Neurological Recovery Research Articles

Clinical Assessment and Management of Acute Spinal Cord Injury.

The information contained in this article is suitable for clinicians practicing in the United States desiring a general overview of the assessment and management of spinal cord injury (SCI), focusing on initial care, assessment, acute management, complications, prognostication, and future research directions. SCI presents significant challenges, affecting patients physically, emotionally, and financially, with variable recovery outcomes ranging from full functionality to lifelong dependence on caregivers. Initial care aims to minimize secondary injury through thorough neurological evaluations and imaging studies to assess the severity of the injury. Acute management prioritizes stabilizing respiratory and cardiovascular functions and maintaining proper spinal cord perfusion. Patients with unstable or progressive neurological decline benefit from timely surgical intervention to optimize neurological recovery. Subacute management focuses on addressing common complications affecting the respiratory, gastrointestinal, and genitourinary systems, emphasizing a holistic, multidisciplinary approach. Prognostication is currently based on neurological assessments and imaging findings, but emerging biomarkers offer the potential to refine outcome predictions further. Additionally, novel therapeutic interventions, such as hypothermia therapy and neuroprotective medications are being explored to mitigate secondary damage and enhance recovery. This paper serves as a high-yield refresher for clinicians for the assessment and management of acute spinal cord injury during index admission.

Acute disseminated encephalomyelitis in a five-year-old girl: a case report

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating central nervous system disorder with a predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrence has been described and defined as multiphasic disseminated encephalomyelitis (MDEM). ADEM often occurs after infection or immunization and is clinically defined as acute polyfocal neurological deficits, including encephalopathy. Many times, ADEM is a diagnosis of exclusion, and early diagnosis and treatment are the keys to favorable outcomes. Magnetic resonance imaging (MRI) typically demonstrates reversible, large, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal mild pleocytosis and elevated protein but is generally negative for intrathecal oligoclonal bands. We report a case of five years six-month- old girl who presented with fever, vomiting, headache, and cough for seven days. She had one episode of involuntary passage of urine. The child was lethargic at presentation and was unable to stand or walk. Clinical features and investigations, including MRI brain and spine, were suggestive of ADEM. She was started on Inj. Methylprednisolone followed by oral prednisolone in tapering dose for four weeks. Clinical improvement was seen in the form of improvement in activity and power in limbs. The child improved with normal neurological function on day three of inj methylprednisolone. On follow-up for six months, the child did not have any relapse and had complete neurological and radiological recovery.

Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage: an analysis of clinical samples.

We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. We designed two clinical cohort studies to explore the gut dysbiosis after ICH and their relationship with neurological function prognosis. First, fecal samples from patients with ICH at three time points: T1 (within 24 h of admission), T2 (3 days after surgery), and T3 (7 days after surgery), and healthy volunteers were subjected to 16S rRNA sequencing using Illumina high-throughput sequencing technology. When differential gut microbiota was identified, the correlation between clinical indicators and microbiotas was analyzed. Subsequently, the patients with ICH were categorized into GOOD and POOR groups based on their Glasgow Outcome Scale Extended (GOS-E) score, and the disparities in gut microbiota between the two groups were assessed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The composition and diversity of the gut microbiota in patients with ICH were different from those in the control group and changed dynamically with the extension of the course of cerebral hemorrhage. The abundances of Enterococcaceae, Clostridiales incertae sedis XI, and Peptoniphilaceae were significantly increased in patients with ICH, whereas Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, and Veillonellaceae were significantly reduced. The relative abundance of Enterococcus gradually increased with the extension of the duration of ICH after surgery, and the abundance of Bacteroides gradually decreased. The abundance of Enterococcus before surgery was found to be negatively associated with patient neurological function prognosis. The original ICH score and Lachnospiraceae status were independent risk factors for predicting the prognosis of neurological function in patients with ICH (P < 0.05). Changes in the gut microbiota diversity in patients with ICH were related to prognosis. Lachnospiraceae may have a protective effect on prognosis.IMPORTANCEAcute central nervous system injuries like hemorrhagic stroke are major global health issues. While surgical hematoma removal can alleviate brain damage, severe cases still have a high 1-month mortality rate of up to 40%. Gut microbiota significantly impacts health, and treatments like fecal microbiota transplantation (FMT) and probiotics can improve brain damage by correcting gut microbiota imbalances caused by ischemic stroke. However, few clinical studies have explored this relationship in hemorrhagic stroke. This study investigated the impact of cerebral hemorrhage on the composition of gut microbiota, and we found that Lachnospiraceae were the independent risk factors for poor prognosis in intracerebral hemorrhage (ICH). The findings offer potential insights for the application of FMT in patients with ICH, and it may improve the prognosis of patients.

Development and Testing of the Spinal Cord Injury Bladder and Bowel Control Questionnaire (SCI-BBC-Q).

Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient-reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI-BBC-Q) was developed. The SCI-BBC-Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI-BBC-Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. The final 6-item SCI-BBC-Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI-BBC-Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI-BBC-Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. The SCI-BBC-Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery.

Clinical Spectrum and EEG Findings in Patients with Suspected Non-Convulsive Status Epilepticus

This study looked at the clinical spectrum as well as EEG results to help diagnose and treat patients with probable non-convulsive status epilepticus (NCSE). Patients were classified into two groups based on the degree of NCSE: mild to moderate and severe and their medical records revealed evidence of epilepsy in the form of rhythmic delta activity and localized slowing or widespread spike-and-wave (WSW) discharges in EEG. Severe NCSE was associated with increased antiepileptic drug use (90 vs 80%), longer treatment duration (10 vs 7days), and higher critical care unit admissions (40vs25%) (p&lt;0.05). EEG data showed a significant increase in the frequency of generalized spike-and-wave discharges (45 vs 30%) and localized slowing (32vs20%) (p&lt;0.05). Furthermore, these patients' neurological recovery was worse and they remained in the hospital longer. Finally, the severity of the NCSE and poor clinical outcomes were substantially linked to specific EEG patterns, especially localized slowing and WSW discharges.

K-Line Tilt May Influence the Short-Term Surgical Outcomes After Laminoplasty in Patients With Degenerative Cervical Myelopathy.

A retrospective study. To explore the relationship between K-line tilt and short-term surgical outcomes following laminoplasty in patients with multilevel degenerative cervical myelopathy (DCM), and to evaluate the potential of K-line tilt as a reliable preoperative predictor. A retrospective analysis was performed for 125 consecutive patients who underwent laminoplasty for multilevel DCM. The radiographic parameters utilized in this study encompassed T1 slope (T1S), C2-C7 lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope minus C2-C7 lordosis (T1S-CL), C2-C7 range of motion (ROM), and K-line tilt. The neurological recovery was evaluated using the Japanese Orthopaedic Association (JOA) score. Pearson correlation coefficients were calculated to assess the relationship between K-line tilt and other classical cervical parameters. Logistic regression analysis was employed to examine the association between K-line tilt and surgical outcomes. Of the 125 patients, 89 were men. The mean age of the patients was 61.74 ± 11.31 years. The results indicated a correlation between the K-line tilt and the cSVA (r = 0.628, P < 0.001), T1S (r = 0.259, P = 0.004), and T1S-CL (r = 0.307, P < 0.001). The K-line tilt showed an association with the failure of the JOA recovery rate (RR) to reach the minimal clinically important difference (MCID) and the occurrence of postoperative kyphotic deformity. We identified cutoff values for the K-line tilt which predict the failure of the JOA RR to reach the MCID and postoperative kyphotic deformity as 10.13° and 9.93°, respectively. The K-line tilt is an independent preoperative risk factor associated with both the failure of the JOA RR to reach the MCID and the occurrence of postoperative kyphotic deformity in patients with multilevel DCM after laminoplasty.

Temporal Pattern of Individual Neurological Function Recovery in Guillain-Barré Syndrome.

Background: There is paucity of studies on the temporal pattern of recovery of facial, bulbar, sensory, motor, and autonomic dysfunction in Guillain-Barré syndrome (GBS), although many studies have reported short- and long-term functional outcomes. We report the temporal pattern of recovery of various neurological functions in GBS, and compare the pattern of recovery between acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Methods: Forty-two patients with GBS were prospectively included, and their clinical details, including peak disability on a 0-6 scale, were noted. The day of complete recovery in motor, sensory, facial, bulbar, and autonomic functions during 3 months of follow-up was recorded. Results: Complete recovery of autonomic function occurred in all (median, 12 days), bulbar weakness in 91.3% (median, 15 days), facial weakness in 86.2% (median, 19 days), and sensory functions in 82.1% (median, 20 days). Only 9.5% of patients achieved normal motor function within 3 months. The days of complete recovery of bulbar, facial, autonomic, and motor deficits were comparable between AIDP and AMAN. Demyelinating GBS had an earlier recovery of bulbar and sensory functions. Conclusions: The neurological recovery in GBS occurs first in the autonomic, followed by the bulbar, facial, sensory, and motor functions. The demyelinating type had an earlier recovery of bulbar and sensory functions.

Impact of socioeconomic status on cardiac arrest outcomes during COVID-19 pandemic

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has affected healthcare services, potentially leading to inequitable outcomes based on patients’ socioeconomic status (SES). This study aimed to evaluate the impact of COVID-19 on out-of-hospital cardiac arrest (OHCA) outcomes by examining disparities across SES levels. MethodsThe study analyzed non-traumatic OHCA cases registered in the Korean Out-of-Hospital Cardiac Arrest Registry from 2010 to 2021, encompassing 238,668 patients aged 18 years and older. SES was assessed at both the individual (Medicaid vs non-Medicaid) and area levels using a deprivation index. Outcomes included any return of spontaneous circulation, survival to admission, survival to discharge, and favorable neurological recovery. Logistic regression and generalized additive models (GAMs) were used for analysis. ResultsOHCA outcomes—including survival to admission, survival to discharge, and favorable neurological recovery—improved over the years, peaking in 2019 before subsequently declining. Logistic regression showed that the lowest SES area was associated with lower rates of ROSC (adjusted odds rations [aOR] 0.82, 95 % confidence interval [CI] 0.75–0.88) and survival to admission (aOR 0.56, 95%CI 0.49–0.64) and discharge (aOR 0.78, 95%CI 0.61–0.98) during the pandemic. GAM analysis revealed that lower SES groups (deprivation index levels 4 and 5) experienced higher-than-expected survival to admission and discharge rates, as well as favorable neurological recovery. Although outcomes in the deprivation index level 1 group (5.5 % in 2021) remained superior, indicating poor outcomes for the lowest SES area group (3.43 % in 2021), the disparity decreased following the pandemic. ConclusionLower levels of SES are a significant risk factor for unfavorable neurological recovery in OHCA, independent of the COVID-19 pandemic. However, SES-related disparities in the outcomes decreased post-pandemic. Despite the overall negative impact of COVID-19, certain lower SES groups showed improved survival rates, likely due to differences in the EMS response and healthcare burden across regions.

Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury

Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

Anterior decompression and posterior total laminectomy with fusion for ossification of the cervical posterior longitudinal ligament.

Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre. Included in this retrospective cohort study were 48 patients (12 females; mean age 55.79 years (SD 8.94)) who were diagnosed with cervical OPLL, received treatment in our centre, and were followed up for 10.22 to 15.25 years. Of them, 24 patients (six females; mean age 52.88 years (SD 8.79)) received ADF, and the other 24 patients (five females; mean age 56.25 years (SD 9.44)) received PLF. Clinical data including age, sex, and the OPLL canal-occupying ratio were analyzed and compared. The primary outcome was Japanese Orthopaedic Association (JOA) score, and the secondary outcome was visual analogue scale neck pain. Compared with the baseline, neurological function improved significantly after surgery in all patients of both groups (p < 0.001). The JOA recovery rate in the ADF group was significantly higher than that in the PLF group (p < 0.001). There was no significant difference in postoperative cervical pain between the two groups (p = 0.387). The operating time was longer and intraoperative blood loss was greater in the PLF group than the ADF group. More complications were observed in the ADF group than in the PLF group, although the difference was not statistically significant. Long-term neurological function improved significantly after surgery in both groups, with the improvement more pronounced in the ADF group. There was no significant difference in postoperative neck pain between the two groups. The operating time was shorter and intraoperative blood loss was lower in the ADF group; however, the incidence of perioperative complications was higher.

Quercetin alleviates microglial-induced inflammation after traumatic brain injury via the PGC-1α/Nrf2 pathway dependent on HDAC3 inhibition

Inflammation and neuronal apoptosis play a key role in traumatic brain injury (TBI). Quercetin (Que) has been shown to exhibit a neuroprotective effect after TBI, but the underlying molecular mechanism remains unclear. In this study, We established a weight-drop mouse model to illustrate the effects of Que on microglial-induced inflammation in TBI. Mice were divided into four groups: the Sham group, TBI group, TBI+vehicle group, and TBI+Que group. The TBI+Que group was treated with Que 30 min after TBI. Brain water content, neurological score, and neuronal apoptosis were measured. Western blotting, TUNEL staining, Nissl staining, quantitative polymerase chain reaction, and immunofluorescence staining were performed to assess the activation of the PGC-1α/Nrf2 pathway and nuclear translocation of HDAC3 with Que treatment. The results showed that Que administration alleviated TBI-induced neurobehavioral deficits, encephaledema, and neuron apoptosis. Que also restrained TBI-induced microglial activity and the subsequent expression of the inflammatory factor in the contusion cortex. Moreover, Que treatment activated the PGC-1α/Nrf2 pathway, attributable to the inhibition of HDAC3 translocation to the nucleus. Overall, these results reveal the role of Que in protecting against TBI-induced neuroinflammation and promoting neurological functional recovery, which is achieved through the negative regulation of HDAC3.

Transcranial Corticospinal Motor-Evoked Potentials in Cases of Ventral and Ventrolateral Intradural Extramedullary Cervical Spinal Cord Tumors.

Background and Objectives: We studied the clinical significance of an amplitude decrement and disappearance alarm criteria in transcranial motor-evoked potential (MEP) monitoring during surgeries on extramedullary tumors at the cervical spine with reference to postoperative morbidity. Material and Methods: We diagnosed and surgically treated fourteen patients with intradural extramedullary ventral or ventrolateral lesions to the cervical spinal cord in the Clinic of Neurosurgery at the University Hospital St Ivan Rilski from January 2018 to July 2022. Eight cases were diagnosed with schwannoma, and the remaining six had meningiomas. The follow-up period for neurological assessment was six months. Results: A decrease in the intraoperative transcranial MEPs of 50% or more compared to baseline in two cases (14.3%) resulted in an immediate postoperative motor deficit. One patient demonstrated full neurological recovery within six months, while the other exhibited only partial improvement. In six cases (42.9%) with preoperative motor deficits, tumor resection and decompression of the cervical spinal cord led directly to an increment of the transcranial MEPs by more than 20%. Postoperatively and at the 6-month follow-up, these patients showed recovery from the preoperative deficits. In the remaining cases, MEPs were stable during surgery with no clinical deterioration of the motor function. Conclusions: The decremented MEP criteria corresponded to postoperative motor deficit, whereas the improvement of the same parameters after decompression implied future recovery of preoperative motor deficits. The combination of different MEP criteria is likely to be helpful when tailored to a specific case of ventral or ventrolateral extramedullary lesions in the cervical spine.

AN OVERLAP OF GUILLAIN-BARRÉ SYNDROME, MILLER-FISHER SYNDROME, AND BICKERSTAFF BRAINSTEM ENCEPHALITIS PRESENTING AS CLINICAL BRAIN DEATH, A CASE SERIES

Guillain-Barré Syndrome (GBS), Miller-Fisher Syndrome (MFS), and Bickerstaff Brainstem Encephalitis (BBE) are neuroinflammatory disorders that share common immunopathogenic mechanisms. Although overlapping presentations of these conditions are rare, they pose significant diagnostic challenges, especially when mimicking clinical brain death. Objective: To present a case series of three patients who demonstrated an overlap of GBS, MFS, and BBE, with all patients exhibiting profound neurological impairments, including clinical signs of brain death. Methods: A retrospective review of three cases admitted to the ICU over the last three years was conducted. Detailed clinical profiles, cerebrospinal fluid (CSF) analysis, nerve conduction studies (NCS), and electromyography (EMG) results were reviewed. All patients were treated with intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (TPE). Results: All three patients had a history of preceding infections and were presented with ophthalmoplegia, ataxia, and altered levels of consciousness, progressing to coma. CSF analysis revealed albuminocytological dissociation, and NCS/EMG indicated severe polyneuropathy. Two patients responded positively to IVIG and plasmapheresis, showing significant neurological recovery, while the third patient demonstrated a delayed but spontaneous recovery. All patients eventually achieved full or near-full neurological recovery. Conclusions: This case series highlights the clinical continuum and diagnostic complexity of overlapping GBS, MFS, and BBE, particularly in presentations mimicking brain death. Early recognition and prompt immunomodulatory therapy are crucial in improving patient outcomes, even in cases with severe neurological deficits. Further research is warranted to elucidate pathophysiology and optimize treatment strategies for overlapping neuroinflammatory syndromes.

Efficacy of butylphthalide in the treatment of patients with stroke attributed to intracranial arterial stenosis.

To explore the clinical efficacy of butylphthalide in treating patients with stroke attributed to intracranial artery stenosis (ICAS). In this retrospective study, records of 163 patients with stroke attributed to ICAS admitted to Jiaxing Second Hospital from January 2021 to January 2023 were retrospectively analyzed. Patients were divided into two groups based on the treatment received: control group (patients received routine treatment, n=55) and observation group (patients treated with butylphthalide on a routine basis, n=58). Changes in levels of cerebrovascular reactivity (CVR), breath-holding index (BHI), pulsatility index (PI), and middle cerebral artery mean flow velocity (Vm) between the two groups before and after treatment were compared. In addition, cognitive function, neurological function, and living ability were compared between the two groups before and after treatment, as well as the overall clinical efficacy of the treatment. The baseline data was comparable between the two groups (P>0.05). After the treatment, CVR, BHI, and Vm indicators in the observation group were significantly higher than those in the control group, while the levels of PI indexes were significantly lower than those in the control group (P<0.05). Montreal Cognitive Assessment (MoCA) and Barthel scale scores of the observation group were significantly higher compared to the control group, while the scores of National Institutes of Health Stroke Scale (NIHSS) were significantly lower (P<0.05). Butylphthalide in addition to routine treatment can effectively improve cerebrovascular reserve function, promote neurological and cognitive dysfunction recovery, and enhance daily living ability of patients with stroke caused by ICAS.

Long-term outcome and predictors of neurological recovery in cervical spinal cord injury: a population-based cohort study

This retrospective study analyzed prognostic factors for neurological improvement and ambulation in 194 adult patients (≥ 15 years) with traumatic cervical spinal cord injuries treated at the neurological SCI unit (SCIU) at the Karolinska University Hospital Stockholm, Sweden, between 2010 and 2020. The primary outcome was American spinal injury association impairment scale (AIS) improvement, with secondary focus on ambulation restoration. Results showed 41% experienced AIS improvement, with 51% regaining ambulation over a median follow-up of 3.7 years. Significant AIS improvement (p < 0.001) and reduced bladder/bowel dysfunction (p < 0.001) were noted. Multivariable analysis identified initial AIS C-D (< 0.001), central cord syndrome (p = 0.016), and C0–C3 injury (p = 0.017) as positive AIS improvement predictors, while lower extremity motor score (LEMS) (p < 0.001) and longer ICU stays (p < 0.001) were negative predictors. Patients with initial AIS C-D (p < 0.001) and higher LEMS (p < 0.001) were more likely to regain ambulation. Finally, older age was a negative prognostic factor (p = 0.003). In conclusion, initial injury severity significantly predicted neurological improvement and ambulation. Recovery was observed even in severe cases, emphasizing the importance of tailored rehabilitation for improved outcomes.

Cervical Disc Arthroplasty Device Failure Causing Progressive Cervical Myelopathy and Requiring Revision Cervical Corpectomy.

Cervical disc arthroplasty is a well-established alternative to anterior cervical fusion but requires precise placement for optimal outcomes. We present the case of a 2-level cervical disc arthroplasty with suboptimal implantation of the interbody devices, requiring revision corpectomy. Supplemental video, Supplemental Digital Content 1 (http://links.lww.com/CLINSPINE/A358) content of the revision surgery is also provided. This report highlights the importance of proper implant sizing and position and reviews the nuances of surgical revision. A retrospective review of the clinical and radiographic data was performed from prior to the index operation through the 3-month postoperative period after the surgical revision. The patient presented approximately 2 years post-cervical arthroplasty with increasing neck pain and early cervical myelopathy. An imaging workup revealed severe cervical stenosis at the caudal level with cord compression and concern for device failure. Intraoperatively, the core of the caudal device was found to have ejected into the spinal canal. A cervical corpectomy of the intervening vertebra with the removal of both devices was performed. The patient had a complete neurologic recovery. Although failure of a cervical disc arthroplasty device is rare, the likelihood can be significantly increased with poor sizing (over or under sizing), asymmetric placement, endplate violation, or poor patient selection. In the case presented herein, early device failure was unrecognized, and the patient went on to develop progressive cervical myelopathy requiring revision corpectomy.

Chemerin 15 peptide reduces neuroinflammation via the ChemR23 receptor after ischemia-reperfusion injury.

Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke; consequently, understanding its regulation could facilitate the development of therapies for ischemic stroke. Chemerin 15, a 15-amino acid peptide derived from chemerin, exerts powerful anti-inflammatory effects through ChemR23, modulates macrophage polarization, and diminishes inflammatory cytokine expression in peripheral inflammation models. However, its effects on microglia and stroke remain unclear. In this study, we used an in vitro oxygen/ glucose deprivation BV2 cell model and a mouse model of ischemia-reperfusion injury to investigate the role of chemerin 15 in stroke and the underlying mechanisms. We co-cultured BV2 microglial cells with HT-22 hippocampal neurons and observed that chemerin 15 reduced apoptosis in HT-22 cells. Furthermore, we found that chemerin 15 binds to the ChemR23 receptor on the cell surface, inducing its internalization. This process regulated the activity of adenosine 5'-monophosphate-activated protein kinase and inhibited its downstream target nuclear factor kappa B. These effects could be reversed by treatment with α-NETA, a ChemR23 inhibitor. In mice with ischemia-reperfusion injury, chemerin 15 modulated microglial polarization, reduced infarct volume and neuronal apoptosis, and facilitated cognitive and neurological function recovery. Our findings suggest that chemerin 15 suppresses the microglia-mediated inflammatory response, decreases neuronal apoptosis, and enhances long-term neurological function recovery by inducing ChemR23 internalization and regulating the adenosine 5'-monophosphate-activated protein kinase/nuclear factor kappa B signaling pathway.

Assessment of long-term psychosocial outcomes in N-methyl-D-aspartate receptor encephalitis – the SAPIENCE study protocol

BackgroundN-methyl-D-aspartate-receptor (NMDAR) encephalitis is a rare neurological autoimmune disease with severe neuropsychiatric symptoms during the acute phase. Despite good functional neurological recovery, most patients continue to experience cognitive, psychiatric, psychological, and social impairments years after the acute phase. However, the precise nature and evolving patterns over time of these long-term consequences remain unclear, and their implications for the well-being and quality of life of predominantly young patients have yet to be thoroughly examined.MethodsSAPIENCE is a European multi-center (n = 3) prospective observational cohort study studying the long-term cognitive, psychiatric, psychological, and social outcome in patients with NMDAR encephalitis. The study consists of three interconnected levels. Level 1 comprises a qualitative interview and focus groups with patients and their caregivers. Level 2 consists of a condensed form of the interview, standardized questionnaires, and a detailed neuropsychological examination of patients. Level 3 involves an online survey that will be open to patients world-wide and explores patient-reported outcomes (PROMs), and patient-reported experiences (PREMs) in association with clinical and cognitive outcomes. Levels 1 to 3 will progressively contribute developing of structured interviews, survey questions, and treatment guidelines by informing one another.DiscussionSAPIENCE is an in-depth study of the long-term effects of NMDAR encephalitis and bridges the gap between standardized assessments and individual patient experiences, intending to improve patient care and to increase awareness of the psychosocial long-term consequences of the disease. Through collaboration of experts in clinical neurology and social and health psychology across Europe, SAPIENCE aims to create online assessment tools and formulate guidelines for patient-centered post-acute care that will help enhance the quality of life for patients and caregivers.

Acid sphingomyelinase inhibition induces cerebral angiogenesis post-ischemia/reperfusion in an oxidative stress-dependent way and promotes endothelial survival by regulating mitochondrial metabolism

Acid sphingomyelinase (ASM) inhibitors are widely used for the treatment of post-stroke depression. They promote neurological recovery in animal stroke models via neurorestorative effects. In a previous study, we found that antidepressants including amitriptyline, fluoxetine, and desipramine increase cerebral angiogenesis post-ischemia/reperfusion (I/R) in an ASM-dependent way. To elucidate the underlying mechanisms, we investigated the effects of the functional ASM inhibitor amitriptyline in two models of I/R injury, that is, in human cerebral microvascular endothelial hCMEC/D3 cells exposed to oxygen-glucose deprivation and in mice exposed to middle cerebral artery occlusion (MCAO). In addition to our earlier studies, we now show that amitriptyline increased mitochondrial reactive oxygen species (ROS) formation in hCMEC/D3 cells and increased ROS formation in the vascular compartment of MCAO mice. ROS formation was instrumental for amitriptyline’s angiogenic effects. ROS formation did not result in excessive endothelial injury. Instead, amitriptyline induced a profound metabolic reprogramming of endothelial cells that comprised reduced endothelial proliferation, reduced mitochondrial energy metabolism, reduced endoplasmic reticulum stress, increased autophagy/mitophagy, stimulation of antioxidant responses and inhibition of apoptotic cell death. Specifically, the antioxidant heme oxygenase-1, which was upregulated by amitriptyline, mediated amitriptyline’s angiogenic effects. Thus, heme oxygenase-1 knockdown severely compromised angiogenesis and abolished amitriptyline’s angiogenic responses. Our data demonstrate that ASM inhibition reregulates a complex network of metabolic and mitochondrial responses post-I/R that contribute to cerebral angiogenesis without compromising endothelial survival.

Effective treatment of traumatic brain injury by injection of a selenium-containing ointment

Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with 1H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells in vitro. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI. Statement of significanceTraumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI in vivo. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect.