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1.
Am J Physiol Heart Circ Physiol ; 323(6): H1343-H1351, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36367688

ABSTRACT

Mitochondrial numbers and dynamics in brain blood vessels differ between young male and female rats under physiological conditions, but how these differences are affected by stroke is unclear. In males, we found that mitochondrial numbers, possibly due to mitochondrial fission, in large middle cerebral arteries (MCAs) increased following transient middle cerebral artery occlusion (tMCAO). However, mitochondrial effects of stroke on MCAs of female rats have not been studied. To address this disparity, we conducted morphological, biochemical, and functional studies using electron microscopy, Western blot, mitochondrial respiration, and Ca2+ sparks activity measurements in MCAs of female, naïve or sham Sprague-Dawley rats before and 48 h after 90 min of tMCAO. Adverse changes in mitochondrial characteristics and the relationship between mitochondria and sarcoplasmic reticulum (SR) in MCAs were present on both sides. However, mitochondria and mitochondrial/SR associations were often within the range of normal appearance. Mitochondrial protein levels were similar between ipsilateral (ipsi) and contralateral (contra) sides. Nonrespiratory oxygen consumption, maximal respiration, and spare respiratory capacity were similar between ipsi and contra but were reduced compared with sham. Basal respiration, proton leak, and ATP production were similar among MCAs. Ca2+ sparks activity increased in sham and ipsi MCAs exposed to a mitochondrial ATP-sensitive potassium channel opener: diazoxide. Our results show that tMCAO has effects on mitochondria in MCAs on both the ipsi and contra sides. Mitochondrial responses of cerebral arteries to tMCAO in females are substantially different from responses seen previously in male rats suggesting the need for specific sex-based therapies.NEW & NOTEWORTHY We propose that differences in mitochondrial characteristics of males and females, including mitochondrial morphology, respiration, and calcium sparks activity contribute to sex differences in protective and repair mechanisms in response to transient ischemia-reperfusion.


Subject(s)
Ischemic Attack, Transient , Stroke , Female , Male , Rats , Animals , Middle Cerebral Artery , Rats, Sprague-Dawley
2.
Med Arch ; 75(2): 144-148, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34219875

ABSTRACT

BACKGROUND: In the year 2020 we observe the world adapting to "new normal" due to the COVID-19 pandemic, ways of which include physical distancing, hand hygiene, and wearing a face mask. There is no conclusive evidence about ocular manifestations of the new coronavirus infection, but cases of conjunctivitis, keratitis, and episcleritis have been reported in infected individuals. OBJECTIVE: Determining if wearing a face mask during COVID-19 pandemic causes a new onset or deterioration of previously existing dry eye disease (DED). METHODS: A prospective cohort study included 203 participants, all using surgical facemasks daily due to new regulations during COVID-19 pandemic. Participants completed a survey, containing modified Ocular Surface Disease Index (OSDI) questionnaire. They were divided into groups according to: sex, age, duration of face mask-wear, and existence of prior DED history. RESULTS: Our results indicate that women have a statistically higher OSDI score compared to men (14.4 (IQR = 2.4 - 41.7) vs. 5.0 (IQR = 0.0 - 24.4); P = .004). Age did not significantly affect OSDI median values. Group that used masks from 3 to 6 hours/day demonstrated significantly higher OSDI scores compared to <3 hour/day group (15.3 (IQR = 8.3 - 47.7) vs. 8.3 (IQR = 0.0 - 35.1); P = .001). OSDI score was significantly greater in participants with prior DED history compared to those without it (36.1 (IQR = 14.1 - 61.6) vs. 4.2 (IQR = 2.3 - 8.3); P <.001). Participants with prior DED exhibited greater worsening of their disturbances during mask wearing period compared to the ones without previous DED (54.8% vs. 17.7%, Chi-Square 28.3 DF1; P <.001), regardless of daily mask wear duration. CONCLUSION: Our study confirmed the existence of mask-associated dry eye (MADE), most profoundly in females, subjects with a history of prior DED, and if wearing a face mask lasts longer than 3 hours per day. Ophthalmologists should advise their patients of the potential ocular surface health risks related to inadequately fitted facemasks.


Subject(s)
COVID-19/prevention & control , Dry Eye Syndromes/epidemiology , Masks , Adult , Age Factors , Cohort Studies , Croatia/epidemiology , Dry Eye Syndromes/etiology , Dry Eye Syndromes/physiopathology , Female , Humans , Male , Masks/adverse effects , Middle Aged , Prospective Studies , SARS-CoV-2 , Sex Factors , Surveys and Questionnaires , Time Factors
3.
Acta Clin Croat ; 59(4): 623-631, 2020 Dec.
Article in English | MEDLINE | ID: mdl-34285433

ABSTRACT

The purpose of this research was to evaluate the relationship between general health-related quality of life (GHRQL) and sociodemographic factors in primary open-angle glaucoma (POAG) patients. A prospective cross-sectional study included 207 glaucoma patients. GHRQL was determined via two self-administered questionnaires: the 36-Item Short Form Survey (SF-36) and the EuroQol-5D (EQ-5D) questionnaire. Male and 50- to 69-year-old glaucoma patients, followed by patients who regularly used antiglaucoma therapy and those without progression of glaucoma reported a significantly higher quality of life as measured by the EQ-5D index and the EQ-5D visual analog scale (VAS) (p<0.05 all). Similarly, the Physical Component Summary (PCS) and Mental Component Summary (MCS) of SF-36 had significantly higher values for these patients (p<0.05 all). Furthermore, glaucoma patients with higher education and economic status, glaucoma patients who lived in rural areas, and those who were married achieved higher scores on EQ-5D and SF-36. In conclusion, progression of the disease, female sex, older age, lower education and economic status, urban area and unmarried status negatively affect quality of life in glaucoma patients.


Subject(s)
Glaucoma, Open-Angle , Quality of Life , Aged , Cross-Sectional Studies , Female , Glaucoma, Open-Angle/therapy , Health Status , Humans , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires
4.
Am J Physiol Heart Circ Physiol ; 317(5): H1086-H1092, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31490734

ABSTRACT

One of the major characteristics of hyperglycemic states such as type 2 diabetes is increased reactive oxygen species (ROS) generation. Since mitochondria are a major source of ROS, it is vital to understand the involvement of these organelles in the pathogenesis of ROS-mediated conditions. Therefore, we investigated mitochondrial function and ROS production in cerebral blood vessels of 21-wk-old Zucker diabetic fatty obese rats and their lean controls. We have previously shown that in the early stages of insulin resistance, and short periods of type 2 diabetes mellitus, only mild differences exist in mitochondrial function. In the present study, we examined mitochondrial respiration, mitochondrial protein expression, and ROS production in large-surface cerebral arteries. We used 21-wk-old animals exposed to peak glucose levels for 7 wk and compared them with our previous studies on younger diabetic animals. We found that the same segments of mitochondrial respiration (basal respiration and proton leak) were diminished in diabetic groups as they were in younger diabetic animals. Levels of rattin, a rat humanin analog, tended to decrease in the diabetic group but did not reach statistical significance (P = 0.08). Other mitochondrial proteins were unaffected, which might indicate the existence of compensatory mechanisms with extension of this relatively mild form of diabetes. Superoxide levels were significantly higher in large cerebral vessels of diabetic animals compared with the control group. In conclusion, prolonged dietary diabetes leads to stabilization, rather than deterioration, of metabolic status in the cerebral circulation, despite continued overproduction of ROS.NEW & NOTEWORTHY We have characterized for the first time the dynamics of mitochondrial function during the progression of type 2 diabetes mellitus with regard to mitochondrial respiration, protein expression, and reactive oxygen species production. In addition, this is the first measurement of rattin levels in the cerebral vasculature, which could potentially lead to novel treatment options.


Subject(s)
Cerebral Arteries/metabolism , Diabetes Mellitus, Type 2/metabolism , Energy Metabolism , Mitochondria/metabolism , Animals , Blood Glucose/metabolism , Cell Respiration , Cerebral Arteries/pathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/pathology , Disease Models, Animal , Male , Mitochondria/pathology , Proteins/metabolism , Rats, Zucker , Superoxides/metabolism , Time Factors
5.
J Cereb Blood Flow Metab ; 39(6): 1056-1068, 2019 06.
Article in English | MEDLINE | ID: mdl-29215305

ABSTRACT

The underlying factors promoting increased mitochondrial proteins, mtDNA, and dilation to mitochondrial-specific agents in male rats following tMCAO are not fully elucidated. Our goal was to determine the morphological and functional effects of ischemia/reperfusion (I/R) on mitochondria using electron microscopy, Western blot, mitochondrial oxygen consumption rate (OCR), and Ca2+ sparks activity measurements in middle cerebral arteries (MCAs) from male Sprague Dawley rats (Naïve, tMCAO, Sham). We found a greatly increased OCR in ipsilateral MCAs (IPSI) compared with contralateral (CONTRA), Sham, and Naïve MCAs. Consistent with our earlier findings, the expression of Mitofusin-2 and OPA-1 was significantly decreased in IPSI arteries compared with Sham and Naïve. Mitochondrial morphology was disrupted in vascular smooth muscle, but morphology with normal and perhaps greater numbers of mitochondria were observed in IPSI compared with CONTRA MCAs. Consistently, there were significantly fewer baseline Ca2+ events in IPSI MCAs compared with CONTRA, Sham, and Naïve. Mitochondrial depolarization significantly increased Ca2+ sparks activity in the IPSI, Sham, Naïve, but not in the CONTRA group. Our data indicate that altered mitochondrial structure and function occur in MCAs exposed to I/R and that these changes impact not only OCR but Ca2+ sparks activity in both IPSI and CONTRA MCAs.


Subject(s)
Cerebral Arteries/physiology , Energy Metabolism , Mitochondria/metabolism , Reperfusion Injury/metabolism , Animals , Calcium/metabolism , Male , Middle Cerebral Artery/pathology , Mitochondria/ultrastructure , Muscle, Smooth, Vascular/ultrastructure , Oxygen Consumption , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathology
6.
Geroscience ; 40(4): 365-375, 2018 08.
Article in English | MEDLINE | ID: mdl-30074132

ABSTRACT

Cerebral blood flow (CBF) is uniquely regulated by the anatomical design of the cerebral vasculature as well as through neurovascular coupling. The process of directing the CBF to meet the energy demands of neuronal activity is referred to as neurovascular coupling. Microvasculature in the brain constitutes the critical component of the neurovascular coupling. Mitochondria provide the majority of ATP to meet the high-energy demand of the brain. Impairment of mitochondrial function plays a central role in several age-related diseases such as hypertension, ischemic brain injury, Alzheimer's disease, and Parkinson disease. Interestingly, microvessels and small arteries of the brain have been the focus of the studies implicating the vascular mechanisms in several age-related neurological diseases. However, the role of microvascular mitochondrial dysfunction in age-related diseases remains unexplored. To date, high-throughput assay for measuring mitochondrial respiration in microvessels is lacking. The current study presents a novel method to measure mitochondrial respiratory parameters in freshly isolated microvessels from mouse brain ex vivo using Seahorse XFe24 Analyzer. We validated the method by demonstrating impairments of mitochondrial respiration in cerebral microvessels isolated from old mice compared to the young mice. Thus, application of mitochondrial respiration studies in microvessels will help identify novel vascular mechanisms underlying a variety of age-related neurological diseases.


Subject(s)
Aging/metabolism , Cerebrovascular Circulation/physiology , High-Throughput Screening Assays/methods , Microvessels/metabolism , Oxygen Consumption/physiology , Adenosine Triphosphate/metabolism , Animals , Cell Respiration , Cerebral Arteries/metabolism , In Vitro Techniques , Male , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Models, Animal , Reference Values , Sensitivity and Specificity
7.
J Vasc Res ; 54(1): 1-12, 2017.
Article in English | MEDLINE | ID: mdl-28095372

ABSTRACT

Mitochondrial dysfunction has been suggested as a potential underlying cause of pathological conditions associated with type 2 diabetes (T2DM). We have previously shown that mitochondrial respiration and mitochondrial protein levels were similar in the large cerebral arteries of insulin-resistant Zucker obese rats and their lean controls. In this study, we extend our investigations into the mitochondrial dynamics of the cerebral vasculature of 14-week-old Zucker diabetic fatty obese (ZDFO) rats with early T2DM. Body weight and blood glucose levels were significantly higher in the ZDFO group, and basal mitochondrial respiration and proton leak were significantly decreased in the large cerebral arteries of the ZDFO rats compared with the lean controls (ZDFL). The expression of the mitochondrial proteins total manganese superoxide dismutase (MnSOD) and voltage-dependent anion channel (VDAC) were significantly lower in the cerebral microvessels, and acetylated MnSOD levels were significantly reduced in the large arteries of the ZDFO group. Additionally, superoxide production was significantly increased in the microvessels of the ZDFO group. Despite evidence of increased oxidative stress in ZDFO, exogenous SOD was not able to restore mitochondrial respiration in the ZDFO rats. Our results show, for the first time, that mitochondrial respiration and protein levels are compromised during the early stages of T2DM.


Subject(s)
Cerebral Arteries/metabolism , Cerebrovascular Disorders/etiology , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/etiology , Mitochondria/metabolism , Mitochondrial Dynamics , Acetylation , Animals , Blood Glucose/metabolism , Body Weight , Cell Respiration , Cerebral Arteries/drug effects , Cerebrovascular Disorders/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Angiopathies/metabolism , Disease Models, Animal , Free Radical Scavengers/pharmacology , Male , Microvessels/metabolism , Mitochondria/drug effects , Mitochondrial Dynamics/drug effects , Oxidative Stress , Rats, Zucker , Superoxide Dismutase/metabolism , Superoxides/metabolism , Time Factors , Voltage-Dependent Anion Channels/metabolism
8.
Am J Physiol Heart Circ Physiol ; 310(7): H830-8, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26873973

ABSTRACT

Little is known about mitochondrial functioning in the cerebral vasculature during insulin resistance (IR). We examined mitochondrial respiration in isolated cerebral arteries of male Zucker obese (ZO) rats and phenotypically normal Zucker lean (ZL) rats using the Seahorse XFe24 analyzer. We investigated mitochondrial morphology in cerebral blood vessels as well as mitochondrial and nonmitochondrial protein expression levels in cerebral arteries and microvessels. We also measured reactive oxygen species (ROS) levels in cerebral microvessels. Under basal conditions, the mitochondrial respiration components (nonmitochondrial respiration, basal respiration, ATP production, proton leak, and spare respiratory capacity) showed similar levels among the ZL and ZO groups with the exception of maximal respiration, which was higher in the ZO group. We examined the role of nitric oxide by measuring mitochondrial respiration following inhibition of nitric oxide synthase with N(ω)-nitro-l-arginine methyl ester (l-NAME) and mitochondrial activation after administration of diazoxide (DZ). Both ZL and ZO groups showed similar responses to these stimuli with minor variations.l-NAME significantly increased the proton leak, and DZ decreased nonmitochondrial respiration in the ZL group. Other components were not affected. Mitochondrial morphology and distribution within vascular smooth muscle and endothelium as well as mitochondrial protein levels were similar in the arteries and microvessels of both groups. Endothelial nitric oxide synthase (eNOS) and ROS levels were increased in cerebral microvessels of the ZO. Our study suggests that mitochondrial function is not significantly altered in the cerebral vasculature of young ZO rats, but increased ROS production might be due to increased eNOS in the cerebral microcirculation during IR.


Subject(s)
Cerebral Arteries/metabolism , Insulin Resistance , Microvessels/metabolism , Mitochondria/metabolism , Obesity/metabolism , Adenosine Triphosphate/metabolism , Animals , Cell Respiration , Endothelium, Vascular/metabolism , Male , Muscle, Smooth, Vascular/metabolism , Nitric Oxide Synthase Type III/antagonists & inhibitors , Nitric Oxide Synthase Type III/metabolism , Rats , Rats, Zucker , Reactive Oxygen Species/metabolism
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