Effect of Ischemia-Induced Cochlear Inflammation on Auditory Responses in Male Rats

Background and Aim: Ischemic injury is a major cause of hearing loss and oxidative stress is an important part of ischemic injury. The goal of this study was to evaluate the cochlear oxidative stress effect on auditory responses in male rats. Methods: Cochlear oxidative stress was induced by bilateral carotid artery occlusion for 20 minutes. The rats were evaluated by biochemical inflammatory factors tumor necrosis factor-α [TNF-α] and C-reactive protein (CRP) in the day before and 1st, 4th, and 7th days following surgery. The auditory brainstem response (ABR) and electrocochleography (ECochG) were evaluated on the day before surgery and 14th, 21th and 28th days after surgery. Results: TNF-α and CRP levels concentrations increased one day after ischemia and subsequently decreased on the 7th day. The click and tone burst evoked ABR showed increased thresholds on day14th, 21th, and 28th. The highest threshold was recorded on day14th. The ECochG results also were abnormal for 55%, 70%, and 45% of cases on day 14th, 21th, and 28th, respectively. Conclusion: Cochlear oxidative stress affects hearing sensitivity. The ABR shows elevated thresholds and abnormal ECochG was found in many cases.

Multi-Parametric Diagnostic Approach and Potential Markers of Early Onset Subclinical Cardiovascular Disease in a Cohort of Children, Adolescents and Young Adults Vertically Infected with HIV on cART

Background: HIV infection and lifelong cART are responsible of an increase in cardiovascular risk. The aim of this study was to describe the subclinical cardiovascular disease and to identify early markers of cardiovascular damage in adolescents and young adults vertically infected with HIV on cART, through an innovative multi-parametric approach. Methods: We enrolled 52 patients vertically infected with HIV. Demographic records, traditional cardiovascular risk factors, laboratory findings and echocardiographic measurements were collected in a one-year routine follow up. The echocardiographic examination included measurements of the 2D and 3D ejection fraction (EF), E/A ratio, E/E′ ratio, carotid intima media thickness (cIMT), flow-mediated dilation (FMD) and global longitudinal strain (GLS). Results: At the time of enrolment, all the patients were on cART therapy. The viral load was suppressed in 95% of them. EF was normal in 94.2% of patients (66 ± 7.2%), and GLS (mean value: −20.0 ± 2.5%) was reduced in 29% of patients. The cIMT mean value was higher than the 95th centile for sex and age in 73%, and FMD was impaired in 45% of patients. Clinically evident disease was found in three patients: dilative cardiomyopathy in one, thoracic-abdominal aneurysm Crawford type II with a bilateral carotid dilation in one and carotid plaque with 30% of stenosis in a third patient. Conclusions: This study confirms the presence of clinical and subclinical cardiovascular disease in a very young population vertically infected with HIV, underlining the importance of an early, multi-parametric cardiovascular follow up.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.

Association between Subclavian Artery Plaques and Future Cardiovascular Events in a Hypertensive Cohort

BackgroundAtherosclerosis is one of the leading contributors to cardiovascular diseases. Subclinical atherosclerosis could occur long time before the presence of clinical symptoms and may have predictive value for future cardiovascular events. Existing carotid subclinical atherosclerotic markers have limited value.Subjects and MethodsPatients admitted to the cardiac vascular center of Beijing Tiantan Hospital due to essential hypertension were prospectively consecutively enrolled. Those with histories of coronary artery disease (CAD), cerebrovascular diseases, and significant stenosis of main arteries were excluded. Patients diagnosed with carotid and/or subclavian artery stenosis were also excluded after admission. All participants received a series of routine blood test at admission into hospital and ultrasonic examinations of bilateral carotid arteries and right subclavian artery. All data were recorded. After discharged from hospital all participants were followed up with cardiovascular events, including death, hear failure, myocardial infarction, unstable angina pectoris and stroke.Results473 participants were finally involved in the study, including 284 men and 189 women.9/473 (8.2%, 95%C.I. [5.9-11.1%] participants suffered from endpoint events, including 19(4.0%) cases of myocardial infarction (15 undergoing PCI and 5 death), 4(0.8%) heart failure (all also involved in the myocardial infarction group), 3(0.6%) ischemic stroke (1 death), and 17(3.6%) angina pectoris (7 undergoing PCI). No death due to other reasons was recorded. After the adjustment of potential risk factors based on the results of univariate analyses, the prevalence of right subclavian plaque (RSP) (OR=2.428, 95%C.I. [1.098, 5.370], p=0.028) and both carotid and subclavian plaques (MPs) (OR = 3.539, 95%C.I. [1.547, 8.096], p = 0.003) were both significantly associated with endpoint events. Globulin and albumin had significantly correlations with future events despite the atherosclerotic marker used in the regression model.ConclusionThe prevalence of right subclavian plaques was independently significantly associated with the incidence of future cardiovascular events in the cohort. Higher level of globulin and lower level of albumin tended to be predictors for future events. Combination of both right subclavian artery and carotid artery atherosclerotic plaques may have strongest predictive value for future cardiovascular events in the hypertensive cohort without clinical atherosclerotic diseases.

Chronic cerebral hypoperfusion in male rats results in sustained HPA activation, and hyperinsulinemia

Vascular contributions to cognitive impairment and dementia (VCID) is a spectrum of cognitive deficits caused by cerebrovascular disease, for which insulin resistance is a major risk factor. A major cause of VCID is chronic cerebral hypoperfusion (CCH). Under stress, sustained hypothalamic-pituitary-adrenal axis (HPA) activation can result in insulin resistance. Little is known about the effects of CCH on the HPA axis. We hypothesized that CCH causes sustained HPA activation and insulin resistance. Male rats were subjected to bilateral carotid artery stenosis (BCAS) for 12 weeks to induce CCH and VCID. BCAS reduced cerebral blood flow and caused memory impairment. Plasma adrenocorticotropic hormone was increased in the BCAS rats (117.2 ± 9.6 vs. 88.29 ± 9.1 pg/mL, BCAS vs. sham, p = 0.0236), as was corticosterone (220 ± 21 vs. 146 ± 18 ng/g feces, BCAS vs. sham, p = 0.0083). BCAS rats were hypoglycemic (68.1 ± 6.1 vs. 76.5± 5.9 mg/dL, BCAS vs. sham, p = 0.0072), with increased fasting insulin (481.6 ± 242.6 vs. 97.94± 40.02 pmol/L, BCAS vs. sham, p = 0.0003) indicating BCAS rats were insulin resistant (HOMA-IR:11.71 ± 6.47 vs. 2.62 ± 0.93; BCAS vs. control, p = 0.0008). Glucose tolerance tests revealed that BCAS rats had lower blood glucose AUCs than controls (250 ± 12 vs. 326 ± 20 mg/dL/h, BCAS vs. sham, p = 0.0075). These studies indicate that CCH causes sustained activation of the HPA and results in insulin resistance, a condition that is expected to worsen VCID.