Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model.

BACKGROUND AND PURPOSE: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. METHODS: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. RESULTS: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P=0.008). CONCLUSIONS: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Contemplating IL-6, a double-edged sword cytokine: Which side to use for stroke pathology?

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points.

Getting the guts to expand stroke treatment: The potential for microbiome targeted therapies.

AIMS: This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke. DISCUSSION: Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke. Additionally, hyperglycemic conditions may play a significant role in worsening stroke outcomes due to microbiome dysbiosis. CONCLUSION: Recent research has illuminated the vital role of the GBA in propagating poor clinical outcomes, such as hemorrhagic transformation, following ischemic stroke. Considering this detrimental consequence of stroke, and the apparent role of the GBA role, future therapeutics should aim to mitigate this peripheral contribution to stroke complications.

IL-6 in spinal cord injury: could immunomodulation replace immunosuppression in the management of acute traumatic spinal cord injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Using Frailty Measures to Predict Functional Outcomes and Mortality After Type II Odontoid Fracture in Elderly Patients: A Retrospective Cohort Study.

STUDY DESIGN: Single-center retrospective cohort study. OBJECTIVES: Type II odontoid fractures occur disproportionately among elderly populations and cause significant morbidity and mortality. It is a matter of debate whether these injuries are best managed surgically or conservatively. Our goal was to identify how treatment modalities and patient characteristics correlated with functional outcome and mortality. METHODS: We identified adult patients (>60 years) with traumatic type II odontoid fractures. We used multivariate regression controlling for patient demographics, Glasgow Coma Scale (GCS) score, Charlson Comorbidity Index (CCI), modified Rankin Scale (mRS) score, modified Frailty Index (mFI-5 and mFI-11), fracture displacement, and conservative vs operative treatment. RESULTS: Of the 59 patients (mean age 77.9 years), 24 underwent surgical intervention and 35 underwent conservative management. Operatively managed patients were younger (73.4 vs 80.6 years, P < .001) and had higher degree of fracture displacement (3.5 vs 1.0 mm, P = .002) than conservatively managed patients but no other differences in baseline characteristics. Twenty-four patients (40.7%) died within the study period (median time to death: 376 days). There were no differences between treatment groups in functional outcomes (mRS or Frankel Grade) or mortality (33.3% in operative group vs 45.7%, P = .34). There was a statistically significant correlation between higher presentation mRS score and subsequent mortality on multivariate analysis (OR = 2.06, 95% CI 1.04-4.10, P = .039), whereas surgical intervention, age, GCS score, CCI, mFI-5, mFI-11, sex, and fracture displacement were not significantly correlated. CONCLUSIONS: Mortality after type II odontoid fractures in elderly patients is common. mRS score at presentation may help predict mortality more accurately than other patient factors.

Differences in postoperative quality of life in young, early elderly, and late elderly patients undergoing surgical treatment for degenerative cervical myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common progressive spine disorder affecting predominantly middle-aged and elderly populations. With increasing life expectancy, the incidence of CSM is expected to rise further. The outcomes of elderly patients undergoing CSM surgery and especially their quality of life (QOL) postoperatively remain undetermined. This study retrospectively reviewed patients to identify baseline differences and validated postoperative patient-reported outcome (PRO) measures in elderly patients undergoing CSM surgery. METHODS: The multi-institutional, neurosurgery-specific NeuroPoint Quality Outcomes Database was queried to identify CSM patients treated surgically at the 14 highest-volume sites from January 2016 to December 2018. Patients were divided into three groups: young (< 65 years), early elderly (65-74 years), and late elderly (≥ 75 years). Demographic and PRO measures (Neck Disability Index [NDI] score, modified Japanese Orthopaedic Association [mJOA] score, EQ-5D score, EQ-5D visual analog scale [VAS] score, arm pain VAS, and neck pain VAS) were compared among the groups at baseline and 3 and 12 months postoperatively. RESULTS: A total of 1151 patients were identified: 691 patients (60%) in the young, 331 patients (28.7%) in the early elderly, and 129 patients (11.2%) in the late elderly groups. At baseline, younger patients presented with worse NDI scores (p < 0.001) and lower EQ-5D VAS (p = 0.004) and EQ-5D (p < 0.001) scores compared with early and late elderly patients. No differences among age groups were found in the mJOA score. An improvement of all QOL scores was noted in all age groups. On unadjusted analysis at 3 months, younger patients had greater improvement in arm pain VAS, NDI, and EQ-5D VAS compared with early and late elderly patients. At 12 months, the same changes were seen, but on adjusted analysis, there were no differences in PROs between the age groups. CONCLUSIONS: The authors' results indicate that elderly patients undergoing CSM surgery achieved QOL outcomes that were equivalent to those of younger patients at the 12-month follow-up.

Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage.

Early brain injury (EBI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia (DCI) are common complications of subarachnoid hemorrhage (SAH). Inflammatory processes in the cerebrospinal fluid (CSF) are one of the causes for such complications. Our aim to study the effects of an IL-6 receptor antagonist (Tocilizumab) examines the occurrence of DCVS, neuronal cell death, and microclot formation in an acute SAH rabbit model. Twenty-nine New Zealand white rabbits were randomized into one of three groups as the SAH, SAH + Tocilizumab, and sham groups. In SAH groups, hemorrhage was induced by extracranial-intracranial arterial blood shunting from the subclavian artery into the cisterna magna under intracranial pressure (ICP) monitoring. In the second group, Tocilizumab was given once intravenously 1 h after SAH induction. Digital subtraction angiography was performed, and CSF and blood were sampled before and after (day 3) SAH induction. IL-6 plasma and CSF levels were measured. TUNEL, FJB, NeuN, and caspase-3 immunostaining were used to assess cell apoptosis, neurodegeneration, and neuronal cell death, respectively. Microclot formation was detected by fibrinogen immunostaining. Between baseline and follow-up, there was a significant reduction of angiographic DCVS (p < 0.0001) in the Tocilizumab compared with the SAH group. Tocilizumab treatment resulted in decreased neuronal cell death in the hippocampus (p = 0.006), basal cortex (p = 0.001), and decreased microclot formation (p = 0.02). Tocilizumab reduced DCVS, neuronal cell death, and microclot formation in a rabbit SAH model, and could be a potential treatment to prevent DCVS and DCI in SAH patients.