Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study.

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (ß = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

The effect of green channel for stroke patients on treatment of severe aneurysmal subarachnoid hemorrhage.

PURPOSE: To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage. METHODS: This is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. RESULTS: A total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p = 0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p = 0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p = 0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p = 0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p = 0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p = 0.026). CONCLUSION: The green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.

Glucose metabolism: A link between traumatic brain injury and Alzheimer's disease.

Traumatic brain injury (TBI), a growing public health problem, is a leading cause of death and disability worldwide, although its prevention measures and clinical cares are substantially improved. Increasing evidence shows that TBI may increase the risk of mood disorders and neurodegenerative diseases, including Alzheimer's disease (AD). However, the complex relationship between TBI and AD remains elusive. Metabolic dysfunction has been the common pathology in both TBI and AD. On the one hand, TBI perturbs the glucose metabolism of the brain, and causes energy crisis and subsequent hyperglycolysis. On the other hand, glucose deprivation promotes amyloidogenesis via ß-site APP cleaving enzyme-1 dependent mechanism, and triggers tau pathology and synaptic function. Recent findings suggest that TBI might facilitate Alzheimer's pathogenesis by altering metabolism, which provides clues to metabolic link between TBI and AD. In this review, we will explore how TBI-induced metabolic changes contribute to the development of AD.

Effects of progesterone vs. dexamethasone on brain oedema and inflammatory responses following experimental brain resection.

BACKGROUND: Dexamethasone (DEXA) is commonly used to reduce brain swelling during neurosurgical procedures. DEXA, however, has many side-effects that can increase the risks of post-operative complications. In contrast, progesterone (PRO) has fewer side-effects and has been found to be neuroprotective on traumatic brain injury (TBI). Whether PRO may be used as an alternative to DEXA during routine procedures has not been fully explored. OBJECT: To compare the effects of DEXA and PRO on surgical brain injury (SBI). METHODS: Seventy-five adult male Sprague Dawley rats were randomized into five groups: (1) SBI + drug vehicle (peanut oil, 1 ml kg(-1)); (2) SBI + DEXA (1 mg kg(-1)); (3) SBI + low-dose PRO (10 mg kg(-1)); (4) SBI + high-dose PRO (20 mg kg(-1)); and (5) sham SBI + drug vehicle. Magnetic resonance imaging study and assessments of brain water content (BWC), blood-brain barrier (BBB) permeability, cellular inflammatory responses and matrix metalloproteinase 9 (MMP-9) expression were conducted. RESULTS: This model consistently resulted in increased BWC and BBB disruption. PRO reduced astrocyte and microglia responses and attenuated brain oedema with preservation of BBB. A significant down-regulation of MMP-9 expression occurred in the PRO 20 group. CONCLUSIONS: PRO is as effective as DEXA in reducing brain oedema and inflammation following SBI; 10 mg kg(-1) of PRO was demonstrated to be more effective in relieving acute cellular inflammatory responses.

Quantitative computer tomography analysis of post-operative subdural fluid volume predicts recurrence of chronic subdural haematoma.

BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.

Application of minimally invasive surgery in traumatic brain injury.

This article aims to expound the essence of minimally invasive surgery as well as when and how to use it in craniocerebral trauma surgery according to the characteristics of the disease. In neurosurgery, the importance of tissue protection should be from the inside to the outside, i.e. brain--dura--skull--scalp. In this article, I want to share my opinion and our team's experience in terms of selecting surgical approaches and incision, surgical treatment of the skull, dura handling, intracranial operation and placement of drainage based on the above theory. I hope this will be helpful for trauma surgeons.

Tandem Mass Tag-based proteomics analysis reveals the vital role of inflammation in traumatic brain injury in a mouse model.

Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers. Therefore, it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury (TBI). In this study, we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI. Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses, including complement and coagulation cascades, as well as chemokine signaling pathways. Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1, RelA, IRF1, STAT1, and Spi1 play pivotal roles in the secondary injury that occurs after TBI, which further corroborates the functional enrichment for inflammatory factors. Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury.

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury (sub-acute phase), genome-wide transcriptomic data showed that interleukin 17A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17A may be a promising therapeutic target for traumatic brain injury.

[Research on the relationship between levels of soluble cluster of differentiation 40 ligand, matrix metalloproteinase 9 and pregnancy-associated plasma protein A in serum and stability of carotid plaques].

OBJECTIVES: To study the relationship between serum levels of some inflammatory markers and stability of carotid plaques in the patients with carotid plaques and evaluate the ability of each serum marker in identifying vulnerable carotid plaques. METHODS: The study included 65 consecutive patients with carotid plaques confirmed by imaging examinations from March 2008 to March 2010. All the patients were classified as stable plaques group (n = 21) and unstable plaques group (n = 44) according to the characteristic findings of the plaques in MRI such as the thickness of fibrous cap, the existence of large lipid core and the intra-plaque hemorrhage. The patients of unstable plaques group were further classified as unruptured plaques group (n = 29) and rupture plaques group (n = 15) according to the integrity of fibrous cap. Serum levels of soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase 9 (MMP-9) and pregnancy-associated plasma protein A (PAPP-A) were determined by ELISA. RESULTS: Serum levels of sCD40L and MMP-9 in patients of unstable plaques group, unruptured plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (SCD40L: χ(2) = 6.45, 12.04 and 16.23, P < 0.01; MMP-9; F = 2.55, 5.10 and 4.69, P < 0.05). Serum levels of PAPP-A in patients of unstable plaques group and rupture plaques group were all significantly enhanced compared to individuals of stable plaques group (χ(2) = 11.71 and 13.55, P < 0.05). Serum levels of PAPP-A in patients of rupture plaques group were significantly enhanced compared to individuals of unruptured plaques group (χ(2) = 13.19, P = 0.000). sCD40L ≥ 673.22 ng/L (OR = 22.47, 95%CI: 2.11 - 239.81, P = 0.010), MMP-9 ≥ 84.09 µg/L (OR = 10.01, 95%CI: 1.74 - 57.78, P = 0.010) and PAPP-A ≥ 0.101 µg/L (OR = 14.29, 95%CI: 2.69 - 75.90, P = 0.002) were all significantly correlated with the vulnerability of carotid plaques. CONCLUSIONS: There appear to be a relationship between the serum levels of sCD40L, MMP-9 and PAPP-A and the stability of carotid plaques in patients with carotid plaques. High serum levels of the above-mentioned markers may indicate that the plaques were vulnerable or ruptured.

Genome-wide interrogation of transfer RNA-derived small RNAs in a mouse model of traumatic brain injury.

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that tsRNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether tsRNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated tsRNA and messenger RNA (mRNA) transcriptome sequencing were used. The results revealed that 103 tsRNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 tsRNAs were upregulated and 47 tsRNAs were downregulated. Based on microRNA-like seed matching and Pearson correlation analysis, 57 differentially expressed tsRNA-mRNA interaction pairs were identified, including 29 tsRNAs and 26 mRNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that tsRNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee (approval No. 20190411) on April 11, 2019.

Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury.

The heterogeneity of traumatic brain injury (TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients. Targeting common processes across species may be an innovative strategy to combat debilitating TBI. In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact. The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus (ID: GSE79441) at the National Center for Biotechnology Information. For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI. Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways. These findings were further corroborated by gene set enrichment analysis. Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription (STAT), basic leucine zipper (BZIP), Rel homology domain (RHD), and interferon regulatory factor (IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation. These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI. The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee (approval No. 201802001) on June 6, 2018.

Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury.

Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability, inhibit free radicals, and reduce cerebrospinal fluid production. According to the latest guidelines for the treatment of traumatic brain injury in the United States, high-dose glucocorticoids cause neurological damage. To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect, rat controlled cortical impact models of traumatic brain injury were established. At 1 hour and 2 days after surgery, rat models were intraperitoneally administered dexamethasone 10 mg/kg. The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment. The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway. Western blot analysis and immunohistochemistry results showed that Ndufv2, Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group. These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits (Ndufs2 and Ndufv2), increase the expression of mitochondrial enzyme Maob, and upregulate synaptic-transmission-related protein Gria3. These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone. The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute (approval No. 201802001) on June 6, 2018.

Clinical Features, Intradural Transcavernous Surgical Management, and Outcomes of Giant Cavernous Sinus Hemangiomas: A Single-Institution Experience.

BACKGROUND: Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. Stereotactic radiosurgery is an effective treatment for small CSHs. The optimal treatment for giant CSHs is controversial. This study reports advantages of a complete intradural transcavernous approach in total resection of CSHs. METHODS: Between January 2012 and January 2017, 15 patients with giant CSHs were treated surgically. All cases were evaluated with a contrast-enhanced magnetic resonance imaging scan and confirmed histopathologically. A complete intradural approach was used for all patients. Clinical manifestations, radiographic characteristics, operative techniques, and outcomes of patients were analyzed. RESULTS: Headache was the most common initial symptom, followed by decreased visual acuity and diplopia. Postoperative magnetic resonance imaging showed that gross total resection was achieved in 13 patients. Two patients had experienced total ipsilateral visual loss for several years before surgery; vision improved in all remaining patients with preoperative visual diminution. The most common early neurologic deficit was cranial nerve VI dysfunction, which was observed in 9 patients (60%; 5 new deficits). Only 2 patients (13.3%) experienced permanent morbidity on long-term follow-up. The early postoperative morbidity rate for cranial nerve III dysfunction was 33.3% (5 patients), and only 1 patient (6.7%) experienced permanent morbidity. Four patients (26.7%) had slight postoperative facial numbness. CONCLUSIONS: Surgical total resection is the primary and reasonable choice for giant CSHs. Microsurgical resection of giant CSHs through a completely intradural transcavernous approach is an alternative treatment option for giant CSHs.

Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma.

BACKGROUND: Although various monitoring techniques have been used routinely in the treatment of the lesions in the skull base, iatrogenic facial paresis or paralysis remains a significant clinical problem. The aim of this study was to investigate the effect of intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation on preservation of facial nerve function. METHOD: From January to November 2005, 19 patients with large acoustic neuroma were treated using intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation (TCEMEP) for preservation of facial nerve function. The relationship between the decrease of MEP amplitude after tumor removal and the postoperative function of the facial nerve was analyzed. RESULTS: MEP amplitude decreased more than 75% in 11 patients, of which 6 presented significant facial paralysis (H-B grade 3), and 5 had mild facial paralysis (H-B grade 2). In the other 8 patients, whose MEP amplitude decreased less than 75%, 1 experienced significant facial paralysis, 5 had mild facial paralysis, and 2 were normal. CONCLUSIONS: Intraoperative TCEMEP can be used to predict postoperative function of the facial nerve. The decreased MEP amplitude above 75 % is an alarm point for possible severe facial paralysis.

A Tortuous Process of Surgical Treatment for a Large Calcified Chronic Subdural Hematoma.

BACKGROUND: Calcified chronic subdural hematoma (CCSDH) is a rare disease for which no standard approach to treatment has been established. Reports covering both burr hole trepanation and craniotomy for CCSDH are rare. Furthermore, infection of CCSDH after the burr hole trepanation has not been reported in the literature. CASE DESCRIPTION: A 61-year-old man presented with left frontotemporoparietal CCSDH demonstrated on computed tomography (CT) scan. The patient underwent 2 separate burr hole trepanations with intraoperative irrigation and postoperative drainage. These procedures led to infection of the CCSDH. The patient eventually underwent an open craniotomy to provide complete removal of the hematoma. CONCLUSIONS: Owing to the complex contents of a CCSDH, burr hole trepanation cannot adequately drain the hematoma or relieve the mass effect. Craniotomy is a much more reliable approach for achieving complete resection of a CCSDH.

Protective Effects of Calpain Inhibition on Neurovascular Unit Injury through Downregulating Nuclear Factor-κB-related Inflammation during Traumatic Brain Injury in Mice.

BACKGROUND: In addition to neurons, all components of the neurovascular unit (NVU), such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury (TBI). Previous studies have shown that excessive stimulation of calpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact (CCI). METHODS: One hundred and eight mice were divided into three groups: the sham group, the control group, and the MDL28170 group. MDL28170 (20 mg/kg), an efficient calpain inhibitor, was administered intraperitoneally at 5 min, 3 h, and 6 h after experimental CCI. We then measured neurobehavioral deficits, calpain activity, inflammatory mediator levels, blood-brain barrier (BBB) disruption, and NVU deficits using electron microscopy and histopathological analysis at 6 h and 24 h after CCI. RESULTS: The MDL28170 treatment significantly reduced the extent of both cerebral contusion (MDL28170 vs. vehicle group, 16.90 ± 1.01 mm΃ and 17.20 ± 1.17 mm΃ vs. 9.30 ± 1.05 mm΃ and 9.90 ± 1.17 mm΃, both P < 0.001) and edema (MDL28170 vs. vehicle group, 80.76 ± 1.25% and 82.00 ± 1.84% vs. 82.55 ± 1.32% and 83.64 ± 1.25%, both P < 0.05), improved neurological scores (MDL28170 vs. vehicle group, 7.50 ± 0.45 and 6.33 ± 0.38 vs. 12.33 ± 0.48 and 11.67 ± 0.48, both P < 0.001), and attenuated NVU damage resulting (including tight junction (TJ), basement membrane, BBB, and neuron) from CCI at 6 h and 24 h. Moreover, MDL28170 markedly downregulated nuclear factor-κB-related inflammation (tumor necrosis factor-α [TNF-α]: MDL28170 vs. vehicle group, 1.15 ± 0.07 and 1.62 ± 0.08 vs. 1.59 ± 0.10 and 2.18 ± 0.10, both P < 0.001; inducible nitric oxide synthase: MDL28170 vs. vehicle group, 4.51 ± 0.23 vs. 6.23 ± 0.12, P < 0.001 at 24 h; intracellular adhesion molecule-1: MDL28170 vs. vehicle group, 1.45 ± 0.13 vs. 1.70 ± 0.12, P < 0.01 at 24 h) and lessened both myeloperoxidase activity (MDL28170 vs. vehicle group, 0.016 ± 0.001 and 0.016 ± 0.001 vs. 0.024 ± 0.001 and 0.023 ± 0.001, P < 0.001 and 0.01, respectively) and matrix metalloproteinase-9 (MMP-9) levels (MDL28170 vs. vehicle group, 0.87 ± 0.13 and 1.10 ± 0.10 vs. 1.17 ± 0.13 and 1.25 ± 0.12, P < 0.001 and 0.05, respectively) at 6 h and 24 h after CCI. CONCLUSIONS: These findings demonstrate that MDL28170 can protect the structure of the NVU by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and supporting the integrity of TJ during acute TBI.

Comparison between self-assembling peptide nanofiber scaffold (SAPNS) and fibrin sealant in neurosurgical hemostasis.

RADA16-I is a synthetic type I self-assembling peptide nanofiber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16-I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke inflammation in the surgically injured brain. We conducted an animal study to compare RADA16-I with fibrin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague-Dawley rats were randomized into three treatment groups: RADA16-I, fibrin sealant or gelatin sponge (control). Animals were sacrificed on day 3 and 42. Astrocytic and microglial infiltrations within the cerebral parenchyma adjacent to the operative site were significantly lower in the RADA16-I and fibrin sealant groups than control. RADA16-I did not cause more cellular inflammatory response despite its acidity when compared with fibrin sealant. Immunohistochemical studies showed infiltration by astrocytes and microglia into the fibrin sealant and RADA16-I grafts, suggesting their potential uses as tissue scaffolds. RADA16-I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofiber scaffold as well as drug and cell carrier.

[Precautionary study on acupuncture pretreatment for stroke at the early stage].

OBJECTIVE: To assess the clinical efficacy of acupuncture pretreatment for the prevention of stroke based on promoting the circulation of the Governor Vessel and regulating mentality, and explore its effect mechanism. METHODS: Seventy cases of transient ischemic attack (TIA) were randomized into an acupuncture group (35 cases) and a western medicine group (35 cases). In the acupuncture group, acupuncture therapy of promoting the circulation of the Governor Vessel and regulating mentality was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Shenzhu (GV 12), Dazhui (GV 14), Yamen (GV 15), Fengfu (GV 16), Baihui (GV 20) and Neck-Jiaji (EX-B 2). Acupuncture was given 6 times a week, at the interval of one day between two weeks. Totally, 21 days of treatment were taken as a session. In the western medicine group, aspirin enteric coated tablets were prescribed, 25 mg/tablet, 100 mg/day, once a night for oral administration, and 21 days of medication were taken as 1 session. There were 3 days at the interval between two sessions in each group and totally 2 sessions were required. Transcranial Doppler (TCD) was adopted before treatment and in two sessions of treatment to observe, mean flow velocity (Vm) of middle cerebral artery (MCA), vertebral artery (VA), basilar arte ry (BA) and pulsatility index (PI). The standard of the efficacy assessment of stroke aura was taken as the main efficacy index in the assessment of theraputic effect, the adverse reaction was observed. RESULTS: 1In TIA, MCA blood flow was accelerated in internal carotid system, and BA blood flow was accelerated in vertebral-basilar artery system. The treatments in the two groups enabled the blood flow in the responsible blood vessels slow down and the results in the acupuncture group L(60. 54+/-11.76)cm/s, (36. 17+/-8. 65)cm/s] were better than those in the western medicine group [(72. 34+/-9. 15)cm/s,(65. 23 +/-8. 99)cm/s] (P0. 05). CONCLUSION: Acupuncture intervention based on promoting the circulation of the Governor Vessel and regulating mentality achieves the superior efficacy on TIA and less adverse reactions as compared with aspirin. The effect mechanism is related potentially to the improvement of cerebral vascular hemodynamic.