Preoperative diffusion tensor imaging: Fiber-trajectory-distribution-based tractography to identify facial nerve in vestibular schwannoma.

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

Simultaneous hemorrhage of multiple cerebral cavernous malformations of the insular lobe and Meckel's cave: a case report and literature review.

We describe a case of sporadic cavernous malformation (CM) in a patient suffering from multiple hemorrhagic intracranial lesions, including one originating from the trigeminal nerve (TN). The patient presented with left side facial pain and disturbed right limb movement. The patient was pre-operatively diagnosed with multiple cerebral CMs. This diagnosis was confirmed by postoperative pathology.

Safe Region of Craniotomy to Access the Cerebellopontine Region by Retrosigmoid Approach: A Radiological and Anatomical Study.

Accurately positioning the sigmoid sinus (SS), transverse sinus (TS), and vertebral artery (VA) is significantly important during the retrosigmoid (RS) approach. This study aimed to use emissary vein and digastric point as landmarks in high-resolution computer topographic image to locate the SS, TS, and VA to help surgeons to avoid injuring these vascular structures during RS craniotomy. Computed topographic (CT) angiography images of 107 individuals were included, the measurement was performed on coronal, sagittal, and axis planes after the multiplanar reformation. Distance from the emissary vein and digastric point to the posterior boundary of the SS, inferior boundary of the TS were measured by CT angiography preoperatively and in the skull intraoperatively. The VA was also located by emissary vein and digastric point. No significant difference was identified between the distances measured in the CT and skull. Our findings provide anatomical information for locating the boundary of the SS, TS, and V3-VA based on the fixed bony landmarks. Verified by skull measurement, high-resolution CT scan is a cost-effective and reliable tool for identifying the location of the arteries and sinus, which could be widely used to guarantee the safety of RS approach craniectomy.

Automatic oculomotor nerve identification based on data-driven fiber clustering.

The oculomotor nerve (OCN) is the main motor nerve innervating eye muscles and can be involved in multiple flammatory, compressive, or pathologies. The diffusion magnetic resonance imaging (dMRI) tractography is now widely used to describe the trajectory of the OCN. However, the complex cranial structure leads to difficulties in fiber orientation distribution (FOD) modeling, fiber tracking, and region of interest (ROI) selection. Currently, the identification of OCN relies on expert manual operation, resulting in challenges, such as the carries high clinical, time-consuming, and labor costs. Thus, we propose a method that can automatically identify OCN from dMRI tractography. First, we choose the multi-shell multi-tissue constraint spherical deconvolution (MSMT-CSD) FOD estimation model and deterministic tractography to describe the 3D trajectory of the OCN. Then, we rely on the well-established computational pipeline and anatomical expertise to create a data-driven OCN tractography atlas from 40 HCP data. We identify six clusters belonging to the OCN from the atlas, including the structures of three kinds of positional relationships (pass between, pass through, and go around) with the red nuclei and two kinds of positional relationships with medial longitudinal fasciculus. Finally, we apply the proposed OCN atlas to identify the OCN automatically from 40 new HCP subjects and two patients with brainstem cavernous malformation. In terms of spatial overlap and visualization, experiment results show that the automatically and manually identified OCN fibers are consistent. Our proposed OCN atlas provides an effective tool for identifying OCN by avoiding the traditional selection strategy of ROIs.

Somatic MAP3K3 and PIK3CA mutations in sporadic cerebral and spinal cord cavernous malformations.

Cavernous malformations affecting the CNS occur in ∼0.16-0.4% of the general population. The majority (85%) of cavernous malformations are in a sporadic form, but the genetic background of sporadic cavernous malformations remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in two genes: MAP3K3 and PIK3CA by whole-exome sequencing. The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, odds ratio = 11.252, 95% confidence interval = 2.275-55.648). Enrichment of endothelial cell population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of endothelial cell models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic cavernous malformations were identified by single cell RNA sequencing and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic cavernous malformations and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic cavernous malformations.

Tractography of the stria terminalis in the human brain.

The aim of this study was to investigate the trajectory of the stria terminalis and develop a protocol for mapping the stria terminalis using multi-shell diffusion images based tractography. The stria terminalis was reconstructed by combining one region of interest at the amygdala with another region of interest at the bed nucleus of stria terminalis. In addition, one region of avoidance was placed on the fornix at the interventricular foramen and another was set at the anterior perforated substance. The fiber-tracking protocol was tested in a Human Connectome Project-842 template, 35 healthy subjects from Massachusetts General Hospital, and 20 healthy subjects from the Human Connectome Project using generalized q-sampling imaging based tractography. The stria terminalis was reconstructed in the Human Connectome Project-842 template, 35 Massachusetts General Hospital healthy subjects, and 20 Human Connectome Project healthy subjects with our protocol. The stria terminalis originated from the amygdala and traveled parallel to the fornix. Then, the stria terminalis followed a C-shaped trajectory around the inferior, posterior, and dorsal surfaces of the thalamus before projecting to the bed nucleus of stria terminalis between the thalamus and caudate nucleus. There were no significant differences in the quantitative anisotropy and fractional anisotropy values between the left and right stria terminalis. The stria terminalis was accurately visualized across subjects using multi-shell diffusion images through generalized q-sampling imaging based tractography. This method could be an important tool for the reconstruction and evaluation of the stria terminalis in various neurological disorders. One Sentence Summary The visualization of the stria terminalis through the multi-shell diffusion images using generalized q-sampling imaging based tractography.

Tractography of the ansa lenticularis in the human brain.

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.

The trajectory of the medial longitudinal fasciculus in the human brain: A diffusion imaging-based tractography study.

The aim of this study is to investigate the trajectory of medial longitudinal fasciculus (MLF) and explore its anatomical relationship with the oculomotor nerve using tractography technique. The MLF and oculomotor nerve were reconstructed at the same time with preset three region of interests (ROIs): one set at the area of rostral midbrain, one placed on the MLF area at the upper pons, and one placed at the cisternal part of the oculomotor nerve. This mapping protocol was tested in an HCP-1065 template, 35 health subjects from Massachusetts General Hospital (MGH), 20 healthy adults and 6 brainstem cavernous malformation (BCM) patients with generalized q-sampling imaging (GQI)-based tractography. Finally, the 200 µm brainstem template from Center for In Vivo Microscopy, Duke University (Duke CIVM), was used to validate the trajectory of reconstructed MLF. The MLF and oculomotor nerve were reconstructed in the HCP-1065 template, 35 MGH health subjects, 20 healthy adults and 6 BCM patients. The MLF was in conjunction with the ipsilateral mesencephalic part of the oculomotor nerve. The displacement of MLF was identified in all BCM patients. Decreased QA, RDI and FA were found in the MLF of lesion side, indicating axonal loss and/or edema of displaced MLF. The reconstructed MLF in Duke CIVM brainstem 200 µm template corresponded well with histological anatomy. The MLF and oculomotor nerve were visualized accurately with our protocol using GQI-based fiber tracking. This GQI-based tractography is an important tool in the reconstruction and evaluation of MLF.

Automated facial-vestibulocochlear nerve complex identification based on data-driven tractography clustering.

Small size and intricate anatomical environment are the main difficulties facing tractography of the facial-vestibulocochlear nerve complex (FVN), and lead to challenges in fiber orientation distribution (FOD) modeling, fiber tracking, region-of-interest selection, and fiber filtering. Experts need rich experience in anatomy and tractography, as well as substantial labor costs, to identify the FVN. Thus, we present a pipeline to identify the FVN automatically, in what we believe is the first study of the automated identification of the FVN. First, we created an FVN template. Forty high-resolution multishell data were used to perform data-driven fiber clustering based on the multishell multitissue constraint spherical deconvolution FOD model and deterministic tractography. We selected the brainstem and cerebellum (BS-CB) region as the seed region and removed the fibers that reach other brain regions. We then performed spectral fiber clustering twice. The first clustering was to create a BS-CB atlas and separate the fibers that pass through the cerebellopontine angle, and the other one was to extract the FVN. Second, we registered the subject-specific fibers in the space of the FVN template and assigned each fiber to the closest cluster to identify the FVN automatically by spectral embedding. We applied the proposed method to different acquirement sites, including two different healthy datasets and two tumor patient datasets. Experimental results showed that our automatic identification results have ideal colocalization with expert manual identification in terms of spatial overlap and visualization. Importantly, we successfully applied our method to tumor patient data. The FVNs identified by the proposed method were in agreement with intraoperative findings.

Comparison of surgical outcomes in cystic and solid vestibular schwannomas: a systematic review and meta-analysis.

Most studies reported that cystic vestibular schwannoma (CVS) surgery has a less favourable prognosis than solid vestibular schwannoma (SVS) surgery. However, some studies report that it is unclear whether surgical outcomes for these conditions exhibit significant differences. The aim of this meta-analysis was to pool the current literature and describe and analyse any differences in the clinical symptoms and surgical outcomes among CVS and SVS. PubMed, Embase, and Cochrane databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines through April 22, 2020. Outcomes were analysed using a meta-analysis of the proportions. The results of the search yielded 17 studies that met the criteria for inclusion and analysis, involving 3074 participants (including 821 patients with CVSs and 2253 patients with SVSs). No significant differences in the extent of tumour resection (gross-total resection versus non-gross-total resection; RR, 0.93; 95% CI, 0.86-1.01; p = 0.096) and most other outcomes were noted between CVS and SVS cohorts. However, facial nerve function (House-Brackmann Grade I or II versus III or more) of CVS patients was worse (RR, 0.86; 95% CI, 0.78-0.93; p < 0.001) compared with SVS patients with more than 1 year of follow-up after surgery. The criteria of cystic acoustic neuroma needs to be further unified, and prospective cohort studies with larger sample sizes should be performed for further verification of these results in the future.

Trigeminal schwannoma: a single-center experience with 43 cases and review of literature.

OBJECTIVE: Trigeminal schwannomas (TS) are rare, when compared to vestibular schwannomas. The present study aims to analyze the clinical characteristics and surgical strategies of TS via the retrospective analysis of the clinical data of 43 patients. METHODS: The clinical information of 43 patients diagnosed with TS, who were surgically treated from January 2008 to January 2018, was retrospectively analyzed. Then, the selection of approaches and surgical strategies were discussed. RESULTS: During the last 10 years, 43 patients with TS received surgical treatment at Xuan Wu Hospital of Capital Medical University. Facial numbness and hypoesthesia were the most common symptoms, which developed in 29 cases (67.4%). Typical trigeminal neuralgia was complained by four patients (9.3%), while trigeminal motor impairment developed in nine cases (20.9%). The tumor was totally removed in 39 patients (90.7%), near-totally removed in three patients (7.0%), and partially removed in one patient (2.3%) due to intraoperative internal carotid artery (ICA) injury. The abducens was intraoperatively damaged in two patients (4.7%). After the operation, all four patients with trigeminal neuralgia achieved total recovery, but the facial numbness still continued in 24 patients (82.8%). At a median of 45.3 ± 25.5 (6-84) months of follow up, a tumor recurred in only one patient, and this patient received a second operation. CONCLUSION: It can be concluded that total removal via the proper approach can be the best treatment for TS with a low complication rate. However, preoperative symptoms, such as facial numbness and trigeminal motor impairment that seldom improved though normal fibers, were carefully recognized and preserved during the operation.

Rapid formation and rupture of an infectious basilar artery aneurysm from meningitis following suprasellar region meningioma removal: a case report.

BACKGROUND: Infectious basilar artery (BA) aneurysm has been occasionally reported to be generated from meningitis following transcranial operation. However, infectious BA aneurysm formed by intracranial infection after endoscopic endonasal operation has never been reported. CASE PRESENTATION: A 53-year-old man who was diagnosed with suprasellar region meningioma received tumor removal via endoscopic endonasal approach. After operation he developed cerebrospinal fluid (CSF) leak and intracranial infection. The patient ultimately recovered from infection after anti-infective therapy, but a large fusiform BA aneurysm was still formed and ruptured in a short time. Interventional and surgical measures were impossible due to the complicated shape and location of aneurysm and state of his endangerment, therefore, conservative anti-infective therapy was adopted as the only feasible method. Unfortunately, the aneurysm did not disappear and the patient finally died from repeating subarachnoid hemorrhage (SAH). CONCLUSION: Though extremely rare, it was emphasized that infectious aneurysm can be formed at any stage after transnasal surgery, even when the meningitis is cured. Because of the treatment difficulty and poor prognosis, it was recommended that thorough examination should be timely performed for suspicious patient to make correct diagnosis and avoid fatal SAH.

Trigeminal neuralgia caused by a dilated superior cerebellar artery and a draining vein of cerebellar arteriovenous malformations: a case report and review of the literature.

Trigeminal neuralgia (TN) secondary to arterivenous malformations (AVMs) is relatively rare. We here report on a case of TN caused by cerebellar AVMs that was successfully treated by total AVMs resection in conjunction with microvasecular decompression (MVD) in one stage. In addition, we perform a review of the literature about the treatment of TN caused by cerebellar AVMs.

Usefulness of intraoperative electromyographic monitoring of oculomotor and abducens nerves during skull base surgery.

BACKGROUND: Intraoperative neurophysiologic monitoring of the extraocular cranial nerve (EOCN) is not commonly performed because of technical difficulty and risk, reliability of the result and predictability of the postoperative function of the EOCN. METHODS: We performed oculomotor nerve (CN III) and abducens nerve (CN VI) intraoperative monitoring in patients with skull base surgery by recording the spontaneous muscle activity (SMA) and compound muscle action potential (CMAP). Two types of needle electrodes of different length were percutaneously inserted into the extraocular muscles with the free-hand technique. We studied the relationships between the SMA and CMAP and postoperative function of CN III and CN VI. RESULTS: A total of 23 patients were included. Nineteen oculomotor nerves and 22 abducens nerves were monitored during surgery, respectively. Neurotonic discharge had a positive predictive value of less than 50% and negative predictive value of more than 80% for postoperative CN III and CN VI dysfunction. The latency of patients with postoperative CN III dysfunction was 2.79 ± 0.13 ms, longer than that with intact CN III function (1.73 ± 0.11 ms). One patient had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than that of intact CN VI function (2.11 ± 0.38 ms). There was no statistically significant difference between patients with paresis and with intact function. CONCLUSIONS: The method of intraoperative monitoring of EOCNs described here is safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems to have limited value in predicting the postoperative function of CN III and CN VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably relevant to postoperative CN III and CN VI dysfunction. However, a definite quantitative relationship has not been found between the amplitude and stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.

Posterior interhemispheric transtentorial approach for resection of a meningioma at the posteromedial tentorial incisura.

The posterior interhemispheric approach is a versatile approach to access lesions of the pineal region, posterior incisural space, posterior region of third ventricle, and adjacent structures. We demonstrate the case of a 26-year-old woman with symptoms of increased intracranial pressure and hydrocephalus caused by a meningioma at the posteromedial tentorial incisura. Gross-total removal of the tumor was successfully achieved via a posterior interhemispheric transtentorial approach. The patient reported an immediate and significant symptomatic improvement after surgery. The detailed operative technique and surgical nuances, including the surgical corridor, tentorium incision, tumor dissection and removal are illustrated in this video atlas. The video can be found here: https://youtu.be/nSNyjQKl7aE .

Identification of cranial nerves around trigeminal schwannomas using diffusion tensor tractography: a technical note and report of 3 cases.

BACKGROUND: There are no large series studies identifying the locations of cranial nerves (CNs) around trigeminal schwannomas (TSs); however, surgically induced cranial neuropathies are commonly observed after surgeries to remove TSs. In this study, we preoperatively identified the location of CNs near TSs using diffusion tensor tractography (DTT). METHODS: An observational study of the DTT results and intraoperative findings was performed. We preoperatively completed tractography from images of patients with TSs who received surgical therapy. The result was later validated during tumorectomy. RESULTS: A total of three consecutive patients were involved in this study. The locations of CNs V-VIII in relation to the tumor was clearly revealed in all cases, except for CN VI in case 3.The predicted fiber tracts were in agreement with intraoperative observations. CONCLUSIONS: In this study, preoperative DTT accurately predicted the location of the majority of the nerves of interest. This technique can be applied by surgeons to preoperatively visualize nerve arrangements.

Identification of cranial nerves near large vestibular schwannomas using superselective diffusion tensor tractography: experience with 23 cases.

BACKGROUND: The preservation of the facial nerve (FN) and acoustic function in large vestibular schwannoma (VS) surgery is challenging because of nerve course uncertainties and morphological deviations. Preoperative diffusion tensor tractography (DTT) has been proposed to predict the FN location. This study was conducted to evaluate the effectiveness of this technique for identifying the FN, cochlear nerve (CN) and trigeminal nerve (TN) in large VSs. METHODS: The study included 23 consecutive patients with VS of Hannover classification T3b to T4b from November 2013 through May 2014. Diffusion tensor images and anatomical images were acquired. The DTT images of the cranial nerves were extracted before surgery for each patient to determine the relationships of these nerves with the tumor. The results were then validated during the tumorectomy. RESULTS: In 21 (91.30%) patients, the location of the FN on the DTT images agreed with the intraoperative findings, including in 2 patients in whom the FN passed through the interface between the parenchyma and the cystic changes and in 3 patients with a membranoid FN. The CN or fibers of unclear function were observed on DTT images in four patients with functional hearing. One penetrating fiber of unknown function was effectively constructed. The TN was accurately detected on the DTT images for all patients. CONCLUSIONS: DTT effectively revealed the location of the FN, including cases in which the FN was membranoid or passed through the interface between an area exhibiting cystic changes and the tumor nodule. Fibers aside from the FN and the TN were revealed by DTT in patients who retained functional hearing. Penetrating fibers were also found using DTT. This technique can be useful during VS resection.

[Descending hypoglossal branch-facial nerve anastomosis in treating unilateral facial palsy after acoustic neuroma resection].

OBJECTIVE: To evaluate the efficiency of the descending hypoglossal branch-facial nerve anastomosis for the severe facial palsy after acoustic neuroma resection. METHODS: The clinical data of 14 patients (6 males, 8 females, average age 45. 6 years old) underwent descending hypoglossal branch-facial nerve anastomosis for treatment of unilateral facial palsy was analyzed retrospectively. All patients previously had undergone resection of a large acoustic neuroma. House-Brackmann (H-B) grading system was used to evaluate the pre-, post-operative and follow up facial nerve function status. 12 cases (85.7%) had long follow up, with an average follow-up period of 24. 6 months. RESULTS: 6 patients had good outcome (H-B 2 - 3 grade); 5 patients had fair outcome (H-B 3 - 4 grade) and 1 patient had poor outcome (H-B 5 grade) Only 1 patient suffered hemitongue myoparalysis owing to the operation. CONCLUSION: Descending hypoglossal branch-facial nerve anastomosis is effective for facial reanimation, and it has little impact on the function of chewing, swallowing and pronunciation of the patients compared with the traditional hypoglossal-facial nerve anastomosis.

Investigating the neuroprotective potential of rAAV2-PCBP1-EGFP gene therapy against a 6-OHDA-induced model of Parkinson's disease.

OBJECTIVES: Previous studies have suggested a potential link between poly(rC)-binding protein 1 (PCBP1) and neurodegenerative diseases, including Parkinson's disease (PD). However, the precise role of PCBP1 in the pathogenesis of PD remains unclear. Therefore, the main objective of this study was to investigate the neuroprotective effects of PCBP1 in a PD model. METHODS: To evaluate the neuroprotective potential of PCBP1, we conducted cell count assays and observed the expression of heat shock protein 70 (HSP70) in SH-SY5Y cells exposed to 6-OHDA-induced neurotoxicity. Additionally, we utilized recombinant adeno-associated virus (rAAV2) vectors encoding PCBP1 or EGFP, which were injected into the rat striatum. After 2 weeks of vector or saline injection, 6-OHDA was administered to the rat striatum. Behavioral assessments using the open field test (OFT) were performed weekly for 7 weeks. At the seventh week after 6-OHDA injection, immunohistochemistry and protein expression analyses were conducted in the three groups. RESULTS: The results indicated that PCBP1 treatment significantly reduced the proliferation of 6-OHDA-induced SH-SY5Y cells. Additionally, in surviving cells, overexpression of PCBP1 enhanced the expression of HSP70. Similarly, rAAV2 vectors effectively delivered PCBP1 into the brain, resulting in sustained expression of rAAV2-PCBP1-EGFP. In the OFT, PCBP1 exhibited significant improvements in behavioral abnormalities and reduced anxiety in the PD model rats (p < .01). Moreover, PCBP1 effectively prevented the decrease of tyrosine hydroxylase and HSP70 expression in the lesioned side induced by 6-OHDA (p < .01). Consistent with expectations, PCBP1 efficiently protected against cell death caused by 6-OHDA (p < .01). CONCLUSIONS: In conclusion, our findings provide compelling evidence for the beneficial effects of PCBP1 in the PD model, suggesting that PCBP1 could be a potential therapeutic target for PD.

Poly(rC)-binding protein 1 alleviates neurotoxicity in 6-OHDA-induced SH-SY5Y cells and modulates glial cells in neuroinflammation.

BACKGROUND: Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons and neuroinflammation. Previous research has identified the involvement of Poly (rC)-binding protein 1 (PCBP1) in certain degenerative diseases; however, its specific mechanisms in PD remain incompletely understood. METHODS: In this study, 6-OHDA-induced neurotoxicity in the cell lines SH-SY5Y, BV-2 and HA, was used to evaluate the protective effects of PCBP1. We assessed alterations in BDNF levels in SY5Y cells, changes in GDNF expression in glial cells, as well as variations in HSP70 and NF-κB activation. Additionally, glial cells were used as the in vitro model for neuroinflammation mechanisms. RESULTS: The results indicate that the overexpression of PCBP1 significantly enhances cell growth compared to the control plasmid pEGFP/N1 group. Overexpression of PCBP1 leads to a substantial reduction in early apoptosis rates in SH-SY5Y, HA, and BV-2 cells, with statistically significant differences (p < 0.05). Furthermore, the overexpression of PCBP1 in cells results in a marked increase in the expression of HSP70, GDNF, and BDNF, while reducing NF-κB expression. Additionally, in SH-SY5Y, HA, and BV-2 cells overexpressing PCBP1, there is a decrease in the inflammatory factor IL-6 compared to the control plasmid pEGFP/N1 group, while BV-2 cells exhibit a significant increase in the anti-inflammatory factor IL-10. CONCLUSION: Our findings suggest that PCBP1 plays a substantial role in promoting cell growth and modulating the balance of neuroprotective and inflammatory factors. These results offer valuable insights into the potential therapeutic utility of PCBP1 in mitigating neuroinflammation and enhancing neuronal survival in PD.