Prognostic Value of Different Computed Tomography Scoring Systems in Patients With Severe Traumatic Brain Injury Undergoing Decompressive Craniectomy.

OBJECTIVE: In this study, we investigate the preoperative and postoperative computed tomography (CT) scores in severe traumatic brain injury (TBI) patients undergoing decompressive craniectomy (DC) and compare their predictive accuracy. METHODS: Univariate and multivariate logistic regression analyses were used to determine the relationship between CT score (preoperative and postoperative) and mortality at 30 days after injury. The discriminatory power of preoperative and postoperative CT score was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Multivariate logistic regression analysis adjusted for the established predictors of TBI outcomes showed that preoperative Rotterdam CT score (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.13-11.50; P = 0.030), postoperative Rotterdam CT score (OR, 4.17; 95% CI, 1.63-10.66; P = 0.003), preoperative Stockholm CT score (OR, 3.41; 95% CI, 1.42-8.18; P = 0.006), postoperative Stockholm CT score (OR, 4.50; 95% CI, 1.60-12.64; P = 0.004), preoperative Helsinki CT score (OR, 1.44; 95% CI, 1.03-2.02; P = 0.031), and postoperative Helsinki CT score (OR, 2.55; 95% CI, 1.32-4.95; P = 0.005) were significantly associated with mortality. The performance of the postoperative Rotterdam CT score was superior to the preoperative Rotterdam CT score (AUC, 0.82-0.97 vs 0.71-0.91). The postoperative Stockholm CT score was superior to the preoperative Stockholm CT score (AUC, 0.76-0.94 vs 0.72-0.92). The postoperative Helsinki CT score was superior to the preoperative Helsinki CT score (AUC, 0.88-0.99 vs 0.65-0.87). CONCLUSIONS: In conclusion, assessing the CT score before and after DC may be more precise and efficient for predicting early mortality in severe TBI patients who undergo DC.

Effect of α7nAChR on learning and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Inhibition of miRNA-21 promotes retinal ganglion cell survival and visual function by modulating Müller cell gliosis after optic nerve crush.

BACKGROUND: Müller cell gliosis not only plays an important physiological role by maintaining retinal neuronal homeostasis but is also associated with multiple pathological events in the retina, including optic nerve crush (ONC) injury. Modulating Müller cell gliosis contributes to the creation of a permissive environment for neuronal survival. However, the underlying mechanism of Müller cell gliosis has remained elusive. OBJECTIVE: To investigate the underlying mechanism of Müller cell gliosis after ONC. METHODS: Rats with ONC injury were transfected with miRNA-21 (miR-21) agomir (overexpressing miR-21) or antagomir (inhibiting miR-21) via intravitreous injection. Immunofluorescence and western blotting were performed to confirm the effects of miR-21 on Müller cell gliosis. The retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography and the positive scotopic threshold response (pSTR) was recorded using electroretinogram. RESULTS: In the acute phase (14 days) after ONC, compared with the crushed group, inhibiting miR-21 promoted Müller cell gliosis, exhibiting thicker processes and increased GFAP expression. In the chronic phase (35 days), inhibiting miR-21 ameliorated Müller cell gliosis, which exhibited thicker and denser processes and increased GFAP expression. Retinal ganglion cell (RGC) counts in retinas showed that the number of surviving RGCs increased significantly in the antagomir group. The thickness of the RNFL increased significantly, and pSTR showed significant preservation of the amplitudes in the antagomir group. CONCLUSIONS: Inhibition of miR-21 promotes RGC survival, RNFL thickness and the recovery of RGC function by modulating Müller cell gliosis after ONC.

Take it seriously or not: postoperative pneumocephalus in CSDH patients?

Background: Pneumocephalus is a common finding after burr-hole drainage of chronic subdural hematoma (CSDH). Its effects have not been specifically studied.Methods: A retrospective analysis was performed in 140 patients with CSDH with single burr-hole drainage. The pre- and postoperative volumes of intracranial hematoma and the postoperative volume of pneumocephalus were calculated and analyzed with their relationships with Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores.Results: The preoperative hematoma volume and the patient ages are positively correlated with the 1-day postoperative pneumocephalus volume (p < 0.001, p < 0.01). There is no correlation between postoperative pneumocephalus volume and GCS/GOS scores (p > 0.05) and there is no difference of GCS/GOS scores or CSDH recurrence rate between patients with and without pneumocephalus (p > 0.05). The age and the volume of 1-day postoperative pneumocephalus are positively correlated with the absorbing rate of pneumocephalus (p < 0.01, p < 0.001).Conclusions: The pneumocephalus at a certain range has no effect on the prognosis of patients with CSDH and requires no specific intervention due to its self-absorbing capacity in the normal progress after surgery.HighlightsNo correlation between postoperative pneumocephalus volume and GCS/GOS scores.No difference of GCS/GOS or recurrence between patients with pneumocephalus or not.Pneumocephalus at certain range has no effect on the prognosis of patients.

Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth.

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.

Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma.

Previous study revealed that higher expression of transforming growth factor beta induced (TGFBI) is correlated to poorer cancer-specific survival and higher proportion of tumor necrosis and Fuhrman grades III and IV in clear cell renal cell carcinomas. However, the relationships between TGFBI expression and malignant phenotypes of gliomas remain unclear. We downloaded and analyzed data from seven GEO datasets (GSE68848, GSE4290, GSE13041, GSE4271, GSE83300, GSE34824 and GSE84010), the TCGA database and the REMBRANDT database to investigate whether TGFBI could be a biomarker of glioma. From microarray data (GSE68848, GSE4290) and RNA-seq data (TCGA), TGFBI expression levels were observed to correlate positively with pathological grade, and TGFBI expression levels were significantly higher in gliomas than in normal brain tissues. Furthermore, in GSE13041, GSE4271 and the TCGA cohort, TGFBI expression in the mesenchymal (Mes) subtype high-grade glioma (HGG) was significantly higher than that in the proneural subtype. Kaplan-Meier survival analysis of GBM patients in the GSE83300 dataset, REMBRANDT and TCGA cohort revealed that patients in the top 50% TGFBI expression group survived for markedly shorter periods than those in the bottom 50%. Analysis of grade III gliomas showed that the median survival time was significantly shorter in the TGFBI high expression group than in the TGFBI low expression group. In addition, we found that TGFBI expression levels might relate to several classical molecular characterizations of glioma, such as, IDH mutation, TP53 mutation, EGFR amplification, etc. These results suggest that TGFBI expression positively correlates with glioma pathological grades and that TGFBI is a potential signature gene for Mes subtype HGG and a potential prognostic molecule.

Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases.

The Rho family of small GTPases was considered as molecular switches in regulating multiple cellular events, including cytoskeleton reorganization. The Rho GTPase-activating proteins (RhoGAPs) are one of the major families of Rho GTPase regulators. RhoGAPs were initially considered negative mediators of Rho signaling pathways via their GAP domain. Recent studies have demonstrated that RhoGAPs also regulate numerous aspects of neuronal development and are related to various neurodegenerative diseases in GAP-dependent and GAP-independent manners. Moreover, RhoGAPs are regulated through various mechanisms, such as phosphorylation. To date, approximately 70 RhoGAPs have been identified; however, only a small portion has been thoroughly investigated. Thus, the characterization of important RhoGAPs in the central nervous system is crucial to understand their spatiotemporal role during different stages of neuronal development. In this review, we summarize the current knowledge of RhoGAPs in the brain with an emphasis on their molecular function, regulation mechanism and disease implications in the central nervous system.

Biomarkers of cognitive dysfunction in traumatic brain injury.

Acetylcholine, glutamate, dopamine, serotonin (5-HT), gamma-aminobutyric acid, substance P (SP), amyloid-ß (Aß) and neurotrophic protein S100B are arguably the most important cognition-related biomarkers in the brain. Among this list are five neurotransmitters that signal through postsynaptic receptors. Our knowledge of cognition-related biomarkers has been advanced through translational experiments and clinical case-study data. Although these biomarkers are widespread in the brain and pronounced individual variations exist, these biomarkers can be used to identify both acute and chronic abnormalities following traumatic brain injury. Changes in these biomarkers likely indicate damage to brain networks or to key brain cell types that support cognitive functions. Identification of such biomarker abnormalities could result in earlier diagnoses, improved prognoses and therapies that enable neurotransmitters to return to normal levels.

Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells.

Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 µM) for 24h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.

Role of Extradural Clinoidectomy and Optic Unroofing in Resection of an Anterior Clinoidal Meningioma with Encasement of the Internal Carotid Artery and Its Branches.

Anterior clinoidal meningiomas (ACMs) remain a major neurosurgical challenge. The skull base techniques, including extradural clinoidectomy and optic unroofing performed at the early stage of surgery, provide advantages for improving the extent of resection, and thereby enhancing overall outcome, and particularly visual function. Additionally, when the anterior clinoidal meningiomas encase neurovascular structures, particularly the supraclinoid internal carotid artery and its branches, this further increases morbidity and decreases the extent of resection. Although it might be possible to remove the tumor from the artery wall despite complete encasement or narrowing, the decision of whether the tumor can be safely separated from the arterial wall ultimately must be made intraoperatively. The patient is a 75-year-old woman with right-sided progressive vision loss. In the neurological examination, she only had light perception in the right eye without any visual acuity or peripheral loss in the left eye. MRI showed a homogeneously enhancing right-sided anterior clinoidal mass with encasing and narrowing of the supraclinoid internal carotid artery (ICA). Computed tomography (CT) angiography showed a mild narrowing of the right supraclinoid ICA with associated a 360-degree encasement. The decision was made to proceed using a pterional approach with extradural anterior clinoidectomy and optic unroofing. The surgery and postoperative course were uneventful. MRI confirmed gross total resection ( Figs. 1 and 2 ). The histopathology was a meningothelial meningioma, World Health Organization (WHO) grade I. The patient continues to do well without any recurrence and has shown improved vision at 15-month follow-up. This video demonstrates important steps of the microsurgical skull base techniques for resection of these challenging tumors. The link to the video can be found at https://youtu.be/vt3o1c2o8Z0.

Safety and efficacy of microsurgery for complex cranial pathologies in the ultra-geriatric population.

OBJECTIVE: The global increase in the "ultra-geriatric" population (aged 80 years and older) has led to higher demand for neurosurgical procedures in this vulnerable population. The objective was to evaluate the safety and efficacy of advanced microsurgical procedures on ultra-geriatric patients, in our modern era of neurosurgery, anesthesiology, and advanced medical care. METHODS: The study examined 66 complex cranial procedures, performed on 65 ultra-geriatric patients, who constituted 3.8% of the 4461 consecutive neurosurgical procedures performed by a single neurosurgeon over 14-years in a tertiary care university hospital. Excluded from this study were intra- or extra-axial spontaneous hematomas or traumatic brain injuries, infections, biopsy-only cases and carotid endarterectomies. RESULTS: The most common indication for surgery for the 66 complex cranial procedures were meningiomas (23.9%), followed by gliomas (17.9%), and metastatic brain tumors (17.9%). Postoperative complications occurred in seven procedures (10.60%). No patient deaths were directly caused by intra- or postoperative events, and only one 30-day mortality occurred. All deceased patients had a statistically significant higher American Society of Anesthesiologists (ASA) class (p = 0.024). However, there was no significant correlation between ASA class and modified Rankin scale at discharge (p = 0.238). CONCLUSION: With the aging global population and increasing life expectancy, the number of ultra-geriatric patients with complex pathologies seeking advanced microsurgical treatment is growing. Therefore, neurosurgeons are confronting a growing number and variety of complex pathologies in ultra-geriatric patients in their daily practice. Regardless of advanced age, microsurgery provides safe and effective treatment, with age alone not being a barrier to proper neurosurgical treatment when other risk factors are adequately modified.

Maf1 regulates axonal regeneration of retinal ganglion cells after injury.

Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.

The efficacy of paxlovid in elderly patients infected with SARS-CoV-2 omicron variants: Results of a non-randomized clinical trial.

Objective: To evaluate the efficacy of Paxlovid in treating Chinese elder patients infected with SARS-CoV-2 omicron variants. Materials and methods: We performed a non-randomized, controlled trial in Shanghai, China. Participants infected with SARS-CoV-2 omicron variants were enrolled. All patients were divided into the Paxlovid group or the control group according to the Chinese guideline (version 9). The nucleic acid shedding time was the primary endpoint. Results: According to the inclusion criteria, 142 patients infected with omicron variants were enrolled, 36 patients who did not receive paxlovid were assigned to the control group, and 106 were in the Paxlovid group. The baseline characteristics were similar in either group. No significant difference in BMI, age, time from onset to patient enrollment, the severity on first admission, vaccination status, comorbidity, first symptoms, and laboratory results were recorded. Compared to the control group, participants in the Paxlovid group had a shorter viral shedding time [11.11 (2.67) vs. 9.32 (2.78), P = 0.001]. Conclusion: In Chinese elder patients infected with the variant of SARS-CoV-2 omicron, our data suggest that Paxlovid can significantly reduce the nucleic acid shedding time.

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2.

Background: This study explores the risk factors associated with viral shedding time in elderly Chinese patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron. Methods: Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to shedding time (≥10 days, "late clearance group" and <10 days, "early clearance group"). Results: A total of 180 patients were enrolled in the study (88 early, 92 late), with a median viral shedding time of 10 days and a mean age of 77.02 years. Prolonged SARS-CoV-2 omicron shedding was associated with old age (p = 0.007), lack of vaccination (p = 0.001), delayed admission to hospital after onset of diagnosis (p = 0.001), D-dimer (p = 0.003), and methylprednisolone treatment (p = 0.048). In multivariate analysis, vaccination (OR, 0.319, 95% CI, 0.130-0.786, p = 0.013), Paxlovid (OR, 0.259, 95% CI, 0.104-0.643, p = 0.004), and time from onset of diagnosis to admission (OR, 1.802, 95% CI, 1.391-2.355, p = 0.000) were significantly associated with viral clearance. Conclusions: Time from onset of diagnosis to hospitalization, lack of treatment with Paxlovid, and lack of vaccination were independent risk factors in elderly Chinese patients infected with SARS-CoV-2 omicron for prolonged viral shedding.

CRMP2 improves memory deficits by enhancing the maturation of neuronal dendritic spines after traumatic brain injury.

Our recent study investigated the role of collapsin response mediator protein-2 (CRMP2) on dendritic spine morphology and memory function after traumatic brain injury (TBI). First, we examined the density and morphology of dendritic spines in Thy1-GFP mice on the 1 st day (P1D) and 7th day (P7D) after controlled cortical impact injury (CCI). The dendritic spine density in the hippocampus was decreased on P1D, in which mainly mushroom-type and thin-type spines were lost. The density of dendritic spines was increased on P7D, most of which were of the thin type. Next, we explored the expression of CRMP2 on P1D and P7D. CRMP2 expression was decreased on P1D, but the levels of the CRMP2 breakdown product were increased. On P7D, the expression pattern was the opposite. Then, we constructed CRMP2 overexpression and knockdown plasmids and transfected them into cultured neurons in vitro. CRMP2 increased the dendritic spine density of cultured neurons and the proportion of mushroom-type spines, while CRMP2-shRNA reduced the dendritic spine density and the proportion of mushroom-type spines. To determine the role of CRMP2 in dendritic spines after TBI, we stereotactically injected the CRMP2 overexpression and knockdown viruses into the hippocampus and found that CRMP2 increased the dendritic spine density and the proportion of mushroom-type spines after TBI. Meanwhile, as suggested by the morphological changes, fear conditioning behavioral experiments confirmed that CRMP2 improved memory deficits after TBI.

4-Phenylbutyrate Ameliorates Anxiety Disorder by Inhibiting Endoplasmic Reticulum Stress after Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is accompanied frequently by adverse sequelae and psychiatric disorders, such as anxiety, leading to a decreased quality of life, social isolation, and poor outcomes in patients. The mechanisms regulating psychiatric disorders post-DAI are not well elucidated, however. Previous studies showed that endoplasmic reticulum (ER) stress functions as a pivotal factor in neurodegeneration disease. In this study, we showed that DAI can trigger ER stress and unfolded protein response (UPR) activation in both the acute and chronic periods, leading to cell death and anxiety disorder. Treatment with 4-phenylbutyrate (4-PBA) is able to inhibit the UPR and cell apoptosis and relieve the anxiety disorder in our DAI model. Later (14 days post-DAI) 4-PBA treatment, however, can restore only the related gene expression of ER stress and UPR but not the psychiatric disorder. Therefore, the early (5 min after DAI) administration of 4-PBA might be a therapeutic approach for blocking the ER stress/UPR-induced cell death and anxiety disorder after DAI.

Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush.

Optic nerve injury is a leading cause of irreversible visual impairment worldwide and can even cause blindness. Excessive activation of astrocytes has negative effects on the repair and recovery of retinal ganglion cells following optic nerve injury. However, the molecular and cellular mechanisms underlying astrocyte activation after optic nerve injury remain largely unknown. In the present study, we explored the effects of microRNA-21 (miR-21) on axon regeneration and flash visual evoked potential (F-VEP) and the underlying mechanisms of these effects based on astrocyte activation in the rat model of optic nerve crush (ONC). To the best of our knowledge, this article is the first to report that inhibition of miR-21 enhances axonal regeneration and promotes functional recovery in F-VEP in the rat model of ONC. Furthermore, inhibition of miR-21 attenuates excessive astrocyte activation and glial scar formation, thereby promoting axonal regeneration by regulating the epidermal growth factor receptor (EGFR) pathway. In addition, we observed that the expression of tissue inhibitor of metalloproteinase-3, a target gene of miR-21, was inhibited during this process. Taken together, these findings demonstrate that inhibition of miR-21 regulates the EGFR pathway, ameliorating excessive astrocyte activation and glial scar progression and promoting axonal regeneration and alleviating impairment in F-VEP function in a model of ONC. This study's results suggest that miR-21 may represent a therapeutic target for optic nerve injury.

The Role of MicroRNA in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a public health problem that causes high mortality and disability worldwide. Secondary brain damage from this type of injury may cause brain edema, blood-brain barrier destruction, and neurological dysfunction. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and play vital roles in maintaining and regulating physiological function. Notably, studies suggest that miRNA levels are altered in the cerebral cortex and hippocampus of rats and mice after TBI. These miRNAs exhibit promoting or inhibiting effects on the formation of secondary brain damage, such as promotion of neuron regeneration and apoptosis, alleviation of leakage across the blood-brain barrier (BBB), disruption of intracellular transport, and decreasing the inflammatory response. miRNA levels are also altered in the blood and cerebral spinal fluid (CSF) of humans with TBI. Some special miRNAs in blood were used in clinical trials for TBI diagnosis and prognosis prediction. Treatment with miRNA agomirs or antagomirs alleviated the lesion volume and improved neurological deficits post-injury. We review the current progress of miRNA studies in TBI patients and animal models and identify the prospects and difficulties involved in the clinical applications of miRNAs.

Intrasellar dermoid cyst mimicking pituitary apoplexy: A case report and review of the literature.

Intrasellar dermoid cysts are extremely unusual lesions, with only four cases reported to date, and have not been previously reported in association with sudden-onset symptoms. Here, we present the case of an intrasellar dermoid cyst with sudden-onset symptoms mimicking pituitary apoplexy in an elderly woman. A 69year-old woman presented with sudden onset of headache, dizziness, and decreased visual acuity. Magnetic resonance imaging of the sellar region showed an intrasellar lesion, which showed mixed hyper- and hypointense signal on T1-weighted and T2-weighted images and enhanced peripherally. Endocrine workup showed pituitary hormones within normal levels. According to these findings, the initial diagnosis of nonsecreting pituitary macroadenoma apoplexy was made. Intraoperatively, a large amount of whitish-yellow purulent material was found in the mass and the lesion was partially removed, owing to tight adhesion between remanent mass and surrounding neurovascular structures. Pathology showed a dermoid cyst with abundant neutrophil infiltrations.

Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation.

The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of ß-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt. At the same time, the repression of NSCs proliferation caused by Porf-2 overexpression was counteracted by small molecule activators of Rac1 or Wnt. By using a rat optic nerve crush model, we observed that Porf-2 knockdown enhanced the recovery of visual function. In particular, optic nerve injury in rats led to increased Wnt family member 3a (Wnt3a) protein expression, which we found responsible for enhancing Porf-2 knockdown-induced NSCs proliferation. These findings suggest that Porf-2 exerts its inhibitory effect on NSCs proliferation via Rac1-Wnt/ß-catenin pathway. Porf-2 may therefore represent and interesting target for optic nerve injury recovery and therapy.