Spontaneous brain activity in the hippocampal regions could characterize cognitive impairment in patients with Parkinson's disease.

OBJECTIVE: This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's disease (PD). METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) was performed on PD patients. The cognitive level of patients was assessed by the Montreal Cognitive Assessment (MoCA) scale. The fractional amplitude of low-frequency fluctuation (fALFF) was applied to measure the strength of spontaneous brain activity. Correlation analysis and between-group comparisons of fMRI data were conducted using Rest 1.8. By overlaying cognitively characterized brain regions and defining regions of interest (ROIs) based on their spatial distribution for subsequent cognitive stratification studies. RESULTS: A total of 58 PD patients were enrolled in this study. They were divided into three groups: normal cognition (NC) group (27 patients, average MoCA was 27.96), mild cognitive impairment (MCI) group (21 patients, average MoCA was 23.52), and severe cognitive impairment (SCI) group (10 patients, average MoCA was 17.3). It is noteworthy to mention that those within the SCI group exhibited the most advanced chronological age, with an average of 74.4 years, whereas the MCI group displayed a higher prevalence of male participants at 85.7%. It was found hippocampal regions were a stable representative brain region of cognition according to the correlation analysis between the fALFF of the whole brain and cognition, and the comparison of fALFF between different cognitive groups. The parahippocampal gyrus was the only region with statistically significant differences in fALFF among the three cognitive groups, and it was also the only brain region to identify MCI from NC, with an AUC of 0.673. The paracentral lobule, postcentral gyrus was the region that identified SCI from NC, with an AUC of 0.941. The midbrain, hippocampus, and parahippocampa gyrus was the region that identified SCI from MCI, with an AUC of 0.926. CONCLUSION: The parahippocampal gyrus was the potential brain region for recognizing cognitive impairment in PD, specifically for identifying MCI. Thus, the fALFF of parahippocampal gyrus is expected to contribute to future study as a multimodal fingerprint for early warning.

ISRIB improves white matter injury following TBI by inhibiting NCOA4-mediated ferritinophagy.

Traumatic brain injury (TBI) often results in persistent neurological dysfunction, which is closely associated with white matter injury. The mechanisms underlying white matter injury after TBI remain unclear. Ferritinophagy is a selective autophagic process that degrades ferritin and releases free iron, which may cause ferroptosis. Although ferroptosis has been demonstrated to be involved in TBI, it is unclear whether ferritinophagy triggers ferroptosis in TBI. Integrated stress response inhibitor (ISRIB) has neuroprotective properties. However, the effect of ISRIB on white matter after TBI remains uncertain. We aimed to investigate whether ferritinophagy was involved in white matter injury following TBI and whether ISRIB can mitigate white matter injury after TBI by inhibiting ferritinophagy. In this study, controlled cortical impact (CCI) was performed on rats to establish the TBI model. Ferritinophagy was measured by assessing the levels of nuclear receptor coactivator 4 (NCOA4), which regulates ferritinophagy, ferritin heavy chain 1(FTH1), LC3, ATG5, and FTH1 colocalization with LC3 in the white matter. Increased NCOA4 and decreased FTH1 were detected in our study. FTH1 colocalization with LC3 enhanced in the white matter after TBI, indicating that ferritinophagy was activated. Immunofluorescence co-localization results also suggested that ferritinophagy occurred in neurons and oligodendrocytes after TBI. Furthermore, ferroptosis was assessed by determining free iron content, MDA content, GSH content, and Perl's staining. The results showed that ferroptosis was suppressed by NCOA4 knockdown via shNCOA4 lentivirus infection, indicating that ferroptosis in TBI is triggered by ferritinophagy. Besides, NCOA4 deletion notably improved white matter injury following TBI, implying that ferritinophagy contributed to white matter injury. ISRIB treatment reduced the occurrence of ferritinophagy in neurons and oligodendrocytes, attenuated ferritinophagy-induced ferroptosis, and alleviated white matter injury. These findings suggest that NCOA4-mediated ferritinophagy is a critical mechanism underlying white matter injury after TBI. ISRIB holds promise as a therapeutic agent for this condition.

Predicting Hematoma Expansion and Prognosis in Cerebral Contusions: A Radiomics-Clinical Approach.

Hemorrhagic progression of contusion (HPC) often occurs early in cerebral contusions (CC) patients, significantly impacting their prognosis. It is vital to promptly assess HPC and predict outcomes for effective tailored interventions, thereby enhancing prognosis in CC patients. We utilized the Attention-3DUNet neural network to semi-automatically segment hematomas from computed tomography (CT) images of 452 CC patients, incorporating 695 hematomas. Subsequently, 1502 radiomic features were extracted from 358 hematomas in 261 patients. After a selection process, these features were used to calculate the radiomic signature (Radscore). The Radscore, along with clinical features such as medical history, physical examinations, laboratory results, and radiological findings, was employed to develop predictive models. For prognosis (discharge Glasgow Outcome Scale score), radiomic features of each hematoma were augmented and fused for correlation. We employed various machine learning methodologies to create both a combined model, integrating radiomics and clinical features, and a clinical-only model. Nomograms based on logistic regression were constructed to visually represent the predictive procedure, and external validation was performed on 170 patients from three additional centers. The results showed that for HPC, the combined model, incorporating hemoglobin levels, Rotterdam CT score of 3, multi-hematoma fuzzy sign, concurrent subdural hemorrhage, international normalized ratio, and Radscore, achieved area under the receiver operating characteristic curve (AUC) values of 0.848 and 0.836 in the test and external validation cohorts, respectively. The clinical model predicting prognosis, utilizing age, Abbreviated Injury Scale for the head, Glasgow Coma Scale Motor component, Glasgow Coma Scale Verbal component, albumin, and Radscore, attained AUC values of 0.846 and 0.803 in the test and external validation cohorts, respectively. Selected radiomic features indicated that irregularly shaped and highly heterogeneous hematomas increased the likelihood of HPC, while larger weighted axial lengths and lower densities of hematomas were associated with a higher risk of poor prognosis. Predictive models that combine radiomic and clinical features exhibit robust performance in forecasting HPC and the risk of poor prognosis in CC patients. Radiomic features complement clinical features in predicting HPC, although their ability to enhance the predictive accuracy of the clinical model for adverse prognosis is limited.

Association between the surgical approach and prognosis of spontaneous supratentorial deep intracerebral hemorrhage.

The association between surgical approach and prognosis in patients with spontaneous supratentorial deep intracerebral hemorrhage is unclear. We aimed to explore the association between surgical approach and prognosis in these patients. A retrospective cohort of 311 patients from 3 centers who were treated with surgery 24 h after ictus was recruited. The surgical procedure involved removing the intracerebral hematoma using an aspirator through either the cortical approach or Sylvian fissure approach, assisted by an endoscope or microscope. The primary outcome was the one-year modified Rankin scale (mRS) score. The association between the surgical approach and the one-year mRS score was explored by using ordinal logistic regression and binary logistic regression. Baseline characteristics were balanced by propensity score matching and inverse propensity score weighting. In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores when analyzed as an ordinal variable (3.00 [2.00-4.00] vs. 4.00 [3.00-5.00]; adjusted odds ratio, 3.15; 95% CI, 1.78-5.58; p < 0.001) and a dichotomous variable (74.14% vs. 49.01%; adjusted odds ratio, 6.61; 95% CI, 2.75-15.88; p < 0.001). Surgical approach was not significantly associated with rebleeding (p = 0.88) or three-month mortality (p = 0.81). In univariate analysis after propensity score matching, there were significant differences in one-year mRS score between the two groups (p < 0.001), and there were no significant differences in rebleeding (Fisher's exact test, p > 0.999) or three-month mortality (Fisher's exact test, p > 0.999). Inverse probability weighted regression analysis showed better one-year mRS scores when analyzed as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17-4.17; p < 0.001) and a dichotomous variable (adjusted odds ratio, 3.11; 95% CI, 2.16-4.77; p < 0.001) in the Sylvian fissure approach group; the surgical approach was not significantly associated with rebleeding (p = 0.50) or three-month mortality (p = 0.60). In the surgical treatment of patients with spontaneous supratentorial deep intracerebral hemorrhage, the Sylvian fissure approach may lead to a better functional outcome compared with the cortex approach. Future prospective studies are warranted to confirm this finding.

Deferoxamine reduces endothelial ferroptosis and protects cerebrovascular function after experimental traumatic brain injury.

Cerebrovascular dysfunction resulting from traumatic brain injury (TBI) significantly contributes to poor patient outcomes. Recent studies revealed the involvement of iron metabolism in neuronal survival, yet its effect on vasculature remains unclear. This study aims to explore the impact of endothelial ferroptosis on cerebrovascular function in TBI. A Controlled Cortical Impact (CCI) model was established in mice, resulting in a significant increase in iron-related proteins such as TfR1, FPN1, and FTH, as well as oxidative stress biomarker 4HNE. This was accompanied by a decline in expression of the ferroptosis inhibitor GPX4. Moreover, Perls' staining and nonhemin iron content assay showed iron overload in brain microvascular endothelial cells (BMECs) and the ipsilateral cortex. Immunofluorescence staining revealed more FTH-positive cerebral endothelial cells, consistent with impaired perfusion vessel density and cerebral blood flow. As a specific iron chelator, deferoxamine (DFO) treatment inhibited such ferroptotic proteins expression and the accumulation of lipid-reactive oxygen species following CCI, enhancing glutathione peroxidase (GPx) activity. DFO treatment significantly reduced iron deposition in BMECs and brain tissue, and increased density of the cerebral capillaries as well. Consequently, DFO treatment led to improvements in cerebral blood flow (as measured by laser speckle imaging) and behavioral performance (as measured by the neurological severity scores, rotarod test, and Morris water maze test). Taken together, our results indicated that TBI induces remarkable iron disorder and endothelial ferroptosis, and DFO treatment may help maintain iron homeostasis and protect vascular function. This may provide a novel therapeutic strategy to prevent cerebrovascular dysfunction following TBI.

Application of Skin-stretching Device for Closing Scalp Defect.

BACKGROUND: The scalp defect was a clinical common constructive challenge. This research verified the efficacy of the skin-stretching device in the treatment of scalp defect and assessed the associated complications. METHODS: The clinical data of 12 patients with scalp defect treated with skin-stretching device from January 2020 to January 2021 were collected. We used EASApprox skin-stretching device for the treatment of scalp defect. We described a detailed reconstruction procedure for this treatment. We collected the site, distance from wound edge and other characteristics of the wound, and recorded the number of stretching cycles, operation time, closed state, healing time, and observed postoperative complications and wound healing status. RESULTS: In this research, the scalp defect was mainly caused by pressure ulcer, and mainly located in the parietooccipital site. The average distance from wound edge was 3.2 cm, the average stretching cycles was 4.2 times during the operation, and the average operation time was 43.5 minutes. Ten patients were directly sutured after stretching, and 2 patients underwent first-stage stretching to reduce the wound. The average time of wound healing was 13.5 days. Postoperative follow-up of 3 months, no patients had wound tear, necrosis, 1 patient suffered from wound exudation and infection due to poor nutrition. Skin function and final scar was acceptable. CONCLUSION: The treatment of skin-stretching device was effective for scalp defect and has the advantages of convenient operation, acceptable functional results, without severe complications. In addition to traditional treatment, this was a promising treatment. However, more clinical and preclinical research of the skin-stretching device were required.

Effect of hypophosphatemia on prognosis after spontaneous intracerebral hemorrhage: a retrospective study.

OBJECTIVE: Hypophosphatemia often occurs after spontaneous intracerebral hemorrhage, but the effect of hypophosphatemia on its prognosis is under debate. METHODS: Clinical data of patients with spontaneous intracerebral hemorrhage admitted to our neurosurgery department from January 2018 to June 2020 were retrospectively analyzed. The patients were divided into the hypophosphatemia group and the nonhypophosphatemia group according to the serum phosphorus test values obtained three times within 1 week after admission. The incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score were compared between the two groups. The influence of low phosphorus in patients with hypophosphatemia on the 6-month mRS score was explored. RESULTS: A total of 133 patients were included, of which 85 had hypophosphatemia. Forty-two patients (21 in the hypophosphatemia group and 21 in the nonhypophosphatemia group) were enrolled after propensity score matching. There were no statistically significant differences in the incidence of complications during hospitalization, 28-day mortality, and 6-month mRS score between the two groups (P > 0.05). In 85 patients with hypophosphatemia, the minimum serum phosphorus was associated with the 6-month mRS score (B = - 3.153, 95% CI: - 5.842 ~ - 0.463, P = 0.022). The cutoff value of serumphosphorus for predicting 6-month mRS score was 0.505 mmol/l. CONCLUSION: Whether hypophosphatemia occurred during hospitalization in patients with spontaneous intracerebral hemorrhage showed no effect on the incidence of complications, 28-day mortality, and 6-month mRS score. A significant decrease in serum phosphorus during hospitalization (≤ 0.505 mmol/l) might correlate with a poor 6-month mRS score. Maintaining serum phosphorus stability after spontaneous intracerebral hemorrhage may improve prognosis.

Management of Primary Brainstem Hemorrhage: A Review of Outcome Prediction, Surgical Treatment, and Animal Model.

Primary brainstem hemorrhage (PBH) has the worst prognosis of all types of intracerebral hemorrhage. Currently, the management of PBH is controversial. Hematoma classification, scoring systems, and electrophysiological monitoring are critical for predicting the outcome of PBH. Surgery may be an effective treatment for PBH. Clinical studies have emphasized the importance of animal models for understanding the pathogenesis and pathological mechanisms of PBH. In this study, combined with recent studies, the outcome prediction, surgical treatment, and animal models of PBH were reviewed.

Clemastine Promotes Differentiation of Oligodendrocyte Progenitor Cells Through the Activation of ERK1/2 via Muscarinic Receptors After Spinal Cord Injury.

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery.

PTEN and AKT/GSK-3ß/CRMP-2 signaling pathway are involved in neuronal apoptosis and axonal injury in early brain injury after SAH in rats.

In early brain injury (EBI) after subarachnoid hemorrhage (SAH), white matter (WM) axonal injury plays a key role in the prognosis of the disease. The purpose of this study was to investigate the effects of phosphatase and tensin homolog deleted on chromosome ten (PTEN) on axonal injury and neuronal apoptosis post-SAH in rats and to find its underlying mechanism. Adeno-associated virus was injected into the lateral ventricle to suppress or promote PTEN. Neural function post-SAH in animals was determined by the modified Garcia score, beam balance, and Rotarod test, and the blood-brain barrier disruption was assessed by the brain water content. Axonal injury post-SAH was observed by TEM and determined by IF, and neuron apoptosis was measured by TUNEL staining. The mechanism was analyzed by Western blot to detect p-PTEN/PTEN, p-AKT/AKT, p-GSK-3ß/GSK-3ß, p-CRMP-2/CRMP-2, axonal injury marker ß-APP and pro- and anti-apoptosis proteins, including Bax and Bcl-2, expression. We found 1. After knocking down PTEN, neuronal apoptosis and axonal injury were alleviated, and nerve function and blood-brain barrier were protected; accordingly, after overexpression of PTEN, neuronal apoptosis and axon damage were aggravated, and nerve function damage and blood-brain barrier damage were increased. 2. PTEN and AKT/GSK-3ß/CRMP-2 pathway were jointly involved in regulating neuronal apoptosis and WM axon injury after SAH. According to our research, PTEN was a negative factor of EBI, and together with the AKT/GSK-3ß/CRMP-2 signaling pathway aggravates neuronal apoptosis and WM axon damage after SAH. Inhibition of PTEN expression may become a new target for SAH treatment.

Clemastine Enhances Myelination, Delays Axonal Loss and Promotes Functional Recovery in Spinal Cord Injury.

Recent evidence has shown that demyelination occurs along with axonal degeneration in spinal cord injury (SCI) during the secondary injury phase. Oligodendrocyte precursor cells (OPC) are present in the lesions but fail to differentiate into mature oligodendrocytes and form new myelin. Given the limited recovery of neuronal functions after SCI in adults without effective treatment available so far, it remains unknown whether enhancing OPC differentiation and myelination could benefit the recovery of SCI. To show the significance of myelin regeneration after SCI, the injury was treated with clemastine in the rat model. Clemastine is an FDA-approved drug that is potent in promoting oligodendrocyte differentiation and myelination in vivo, for four weeks following SCI. Motor function was assessed using sloping boards and grid walking tests and scored according to the Basso, Beattie, and Bresnahan protocol. The myelin integrity and protein expression were evaluated using transmission electron microscopy and immunofluorescence, respectively. The results indicated that clemastine treatment preserves myelin integrity, decreases loss of axons and improves functional recovery in the rat SCI model. The presented data suggest that myelination-enhancing strategies may serve as a potential therapeutic approach for the functional recovery in SCI.

Ferritinophagy is Involved in Experimental Subarachnoid Hemorrhage-Induced Neuronal Ferroptosis.

Ferroptosis is a novel form of regulated cell death involved in the pathophysiological process of experimental subarachnoid hemorrhage (SAH), but how neuronal ferroptosis occurs remains unknown. In this study, we report that SAH-induced ferroptosis is macroautophagy/autophagy dependent because the inhibition of autophagy by knocking out autophagy-related gene 5 (ATG5) apparently mitigated SAH-induced ferroptosis. We created an experimental SAH model in Sprague-Dawley rats to determine the possible mechanism. We found that SAH can trigger neuronal ferroptosis, as evidenced by the disruption of iron homeostasis, elevation of intracellular lipid peroxidation (LPO) and decreased expression of ferroptosis-protective proteins. Then, we inhibited autophagy by ATG5 gene knockout, showing that autophagy inhibition can reduce the intracellular iron level and LPO, improve the expression of ferroptosis-protective proteins, and subsequently alleviate SAH-induced cell death. Additionally, autophagy inhibition also attenuated SAH prognostic indicators, such as brain edema, blood-brain barrier permeability, and neurological deficits. These findings not only present an opinion that SAH triggers neuronal ferroptosis via activation of ferritinophagy but also indicate that regulating ferritinophagy and maintaining iron homeostasis could provide clues for the prevention of early brain injury.

Analysis of Clinical Characteristics and Prognosis of Traumatic Brain Injury in Papua New Guinea.

OBJECTIVE: To evaluate the clinical characteristics and prognosis of TBI patients from 2016 to 2019 admitted to Port Moresby General Hospital (PMGH) of Papua New Guinea (PNG) and compare the results with previous researches to analyze current clinical characteristics and prognosis. METHODS: A retrospective study was performed on 389 TBI patients in Port Moresby General Hospital (PMGH) over a 48-month period (from January 2016 to December 2019). The clinical and radiographic data were collected. Patients were followed up for at least 3 months, and outcomes were assessed using the Glasgow Outcome Scale (GOS). Univariate and multivariate logistic regressions were performed to analyze the prognosis and intracranial infection of patients, as well as the effect of surgery on the prognosis of TBI patients. RESULTS: The average age of the 389 TBI patients was 24.9 years old, and the most common age was 18-40 years old, accounting for 55.5%. The proportion of male patients was 79.4%, and the proportion of juvenile patients (≤18 years) was 30.8%. The most primary cause of injury was fighting and brawling (38.0%). At admission, patients had an average GCS score of 9.1, and patients with severe TBI accounted for 46.8%. Overall, 32.1% of the patients had a good prognosis, with a mortality rate of 13.9% (54 cases). Analyzing the relationship between surgical treatment and prognosis in 303 patients with moderate or severe TBI, there was no statistical significance. Univariate and logistic regression analyses for poor prognosis included gender, GCS, multiple injuries, Rotterdam CT scores, and intracranial infection. Univariate and logistic regression analyses for intracranial infection included GCS, open brain trauma, and postoperative drainage time. CONCLUSION: Despite there has been a secular trend towards reduced incidence of TBI, the prognosis of moderate or severe TBI patients who received surgery showed no significant improvement, indicating that PNG, as a backward developing country, faced a huge problem in TBI prevention and control.

5-Lipoxygenase inhibition reduces inflammation and neuronal apoptosis via AKT signaling after subarachnoid hemorrhage in rats.

Early brain injury (EBI) is a major contributor to the high mortality and morbidity after subarachnoid hemorrhage (SAH). Inflammatory responses and neuronal apoptosis are important causes of EBI. Because 5- lipoxygenase (5-LOX) is known to be involved various central nervous system diseases, we investigated the effects of 5-LOX inhibition during EBI after SAH. Zileuton and LY294002 were used to inhibit expression of 5-LOX and Akt, respectively. We found that 5-LOX expression was significantly increased in the cytoplasm of cortical neurons after SAH and was accompanied by upregulated expression of the inflammatory factors LTB4, TNF-α, IL-1ß and IL-6; upregulation of the pro-apoptotic factor Bax; downregulation of the anti-apoptotic factor Bcl-2; and an increased apoptosis rate. Gastric Zileuton administration significantly suppressed all of those effects and improved neurological function. Zileuton also upregulated activated (phosphorylated) AKT levels, and these beneficial effects of Zileuton were abolished by intracerebroventricular infusion of the PI3K inhibitor LY294002. Taken together, these findings indicate that 5-LOX mediates pro-inflammatory and pro-apoptotic effects that contribute to EBI after SAH and that those effects are suppressed by activation of PI3K/Akt signaling. This suggests targeting 5-LOX may be an effective approach to treating EBI after SAH.

Wearable Mixed-Reality Holographic Navigation Guiding the Management of Penetrating Intracranial Injury Caused by a Nail.

Penetrating brain injury caused by a nail is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons. Nail entering the brain from the orbit and lodging within the cranial cavity is even more unusual. A 53-year-old male was found unconscious at a construction site, and brain CT revealed not only the presence of a nail beneath the inner table of the parietal bone, but also traumatic intracerebral hematoma. Consequently, accurate localization of the nail and hematoma was mandatory for surgical plan. During surgical planning, computational model reconstruction and trajectory calculation were completed using preoperative CT in 3D Slicer. Under the guidance of a head-mounted mixed-reality holographic computer, the neurosurgeon was able to visualize and interact with the hologram of the surgical plan, and intraoperative findings demonstrated that our low-cost portable wearable mixed-reality holographic navigation assisted precise localization of the nail and intracerebral hematoma, assuring less injury to the already compromised brain. After the surgery, the patient could obey commands, and postoperative imaging ruled out the possibility of brain abscess during follow-up. To the best of our knowledge, this is the first report on using a low-cost wearable mixed-reality holographic navigation to guide the management of penetrating intracranial injury caused by a nail.

Intranasal delivery of Paclitaxel encapsulated nanoparticles for brain injury due to Glioblastoma.

Brain injury is a common cause for physical and emotional effects to the large number of populations. Moreover, glioblastoma is the tumor in brain with no possible treatment leading to death. The blood-brain barrier's makes the treatment more difficult by preventing the drugs to reach central nervous system. Paclitaxel (PTX) encapsulated Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), PTX-PLGA-NPs were developed using emulsification method. The PTX-PLGA-NPs were characterized using Malvern Zetasizer and Scanning Electron Microscopy and were evaluated for their cytotoxicity in U87MG cells. PTX-PLGA-NPs were prepared using single emulsion method having size of 154 ± 22.19 nm with zeta potential of -23.7 mV. The PTX-PLGA-NPs were spherical in shape and have dose dependent cytotoxicity on U87MG cells. The PTX was released from the particles with initial burst release followed by sustained release pattern. The biodistribution was studied in mice with glioblastoma model using 125I radiolabeled PTX-PLGA-NPs and anti-glioblastoma was studied with PTX-PLGA-NPs. The biodistribution studies revealed PTX-PLGA-NPs after intranasal administration resulted in higher in vivo uptake with high anti-glioblastoma efficacy. The results suggest that PTX-PLGA-NPs administered through intranasal route have potential in the treatment of glioblastoma.

Perioperative management strategy of severe traumatic brain injury during the outbreak of COVID-19.

Since December 2019, a pneumonia caused by a new coronavirus, i.e. COVID-19 occurred in Wuhan, Hubei Province, China. Although the epidemic in China has been bought under control, the global COVID-19 situation is still grim. Severe traumatic brain injury (TBI), as one of critical conditions in the department of neurosurgery, requires an early and effective treatment, especially surgery. There were currently no reliable guidelines on how to perform perioperative protection in TBI patients with suspected or confirmed coronavirus infection. According to the corresponding treatment regulations and guidelines issued by the authorities, we summarized the management strategy of TBI patients in perioperative period during the COVID-19 outbreak based on medical and nursing practice, in order to provide a reference for clinicians.

Construction and expression of recombinant uricase­expressing genetically engineered bacteria and its application in rat model of hyperuricemia.

At present, the treatment of hyperuricemia is designed primarily to decrease the production of uric acid using xanthine oxidase inhibitors; however, the therapeutic effect is not satisfactory. Therefore, the key to the successful treatment of hyperuricemia is to increase the excretion of uric acid. The aim of present study was to construct uricase­expressing genetically engineered bacteria and analyze the effects of these engineered bacteria on the lowering of uric acid levels in a rat model of hyperuricemia. The uricase expression vector was constructed by gene recombination technology and transfected into Escherichia coli. The expression and activity of uricase were analyzed by SDS­PAGE analysis and Bradford assay. The water consumption, food intake, body weight, eosinophil count and intestinal histology, in addition to the levels of serum uric acid (SUA) and allantoin in the feces of the rats, were assessed. The intestinal contents of the rats were analyzed by 16S rDNA sequencing technology. The results demonstrated that uricase­expressing genetically engineered bacteria secreted active uricase. All rats exhibited a natural growth trend during the entire experiment, and the SUA of hyperuricemic rats treated with uricase­expressing engineered bacteria was significantly decreased. In conclusion, these results indicate that uricase secreted by recombinant uricase­expressing genetically engineered bacteria served an important role in decreasing SUA levels in a rat model of hyperuricemia.

Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway.

Traumatic brain injury (TBI) is the major cause of high mortality and disability rates worldwide. Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma (PPARγ) that can reduce inflammation following TBI. Clinically, neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPARγ in TBI animals, only few could be converted into clinical, since TBI mechanisms in humans and animals are not completely consistent. The present study, provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI. First, we detected interleukin-6 (IL-6), nitric oxide (NO) and Caspase-3 in TBI clinical specimens, confirming a presence of a high expression of inflammatory factors. Western blot (WB), quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect PPARγ, IL-6, and p-NF-κB to identify the mechanisms of neuroinflammation. Then, in the rat TBI model, neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPARγ activator) or T0070907 (PPARγ inhibitor), and PPARγ, IL-6 and p-NF-κB were detected again by qRT-PCR, WB and immunofluorescence (IF). The obtained results revealed that: 1) increased expression of IL-6, NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI, and decreased PPARγ in brain tissue; 2) pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI; 3) the protective effect of pioglitazone was achieved by activating PPARγ and reducing NF-κB and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-κB/IL-6 pathway.

Basic Fibroblast Growth Factor (bFGF) Protects the Blood-Brain Barrier by Binding of FGFR1 and Activating the ERK Signaling Pathway After Intra-Abdominal Hypertension and Traumatic Brain Injury.

BACKGROUND Intra-abdominal hypertension (IAH) is associated with high morbidity and mortality. IAH leads to intra-abdominal tissue damage and causes dysfunction in distal organs such as the brain. The effect of a combined injury due to IAH and traumatic brain injury (TBI) on the integrity of the blood-brain barrier (BBB) has not been investigated. MATERIAL AND METHODS Intracranial pressure (ICP) monitoring, brain water content, EB permeability detection, immunofluorescence staining, real-time PCR, and Western blot analysis were used to examine the effects of IAH and TBI on the BBB in rats, and to characterize the protective effects of basic fibroblast growth factor (bFGF) on combined injury-induced BBB damage. RESULTS Combined injury from IAH and TBI to the BBB resulted in brain edema and increased intracranial pressure. The effects of bFGF on alleviating the rat BBB injuries were determined, indicating that bFGF regulated the expression levels of the tight junction (TJ), adhesion junction (AJ), matrix metalloproteinase (MMP), and IL-1ß, as well as reduced BBB permeability, brain edema, and intracranial pressure. Moreover, the FGFR1 antagonist PD 173074 and the ERK antagonist PD 98059 decreased the protective effects of bFGF. CONCLUSIONS bFGF effectively protected the BBB from damage caused by combined injury from IAH and TBI, and binding of FGFR1 and activation of the ERK signaling pathway was involved in these effects.