Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.

Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Objective:To investigate the predictive value of fluid-attenuated inversion recovery (FLAIR) signal strength ratio (SIR) in onset time≤4.5 h in patients with acute ischemic stroke.Methods:A retrospective analysis was performed; 180 acute ischemic stroke patients admitted to Department of Neurology, Nanjing Hospital Affiliated to Nanjing Medical University from January 2020 to June 2023 were chosen. Hypoperfusion intensity ratio (HIR) was used to evaluate the collateral circulation (poor collateral circulation: HIR≤0.4; good collateral circulation: HIR>0.4); clinical data and imaging indexes between poor collateral circulation and good collateral circulation groups were compared. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for onset time≤4.5 h in patients with acute ischemic stroke. Correlation between SIR and onset time was analyzed in patients with acute ischemic stroke. Role of HIR as agency between SIR and onset time was explored. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of SIR and diffusion weighted imaging (DWI)-FLAIR mismatch in onset time≤4.5 h in acute ischemic stroke patients.Results:Of the 180 patients, 100 were into the good collateral circulation group and 80 were into the poor collateral circulation group; compared with the good collateral circulation group, the poor collateral circulation group had significantly higher percentage of patients with hyperlipidemia, larger DWI infarction volume before treatment, larger perfusion weighted imaging (PWI)-DWI mismatch volume and higher SIR ( P<0.05). In these 180 patients, 76 had onset time≤4.5 h and 104 had onset time>4.5 h. Univariate Logistic regression analysis showed that hyperlipidemia, DWI infarct volume before treatment, DWI-FLAIR mismatch, HIR and SIR were influencing factors for onset time≤4.5 h in acute ischemic stroke patients ( P<0.05). Multivariate Logistic regression analysis showed that hyperlipidemia ( OR=6.654, 95% CI: 5.751-8.824, P<0.001), HIR ( OR=0.724, 95% CI: 0.521-1.321, P=0.041) and SIR ( OR=739.881, 95% CI: 383.296-14 258.065, P<0.001) were independent influencing factors for onset time≤4.5 h in acute ischemic stroke patients. Pearson correlation analysis showed that SIR was positively correlated to onset time in patients with acute ischemic stroke ( r=0.420, P<0.05), and SIR was positively correlated to onset time in patients from poor collateral circulation group ( r=0.781, P<0.05). ROC curve showed that AUC of SIR in predicting onset time≤4.5 h was 0.917 (95% CI: 0.814-1.000, P<0.001) and that of DWI-FLAIR mismatch in predicting onset time≤4.5 h was 0.530 (95% CI: 0.509-0.757, P=0.075) in poor collateral circulation group, enjoying significant difference in predictive efficacy. Conclusion:Acute ischemic stroke patients with low HIR and SIR have higher odds of onset time≤4.5 h; SIR can more accurately predict the onset time in these patients with poor collateral circulation.

Objective:To analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Objective:To investigate the efficacy of microscopic decompression in degenerative lumbar spinal stenosis (DLSS) under single percutaneous tubular retractor system.Methods:A retrospective analysis was performed; 117 DLSS patients with imaging manifestations as non-segmental lumbar instability, admitted to Department of Neurosurgery, 900 th Hospital of PLA Joint Logistics Team from October 2018 to April 2023 were enrolled consecutively. These patients failed in strict conservative treatment and then changed to posterior lumbar spinal canal and nerve root decompression by microscopy and percutaneous tubular retractor system. These patients were followed up for 6-50 months. Pain visual analogue score (VAS) and lumbar Oswestry dysfunction index (ODI) were recorded and results of X-rays, CT and MRI of lumbar spines were analyzed 1 d before and 1 week after decompression and at the last follow-up. Modified MacNab criteria were used to evaluate the efficacy at the last follow-up. Results:Among the 117 patients, unilateral laminectomy for unilateral decompression was performed in 56 patients (47.9%) and unilateral laminotomy for bilateral decompression in 61 (52.1%). Single segment decompression was performed in 109 patients (93.2%) and double segment decompression in 8 (6.8%). Dural sac rupture occurred in 4 patients (3.5%), and immediate occlusion was given; no cerebrospinal fluid leakage was noted after decompression. All patients did not experience obvious nerve damage during decompression or intervertebral infection/lumbar instability after decompression. After 18 (13, 24) months of follow-up, VAS scores of the patients at the last follow-up decreased from (5.96±0.85) 1 d before decompression and (1.75±0.61) 1 week after decompression to (1.01±0.59), and lumbar ODI decreased from (63.22±8.33)% 1 d before decompression and (17.66±5.20)% 1 week after decompression to (10.64±3.44)%, with significant differences ( P<0.05). At the last follow-up, modified MacNab criteria indicated 46 patients (39.3%) as excellent, 66 (56.4%) as good, 3 (2.6%) as fair, and 2 (1.7%) as poor, with an excellent/good therapeutic rate of 95.7%. Conclusion:For surgical treatment of DLSS patients without evidenced preoperative spinal instability, personalized unilateral or bilateral spinal canal decompression under microscope by combiningsingle percutaneous tubular retractor system can effectively reduce surgical trauma and achieve satisfactory surgical results.

Objective:To compare the morphological differences of psoas major muscles between patients with lumbar disc herniation (LDH) of lower limb pain and lumbocrural pain based on CT imaging data.Methods:Sixty patients with LDH admitted to Department of Neurosurgery, 900 th Hospital of PLA Joint Logistic Team from January 2012 to February 2023 were included. According to clinical symptoms, they were divided into lower limb pain group and lumbocrural pain group ( n=30). 3D CT images of the psoas major muscles in the 2 groups were reconstructed; the longest transverse axis perpendicular to the longitudinal axis of the psoas major muscle was chosen as the cross-sectional area, and the maximum psoas major muscle cross-sectional area was calculated; maximum psoas major muscle cross-sectional area index (PI max) was defined as ratio of maximum psoas major muscle cross-sectional area and L 5 vertebral cross-sectional area. PI max difference between lower limb pain group and lumbocrural pain group was compared; PI max difference among patients with different pain degrees (visual analog scale [VAS] scores) or pain courses was further compared in both lower limb pain group and lumbocrural pain group. Pearson correlation was used to analyze the correlations of PI max with pain degree and pain course in the 2 groups. Results:PI max in lower limb pain group was significantly larger than that in lumbocrural pain group (0.62±0.05 vs. 0.54±0.04, t=7.320, P<0.001). PI max in patients with severe pain from both lower limb pain group and lumbocrural pain group was significantly smaller than that in patients with moderate pain (0.61±0.05 vs. 0.65±0.04, t=2.422, P=0.022; 0.53±0.03 vs. 0.58±0.04, t=3.502, P=0.002). PI max in patients with short pain course from both lower limb pain group and lumbocrural pain group was significantly larger than that in patients with long pain course (0.64±0.05 vs. 0.59±0.04, t=2.570, P=0.016; 0.57±0.04 vs. 0.53±0.03, t=2.941, P=0.007). Pearson correlation showed that PI max was negatively correlated with pain degree and pain course in LDH patients from both groups ( P<0.05). Conclusion:Atrophy of psoas major muscles in LDH patients is aggravated with increased pain degree and pain course.

The hippocampus and its circuits play crucial roles in human learning, memory, and emotional regulation. Whether it is vascular cognitive impairment (VCI) or Alzheimer's disease (AD), damage to the hippocampus is a prominent pathological feature. This review summarizes the recent advance in multimodal magnetic resonance imaging in anatomy, blood supply, structure and function of the hippocampus and the circuits related to VCI and AD in recent years, aiming to provide help in early recognizing and differentially diagnosing VCI and AD.