and a higher level of nutrient absorption in the observation group. Serum albumin, pre-albumin, hemoglobin, total lymphocyte count, immediate postprandial maximum (max) and minimum (mix) area of the gastric antrum, antral contraction frequency (at 2 min), and antral motility index were higher in the observation group than in the control group (P < 0.05). The difference in blood glucose levels between the two groups was not statistically significant (P > 0.05).

Conclusion: Acupuncture improved the enteral nutrition status of patients who had suffered a severe stroke and promoted gastrointestinal motility. The combination of acupuncture and early enteral nutrition could reduce damage to the gastrointestinal mucosal barrier caused by stress, changes in metabolism, and improved gastrointestinal function.

Background: Secretoneurin is a neuropeptide expressed from endocrine, neuroendocrine, and neural tissues. Our study aimed to investigate whether there was a relationship between secretoneurin levels and the severity of traumatic brain injury (TBI).

Methods: Ninety patients aged over 18 years who were admitted to the emergency department with head trauma between April 2020 and October 2020 and 20 healthy volunteers (control group) were included in the study. Patients were divided into three groups according to Glasgow Coma Scale scores: Mild TBI (n=33), moderate TBI (n=28), and severe TBI (n=29). The final status of the patients was evaluated in three groups: exitus, discharge with Glasgow Outcome Scale (GOS) ≤ 3 and discharge with GOS >3.

Results: The median secretoneurin levels of patients with severe TBI 31.71 (14.21-70.95) were found to be significantly higher than in those with moderate TBI [17.30 (10.71-69.27) (P=0.025), and patients with moderate TBI had a substantially higher level of secretoneurin than those with mild TBI 11.70 (6-16.25) (P<0.001). There was no statistically significant difference between the median secretoneurin levels in patients with mild TBI and the control group 10.73 (5.33-13.18) (P=0.999). The secretoneurin cut-off value of >18.13 ng/mL had a sensitivity of 83.87% and a specificity of 77.97% for poor neurologic outcomes (AUC 0.86, 95% CI: 0.77- 0.92). The secretoneurin cut-off value of >20.67 ng/mL had a sensitivity of 90.91% and a specificity of 74.68% for mortality (AUC 0.85, 95% CI: 0.76-0.92).

Conclusion: Secretoneurin can be a useful biomarker in diagnosing patients with moderate-tosevere TBI. It may also guide physicians in predicting the clinical outcome of patients with TBI.

Background: Depressive symptoms are one of the main clinical features of the cerebral small-vessel disease (CSVD). However, the pathogenesis of depressive symptoms of CSVD has not been fully studied, and a lack of effective diagnostic methodseffective diagnostic methods exists. Recently, the emerging body of evidence regarding exosomes has rendered them potentially key players in the neuropsychiatric disease theragnostic. This study's aim was to investigate serumexosome proteomic expression in CSVD patients with depressive symptoms and to screen and analyze potential biomarkers for clinical diagnosis.

Methods: Serum samples were collected from 36 CSVD patients, including 18 cerebral small-vessel disease (CSVD+D) patients with depressive clinical manifestations and 18 cerebral small-vessel disease patients that did not present depression-related clinical manifestations (CSVD-D). This investigation employed tandem mass tag (TMT) combined with mass spectrometry for sample detection and quantitative analysis of proteins. The differential proteins with significant dysregulated expression levels in patient plasma exosomes were screened and analyzed through bioinformatics techniques.

Results: This investigation focused on a global collection of 659 quantifiable proteins. Compared to the CSVD-D group, 7 up-regulated and 30 down-regulated proteins were identified in the CSVD+D group (P < 0.05). Gene ontology (GO) enrichment analyses revealed proteomic expression profile dysregulations within serum exosomes in patients with depression, such as desmosomes and keratins, rendering them as potential biomarkers. Kyoto encyclopedia of genes and genomes (KEGG) database investigations revealed the differentially expressed proteins to be highly aggregated within the estrogen signaling pathway.

Conclusion: This investigation pioneered TMT proteomic evaluation of serum exosomes within CSVD patients suffering from depression and reveals the shifts in proteomic expression profiles by serum exosomes within such patients. This study identified several important molecular / signal pathway abnormalities related to depression. These results provide a possible means to further clarify the pathogenesis of depressive symptoms of cerebrovascular disease and its diagnosis and treatment in the future.

Background: Detection or monitoring of brain damage is a clinically crucial issue. Nucleic acids in the whole blood can be used as biomarkers for brain injury. Polymerase chain reaction (PCR) which is one of the most commonly used molecular diagnostic assays requires isolated nucleic acids to initiate amplification. Currently used nucleic acid isolation procedures are complicated and require laboratory equipments.

Objective: In this study, we tried to develop a simple and convenient method to isolate nucleic acids from the whole blood sample using a tiny battery-powered electric device. The quality of the isolated nucleic acids should be suitable for PCR assay without extra preparation.

Methods: A plastic device with separation chamber was designed and printed with a 3D printer. Two platinum electrodes were placed on both sides and a battery was used to supply the electricity. To choose the optimal nucleic acid isolation condition, diverse lysis buffers and separation buffers were evaluated, and the duration and voltage of the electricity were tested. Western blot analysis and PCR assay were used to determine the quality of the separated nucleic acids.

Results: 2ul of whole blood was applied to the cathode side of the separation chamber containing 78 ul of normal saline. When the electricity at 5 V was applied for 5 min, nucleic acids were separated from segment 1 to 3 of the separation chamber. The concentration of nucleic acids peaked around 7~8 mm from cathode side. PCR assay using the separation buffer as the template was performed successfully both in conventional and realtime PCR methods. The hemoglobin in the whole blood did not show the inhibitory effect in our separation system and it may be due to structural modification of hemoglobin during electric separation.

Conclusion: Our simple electric device can separate nucleic acids from the whole blood sample by applying electricity at 5 V for 5 min. The separation buffer solution taken from the device can be used for PCR assay successfully.

Background: Spinal cord injury (SCI) is regarded as an acute neurological disorder, and astrocytes play a role in the progression of SCI.

Objective: Herein, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2)- modified rat spinal astrocytes in neurofunctional recovery after SCI.

Methods: Rat spinal astrocytes were cultured, isolated, and then identified through microscopic observation and immunofluorescence staining. Astrocytes were infected with the adenovirus vector overexpressing HIPK2 for modification, and proliferation and apoptosis of astrocytes were examined using Cell Counting Kit-8 method and flow cytometry. SCI rat models were established and treated with astrocytes or HIPK2-modified astrocytes. Subsequently, rat motor ability was analyzed via the Basso-Beattie-Bresnahan (BBB) scoring and inclined-plane test, and the damage to spinal cord tissues and neuronal survival were observed via Hematoxylin-eosin staining and Nissl staining. The levels of HIPK2, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nuclear factor erythroid 2- related transcription factor 2 (Nrf2)/antioxidant response element (ARE) pathway-related proteins were detected.

Results: Rat spinal astrocytes were harvested successfully. HIPK2 overexpression accelerated the proliferation and repressed the apoptosis of rat spinal astrocytes. Rat spinal astrocytes treatment increased BBB points and the maximum angle at which SCI rats remained stable, ameliorated damage to spinal cord tissues, increased the number of neurons, and attenuated neural damage and inflammation, while the treatment of HIPK2-modified rat spinal astrocytes imparted more pronounced effects to the neurofunctional recovery of SCI rats. Meanwhile, HIPK2-modified rat spinal astrocytes further activated the Nrf2/ARE pathway.

Conclusion: HIPK2-modified rat spinal astrocytes facilitated neurofunctional recovery and activated the Nrf2/ARE pathway after SCI.