The Artery of Wollschlaeger and Wollschlaeger (AWW) is a non-eloquent, tentorial branch of the superior cerebellar artery (SCA). Coursing posteriorly from an intradural origin, the AWW passes through the ambient cistern and supplies the medial tentorium. Due to its small diameter, the AWW is often only identified in the context of secondary dilation from pathologies such as dural arteriovenous fistulas (DAVF). Herein, we report the first case, to our knowledge, of an aneurysm of the AWW associated with a posterior fossa DAVF Swift identification and diagnosis followed by cautious treatment of both the aneurysm and fistula were critical to avert rupture and optimize outcomes, avoiding potential hemorrhagic complications.
BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a major cause of stroke with a high rate of re-occlusion following mechanical thrombectomy (MT). Among the available rescue options, glycoprotein IIb/IIIa inhibitors (GPI) have shown promise as a potential therapeutic strategy. This systematic review and meta-analysis examine studies exploring the use of glycoprotein inhibitors as a first-line treatment for refractory occlusion or high-grade stenosis following EVT in the setting of ICAD. METHODS: A systematic review and meta-analysis were performed. Studies using GPI as the first-line rescue treatment (GPI-rt) after failed thrombectomy or in the setting with high-grade stenosis (>50%) were included. The primary outcome of interest was good clinical outcomes (defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days). Secondary outcomes of interest were successful recanalization (TICI 2b-3), symptomatic intracranial hemorrhage (sICH), and mortality by 90 days. RESULTS: Our study processed 2111 articles, which yielded eight relevant studies for review, four single and four double arm. These studies comprised 763 patients, divided into GPI-rt (535 patients) and non-GPI-rt (228 patients) cohorts. The GPI-rt group had higher rates of mRS ≤ 2 at 90 days (58.5% vs 38.9%, p = 0.002) and lower mortality rates (7.8% vs 17.5%, p = 0.04) compared to the non-GPI-rt cohort. mTICI 2b-3 rates and rates of sICH were not significantly different between the cohorts. CONCLUSIONS: First line GPI-rt demonstrates significant clinical benefit and significantly lower mortality without a rise in rates of sICH. GPI are a potential first line rescue treatment of ICAD.
BACKGROUND: Posterior cerebral arteries with acute ischemic strokes (PCA-AISs) comprise around 2% of all acute ischemic strokes and may result in significant long-term deficits. Current guidance regarding endovascular thrombectomy (EVT) for PCA-AIS is insufficient as no published randomized trials exist. METHODS: An analysis of the National Inpatient Sample database compared medical management versus EVT for PCA-AIS. Propensity score matching was applied to adjust for nonrandomization. RESULTS: The study included 19,655 patients. Before matching, the EVT cohort had significantly higher National Institutes of Health Stroke Scale (NIHSS) (10.21 vs. 4.67, p < 0.001), had lower rates of favorable functional outcomes, functional independence, and higher rates of intracranial hemorrhage (ICH) and inpatient mortality. After matching, no differences in functional outcomes were identified, but revealed a higher proportion of ICH in the EVT group (17.45% vs. 8.98%, p < 0.001). However, NIHSS subgroup analysis identified improved functional outcomes associated with the EVT group who presented with an NIHSS between 10 and 19 both in terms of rates of favorable functional outcomes (35.56% vs. 12.09%, p < 0.001) and rates of functional independence (26.67% vs. 9.34%, p < 0.01). On further investigation, the clinical benefit, in the NIHSS 10-19 subgroup, was driven by patients receiving EVT in combination with intravenous thrombolysis (IVT). CONCLUSIONS: This analysis shows that current national practices utilize EVT for more severe PCA strokes. Clinical benefit was only detected in patients with moderate stroke severity (NIHSS 10-19) who were treated with combined EVT and IVT. Further work is needed to investigate the features of PCA-AIS that might benefit from EVT the most.
OBJECTIVE: Congenital intracranial pial arteriovenous fistula (PAVF) is a rare cerebral vascular pathology characterized by a direct shunt between one or more pial feeding arteries and a cortical draining vein. Transarterial endovascular embolization (TAE) is widely considered first line therapy. Curative TAE may not be achievable in the multihole variant due to the potential to harbor innumerable small feeding arteries. Transvenous embolization (TVE) may be considered to target the final common outlet of the lesion. Here, we present a series of four patients with complex multi-hole congenital PAVF treated with staged TAE followed by TVE. METHODS: A retrospective review was conducted on patients who underwent treatment for congenital, multi-hole PAVFs treated by a combined TAE/TVE approach at our institution since 2013. RESULTS: We identified four patients with multi-hole PAVF treated by a combined TAE/TVE. Median age was 5.2 (0-14.7) years. Median follow-up of 8 (1-15) months by catheter angiography and 38 (23-53) months by MRI/MRA was obtained. TVE achieved complete occlusion in three patients that proved durable on radiographic follow-up and demonstrated excellent clinical outcomes with a modified Rankin Score (mRS) of 0 or 1. Complete occlusion of the draining vein was not achieved by TVE in one case. This patient is graded as pediatric mRS=5 three years post-procedure. CONCLUSIONS: With thorough technical considerations, our series indicates that TVE of multi-hole PAVF that are refractory to TAE is feasible and effective in arresting the consequences of chronic, high-flow AV shunting produced by this pathology.
BACKGROUND: The Surpass Streamline flow diverter (SSFD) possesses 4 attributes that may offer an important advantage in the treatment of complex pathologies: (1) utilization of an over-the-wire (OTW) delivery system, (2) greater device length, (3) larger potential diameter, and (4) propensity to open in tortuosity. OBSERVATIONS: Case 1 leveraged device diameter to embolize a large, recurrent vertebral artery aneurysm. Angiography at 1 year posttreatment showed complete occlusion with a patent SSFD. Case 2 leveraged device length and opening in tortuosity to manage a symptomatic 20-mm cavernous carotid aneurysm. Magnetic resonance imaging at 2 years demonstrated aneurysm thrombosis and patent stents. Case 3 utilized diameter, length, and the OTW delivery system to treat a giant intracranial aneurysm previously treated with surgical ligation and a high-flow bypass procedure. Angiography at 5 months postprocedure demonstrated the return of laminar flow, as the vein graft had healed around the stent construct. Case 4 used diameter, length, and the OTW system to treat a giant, symptomatic, dolichoectatic vertebrobasilar aneurysm. Twelve-month follow-up imaging revealed a patent stent construct with no change to the aneurysm size. LESSONS: Increased awareness of the unique attributes of the SSFD may allow a larger number of cases to be treated with the proven mechanism of flow diversion.
BACKGROUND: Cerebral hyperperfusion syndrome (CHS) occurs after the restoration of blood flow to a previously low-flow, low-pressure region of the cerebral vasculature, which subsequently responds with chronic compensatory vasodilation, leading to a dysregulated state. Sudden restoration of normal blood flow can overwhelm the vasculature leading to intracranial hemorrhage (ICH). Separately, the Windkessel phenomenon describes the capacity for elastic vessels to expand with systolic pressure and decompress with diastole, thereby suppressing distal pulse pressure. We encountered a case involving giant basilar aneurysms in which we believe the Windkessel phenomenon precipitated a catastrophic manifestation of CHS at treatment. OBSERVATION: We present a 60-year-old female found to have marked dolichoectasia of the right cervical internal carotid, vertebral, and basilar arteries concurrent with two large vertebrobasilar dissecting-type fusiform aneurysms. Managed conservatively for ten years before developing gait ataxia, new imaging revealed dramatic interval growth of the larger aneurysm. Flow diversion with partial coiling of the aneurysms was pursued. The patient suffered intra-procedural catastrophic thalamic and midbrain hemorrhage with intraventricular extension. A meticulous review of the case data was undertaken. Our findings suggest that giant aneurysms can act as a Windkessel reservoir, depressing the distal pulse pressure. Flow diversion bypasses the reservoir, increasing the distal pulse pressure beyond the autoregulatory capacity, resulting in ICH analogous to CHS. LESSONS: CHS and Windkessel phenomenon can contribute to catastrophic sequelae in the treatment of giant intracranial aneurysms with flow diversion. Awareness of this mechanism can protect future patients from harm.
Basilar artery aneurysms account for approximately 5% of all intracranial aneurysms. This bibliometric analysis summarizes the most-cited articles on basilar artery aneurysms and highlights the contributing articles to today's evidence-based practice. In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "basilar artery aneurysm" or "basilar aneurysm" was used. Our results were arranged in descending order based on the article's citation count. The 100 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact Per Paper (SNIP), and Hirsch index. The keyword-based search showed that 699 articles were published between 1888 and 2022. The top 100 articles were published between 1961 and 2019. The top 100 most cited articles collected a total of 8869 citations with an average of 89 citations per paper. The rate of self-citations accounted for an average of 4.85% of the total number of citations. The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in basilar artery aneurysms by finding the top 100 most cited papers.
Intracranial Aneurysm , Humans , Intracranial Aneurysm/surgery , Basilar Artery , Bibliometrics , Publications , Databases, Factual
OBJECTIVE: This study aims to systematically review the management and outcomes of pediatric patients who develop intracranial pseudoaneurysm (IPA) following head trauma or iatrogenic injury. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Additionally, a retrospective analysis was conducted on pediatric patients who underwent evaluation and endovascular treatment for IPA originating from head trauma or iatrogenic injury at a single institution. RESULTS: Two hundred twenty-one articles in the original literature search. Fifty-one met inclusion criteria resulting in a total of 87 patients with 88 IPAs including our institution. Patients ranged in age from 0.5 months to 18 years. Parent vessel reconstruction was used as first-line treatment in 43 cases, parent vessel occlusion in 26, and direct aneurysm embolization (DAE) in 19. Intraoperative complications were observed in 3.00% of procedures. Complete aneurysm occlusion was achieved in 89.61% of cases. 85.54% of cases resulted in favorable clinical outcomes. The mortality rate after treatment was 3.61%. The DAE group had higher rates of aneurysm recurrence than other treatment strategies (P = 0.009). Patients with SAH had overall worse outcomes compared to patients who did not (P = 0.024). There were no differences in favorable clinical outcomes (P = 0.274) or complete aneurysm occlusion (P = 0.13) between primary treatment strategies. CONCLUSIONS: IPAs were successfully obliterated, and favorable neurological outcomes were achieved at a high rate regardless of primary treatment strategy. DAE had a higher rate of recurrence than the other treatment groups. Each described treatment method in our review is safe and viable for the treatment of IPAs in pediatric patients.
Aneurysm, False , Aneurysm , Craniocerebral Trauma , Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Humans , Child , Retrospective Studies , Aneurysm, False/diagnostic imaging , Aneurysm, False/etiology , Aneurysm, False/surgery , Treatment Outcome , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Craniocerebral Trauma/complications , Aneurysm/complications , Iatrogenic Disease , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery
Introduction: The authors investigated a novel functional pain scale, the Activity-Based Checks (ABCs) of Pain, following open urologic surgery. The primary objectives were to establish the strength of the correlation between the ABCs and the numeric rating scale (NRS) and determine the impact of functional pain on the patient's opioid requirements. We hypothesized that ABC score would correlate strongly with NRS and that the ABC score during hospitalization would be more closely correlated with the number of opioids prescribed and used. Methods: This prospective study included patients at a tertiary academic hospital undergoing nephrectomy and cystectomy. The NRS and ABCs were collected pre-operatively, during the inpatient stay, and at the one-week follow-up. Milligrams of morphine equivalents (MMEs) prescribed at discharge and the MME reportedly taken during the first post-operative week were recorded. Spearman's Rho was used to assess the correlation between scale variables. Results: Fifty-seven patients were enrolled. The ABCs correlated strongly with the NRS at baseline and post-operative appointments (r = 0.716, p < 0.001 and 0.643, p < 0.001). Neither the NRS nor the composite ABCs score was predictive of outpatient MME requirements; the ABCs function, "Walking outside the room" significantly correlated to MMEs taken after discharge (r = 0.471, p = 0.011). The greatest predictor of MMEs taken was the number of MMEs prescribed (0.493, p = 0.001). Conclusions: This study highlighted the importance of post-operative pain assessment that takes functional pain into consideration to evaluate pain, inform management decisions, and reduce opiate reliance. It also emphasized the strong relationship between opioids prescribed and opioids consumed.
OBJECTIVE: External ventricular drains (EVDs) are commonly used to remove cerebrospinal fluid and monitor intracranial pressure in patients with neurological dysfunction. Often the first invasive procedure learned in training, ventricular drain placement is the quintessential neurosurgical procedure. This bibliometric analysis highlights the top contributing EVD articles in current evidence-based practice. METHODS: The Scopus database was used to perform a title-specific, keyword-based search for all publications until September 2022. The keywords "external ventricular drain" or "EVD" or "external ventriculostomy" were used. The 50 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index. RESULTS: The keyword-based search showed that 8464 articles on EVDs were published between 1991 and 2022. The top 50 articles were published between 1999 and 2019. The top 50 articles acquired a total of 3343 citations with an average of 66.86 citations per paper. The rate of self-citations accounted for an average of 5.16% of the total number of citations. A majority of the top 50 articles focused on EVD infection and placement accuracy. The first and second most cited papers were authored by Zabramski et al and Fried et al, respectively. CONCLUSIONS: The bibliometric analysis provides a quantitative overview of how topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in EVDs by analyzing the top 50 most cited papers.
Bibliometrics , Medicine , Humans , Publications , Neurosurgical Procedures , Intracranial Pressure
OBJECTIVE: Aneurysms located on the middle cerebral artery (MCA) range from 22% to 31.5% in prevalence of all aneurysms in the anterior cerebral circulation. This bibliometric analysis summarizes the most cited articles on MCA aneurysms and highlights the landmark publications that contributed to evidence-based practice. METHODS: In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "(middle cerebral artery OR MCA) AND aneurysm" was used. Our results were arranged in descending order based on the citation count of the article. The 100 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index. RESULTS: The keyword-based search showed that 1206 articles on MCA aneurysms were published up to August 2022. The top 100 articles were published between 1940 and 2019. The top 100 most cited articles collected a total of 6232 citations with an average of 62.3 citations per article. The rate of self-citations accounted for an average of 5.75% of the total number of citations. CONCLUSIONS: The bibliometric analysis provides a quantitative overview of how medical literature and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in research regarding MCA aneurysms by finding the top 100 most cited articles.
Intracranial Aneurysm , Medicine , Humans , Middle Cerebral Artery , Bibliometrics , Publications
OBJECTIVE: Cerebral cavernous malformations (CCMs) or cavernomas, are low-flow sinusoidal vascular anomalies of the central nervous system comprised of capillary networks filled with blood in various stages of thrombosis. This bibliometric analysis summarizes the most-cited articles on CCM and highlights the contributing articles to today's evidence-based practice. METHODS: In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until June 2022. The keyword "cerebral cavernous malformations" OR "cerebral cavernous hemangioma" OR "cerebral cavernous angioma" OR "cerebral cavernoma." was used. Our results were arranged in descending order based on the article's citation count. The 100 most-cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index were collected. RESULTS: The keyword-based search showed that 806 articles were published between 1974 and 2022 on CCMs. The top 100 articles were published between 1980 and 2018. The top 100 most cited articles collected a total of 12,928 citations with an average of 129.3 citations per paper. The rate of self-citations accounted for an average of 2.79% of the total number of citations. CONCLUSIONS: The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in CCMs by analyzing the top 100 most cited papers.
Hemangioma, Cavernous, Central Nervous System , Medicine , Humans , Bibliometrics , Publications
BACKGROUND: The goal of this study was to systematically review the management and outcomes of patients who developed pseudoaneurysm (PA) after carotid endarterectomy (postendarterectomy PA [PEPA]). METHODS: Following the PRISMA guidelines, a systematic literature review was performed using PubMed, Scopus, and Web of Science databases from date of inception to June 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective review was conducted of patients who underwent neurosurgical evaluation of suspected PEPA at our institution. RESULTS: Of the 321 articles in the original literature search, 62 were selected. A total of 143 patients (93 men, 27 women; mean age, 70.7 years) diagnosed with PEPA were included. Mean time from carotid endarterectomy to PA diagnosis was 41.8 months. Primary repair data were available for 135 patients, including 19 with primary closures, 112 with patch or graft repairs, and 4 with eversion procedures. Fifty-five patients with PA (39%) presented with infection. Staphylococcal species were the most common causative organism. Of infected PAs, 89.1% were treated with open procedures. Overall complication rates of PAs treated via open, endovascular, and hybrid methods were 31%, 15.4%, and 0%, respectively. Open ligation (42.9%) and aneurysmectomy with grafting (36.4%) resulted in the highest rates of complications. CONCLUSIONS: Despite higher complication rates after open repair strategies, use of these techniques remains a viable option in situations requiring removal of infected patches or evacuation of large extravascular collections. Endovascular treatment options are associated with low numbers of complications and can be considered for primary PEPA treatment when infection is not present.
Aneurysm, False , Blood Vessel Prosthesis Implantation , Carotid Stenosis , Endarterectomy, Carotid , Male , Humans , Female , Aged , Endarterectomy, Carotid/adverse effects , Aneurysm, False/diagnostic imaging , Aneurysm, False/etiology , Aneurysm, False/surgery , Blood Vessel Prosthesis Implantation/methods , Retrospective Studies , Treatment Outcome , Carotid Stenosis/surgery
Early life stress exposure significantly increases the risk of developing chronic pain syndromes and comorbid mood and metabolic disorders later in life. Structural and functional changes within the hippocampus have been shown to contribute to many early life stress-related outcomes. We have previously reported that adult mice that underwent neonatal maternal separation (NMS) exhibit urogenital hypersensitivity, altered anxiety- and depression-like behaviors, increased adiposity, and decreased gene expression and neurogenesis in the hippocampus. Here, we are using magnetic resonance imaging and spectroscopy (MRI and MRS) to further investigate both NMS- and acute stress-induced changes in the hippocampus of female mice. Volumetric analysis of the whole brain revealed that the left hippocampus of NMS mice was 0.038 mm3 smaller compared to naïve mice. MRS was performed only on the right hippocampus and both total choline (tCho) and total N-acetylaspartate (tNAA) levels were significantly decreased due to NMS, particularly after WAS. Phosphoethanolamine (PE) levels were decreased in naïve mice after WAS, but not in NMS mice, and WAS increased ascorbate levels in both groups. The NMS mice showed a trend toward increased body weight and body fat percentage compared to naïve mice. A significant negative correlation was observed between body weight and phosphocreatine levels post-WAS in NMS mice, as well as a positive correlation between body weight and glutamine for NMS mice and a negative correlation for naïve mice. Together, these data suggest that NMS in mice reduces left hippocampal volume and may result in mitochondrial dysfunction and reduced neuronal integrity of the right hippocampus in adulthood. Hippocampal changes also appear to be related to whole body metabolic outcomes.
Purpose of the ArticleCerebral proliferative angiopathy (CPA) is a rare and recently characterized vascular malformation that is often mistaken for a large, diffuse arteriovenous malformation (AVM). However, distinguishing the two entities is critical, as while the diseases may appear similar on imaging, they are completely different entities. The most distinguishing features of CPA compared to AVM are the presence of normal functioning brain within the 'nidus' of the abnormality and the proliferative nature of the nidus. While the management of AVM is considered well understood, the management of CPA is unclear. Typical treatment may include conservative management, targeted embolization, and/or surgical revascularization.Materials and MethodsHere, we present a patient who was initially diagnosed with a large, diffuse AVM in the posterior fossa. Initially managed conservatively, the development of progressive, debilitating neurologic symptoms prompted treatment. We pursued staged endovascular intervention and improved her initial outlook. Thereafter, volume-staged stereotactic radiosurgery (VS-SRS) was pursued to attempt to achieve a definitive treatment.Results and ConclusionsUltimately, while the treatment proved successful clinically and radiographically, the post-treatment course was exceptionally challenging. In retrospect, it is clear the working diagnosis was incorrect, and CPA was the true diagnosis. To our knowledge, this is the first known application of this treatment approach for CPA. However, the post-treatment course and final clinical outcome likely reflect the important differences between AVM and CPA. For these reasons, we are cautious to recommend the treatment course as prescribed in this case but hope to highlight important lessons learned in managing this rare condition.
Migraine is a complex neurological disorder that affects three times more women than men and can be triggered by endogenous and exogenous factors. Stress is a common migraine trigger and exposure to early life stress increases the likelihood of developing chronic pain disorders later in life. Here, we used our neonatal maternal separation (NMS) model of early life stress to investigate whether female NMS mice have an increased susceptibility to evoked migraine-like behaviors and the potential therapeutic effect of voluntary wheel running. NMS was performed for 3 h/day during the first 3 weeks of life and initial observations were made at 12 weeks of age after voluntary wheel running (Exercise, -Ex) or sedentary behavior (-Sed) for 4 weeks. Mast cell degranulation rates were significantly higher in dura mater from NMS-Sed mice, compared to either naïve-Sed or NMS-Ex mice. Protease activated receptor 2 (PAR2) protein levels in the dura were significantly increased in NMS mice and a significant interaction of NMS and exercise was observed for transient receptor potential ankyrin 1 (TRPA1) protein levels in the dura. Behavioral assessments were performed on adult (>8 weeks of age) naïve and NMS mice that received free access to a running wheel beginning at 4 weeks of age. Facial grimace, paw mechanical withdrawal threshold, and light aversion were measured following direct application of inflammatory soup (IS) onto the dura or intraperitoneal (IP) nitroglycerin (NTG) injection. Dural IS resulted in a significant decrease in forepaw withdrawal threshold in all groups of mice, while exercise significantly increased grimace score across all groups. NTG significantly increased grimace score, particularly in exercised mice. A significant effect of NMS and a significant interaction effect of exercise and NMS were observed on hindpaw sensitivity following NTG injection. Significant light aversion was observed in NMS mice, regardless of exercise, following NTG. Finally, exercise significantly reduced calcitonin gene-related peptide (CGRP) protein level in the dura of NMS and naïve mice. Taken together, these findings suggest that while voluntary wheel running improved some measures in NMS mice that have been associated with increased migraine susceptibility, behavioral outcomes were not impacted or even worsened by exercise.
Inflammation plays a key role in the progression and maintenance of chronic pain, which impacts the lives of millions of Americans. Despite growing evidence that chronic pain can be improved by treating underlying inflammation, successful treatments are lacking and pharmaceutical interventions are limited due to drug side effects. Here we are testing whether a 'healthy human' diet (HHD), with or without anti-inflammatory components (HHAID), improves pain-like behaviors in a preclinical model of chronic widespread hypersensitivity induced by neonatal maternal separation (NMS). The HHD and HHAID are isocaloric and macronutrient-matched, have a low glycemic index, and fat content (35 kcal%) that is high in omega-3 fatty acids, while only the HHAID includes a combination of key anti-inflammatory compounds, at clinically relevant doses. Mice on these diets were compared to mice on a control diet with a macronutrient composition commonly used in rodents (20% protein, 70% carbohydrate, 10% fat). Our results demonstrate a benefit of the HHAID on pain-like behaviors in both male and female mice, despite increased caloric intake, adiposity, and weight gain. In female mice, HHAID specifically increased measures of metabolic syndrome and inflammation compared to the HHD and control diet groups. Male mice were susceptible to worsening metabolic measures on both the HHAID and HHD. This work highlights important sexual dimorphic outcomes related to early life stress exposure and dietary interventions, as well as a potential disconnect between improvements in pain-like behaviors and metabolic measures.
Fatty Acids, Omega-3 , Hyperalgesia , Animals , Anti-Inflammatory Agents , Diet , Diet, High-Fat/adverse effects , Female , Hyperalgesia/drug therapy , Male , Maternal Deprivation , Mice
ABSTRACT: Patients with a history of early life stress (ELS) exposure have an increased risk of developing chronic pain and mood disorders later in life. The severity of ELS in patients with urologic chronic pelvic pain syndrome (UCPPS) is directly correlated with symptom severity and increased comorbidity, and is inversely related to likelihood of improvement. Voluntary exercise improves chronic pain symptoms, and our group and others have shown that voluntary wheel running can improve outcomes in stress-induced UCPPS models, suggesting that exercise may negate some of the outcomes associated with ELS. Here, we provide further evidence that voluntary wheel running can attenuate increased perigenital mechanical sensitivity, bladder output, and mast cell degranulation in the bladder and prostate in male mice that underwent neonatal maternal separation (NMS). Sedentary male NMS mice had reduced serum corticosterone, which was not impacted by voluntary wheel running, although stress-related regulatory gene expression in the hypothalamus and hippocampus was significantly increased after exercise. Neurogenesis in the dentate gyrus of the hippocampus was diminished in sedentary NMS mice and significantly increased in both exercised naïve and NMS mice. Sucrose consumption increased in exercised naïve but not NMS mice, and anxiety behaviors measured on an elevated plus maze were increased after exercise. Together these data suggest that voluntary wheel running is sufficient to normalize many of the UCPPS-related outcomes resulting from NMS. Exercise also increased hippocampal neurogenesis and stress-related gene expression within the hypothalamic-pituitary-adrenal axis, further supporting exercise as a nonpharmacological intervention for attenuating outcomes related to ELS exposure.
Adverse Childhood Experiences , Chronic Pain , Physical Conditioning, Animal , Animals , Humans , Hypothalamo-Hypophyseal System , Male , Maternal Deprivation , Mice , Mice, Inbred C57BL , Motor Activity , Pelvic Pain/etiology , Pelvic Pain/therapy , Pituitary-Adrenal System , Stress, Psychological/therapy
