Hayrunnisa Bolay - Academia.edu (original) (raw)
Papers by Hayrunnisa Bolay
Journal of Clinical Medicine
Background: Irritable bowel syndrome (IBS) is an under-diagnosed common health problem that impai... more Background: Irritable bowel syndrome (IBS) is an under-diagnosed common health problem that impairs quality of life. Migraine and IBS are comorbid disorders that are triggered by foods. We aim to investigate IBS frequency in medication overuse headache (MOH) patients and identify food triggers and food avoidance behavior. Methods: Participants who completed the cross-sectional, observational and online survey were included (n = 1118). Demographic data, comorbid disorders, medications used, presence of headache, the diagnostic features of headache and IBS, migraine related subjective cognitive symptoms scale (MigSCog), consumption behavior of patients regarding 125 food/food additives and food triggers were asked about in the questionnaire. Results: Migraine and MOH diagnoses were made in 88% and 30.7% of the participants, respectively. Non-steroidal anti-inflammatory drugs (NSAIDs) were the main overused drug (89%) in MOH patients. IBS symptoms were present in 35.8% of non-headache ...
Headache, Jan 27, 2023
Background and ObjectiveDysfunctional sensory processing is described in migraine. This study aim... more Background and ObjectiveDysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test.MethodsA total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light‐emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack.ResultsThe VTDT of each visual field in both attack (mean [SD] 102.3 [38.4] ms for the right visual field and 106.3 [52.2] ms for the left) and the interictal periods (mean [SD] 75.2 [27.9] ms for the right and 78.2 [27.9] ms for the left) were significantly higher than in the control group (mean [SD] 45.3 [9.9] ms for the right and 48.2 [11.9] ms for the left) (p < 0.001, p < 0.001, p = 0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8 [53.8] vs. 78 [19.6] ms, p = 0.025) and the contralateral threshold during the attack (mean [SD] 143.8 [53.8] vs. 71.9 [14.1] ms, p = 0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r = 0.894, p < 0.001) and frequency of the attacks (r = 0.696, p = 0.004), but not correlated with photophobia.ConclusionThe VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus.
Headache, Oct 21, 2020
Multimodal sensorial disruption typically accompanies migraine attacks and patients may experienc... more Multimodal sensorial disruption typically accompanies migraine attacks and patients may experience sensory stimuli such as light, sound, touch, and odors as unpleasant or even painful. Sensorimotor integration is an anatomical and functional process with motor orders and sensory feedback and also with cognitive events. Different sensory modalities need to be identified and translated into coding to plan an action where the high-order thalamus mediates synchronization of cortical oscillations. Preclinical research revealed the critical involvement of thalamic reticular nucleus and clinical studies in migraine patients disclosed reduced sensory gating, abnormal early high-frequency oscillations, impaired somatosensory temporal discrimination thresholds, and disrupted integrity of sensorial input with motor output in sensorimotor cortex indicating the dysfunctional inhibitor circuit. Current evidences suggest that central sensory processing and sensorimotor integration are affected in migraine patients probably reflecting an increased excitability state toward the headache attacks.
Turkish Journal of Biology, Feb 9, 2021
Introduction Accumulating cellular iron was found to differ in chronic and episodic migraine pati... more Introduction Accumulating cellular iron was found to differ in chronic and episodic migraine patients and was associated with the duration of pain; however, no iron accumulation was shown in headache triggered by medication or stress (Tepper et al., 2012). Free radical damage associated with hyperemia that develops during recurrent attacks was also found related with iron accumulation in brain areas activated during migraine (Goadsby 2012). Cellular accumulation of iron disrupted normal antinociceptive function by various ways and contributed to pain formation (Kruit et al., 2009). Glial cells, which control inflammation in homeostatic as well as neurodegenerative processes, are the key players maintaining iron in central nervous system (CNS). Microglia prevent excessive accumulation of iron by storing it in different forms (Kaur and Ling, 2009), while astrocytes regulate iron metabolism via molecules involved in iron transport and storage (Jeong and David, 2003). Matrix metalloproteinase (MMP)-9 produced by glial cells mediates the pain pathways by recruiting activated immune cells to the scene of inflammation and increasing blood-brain barrier (BBB) permeability by disrupting the endothelial cell basal laminae (Gursoy-Ozdemir et al., 2004, Gawlak et al, 2009). Studies conducted in recent years reveal that glial cells contribute to migraine pathogenesis by changing the BBB permeability (Ricci et al., 2009). A relationship between MMP-9 and cellular iron homeostasis in glial cells in migraine pathophysiology has not yet been disclosed. Owing to its ability to gain and lose electrons easily, iron is considered an important part of metabolism. In addition to BBB, multiple control systems within the brain tissue regulate cellular iron at sufficient levels to maintain the normal functions of nervous system (Mills et al., 2010). Proteins that take iron into the cell are called influx Abstract: A well-balanced intracellular iron trafficking in glial cells plays a role in homeostatic processes. Elevated intracellular iron triggers oxidative stress and cell damage in many neurological disorders, including migraine. This study aimed to investigate the effects of glyceryl trinitrate (GTN), on cellular iron homeostasis, matrixmetalloproteinase (MMP)-9, and calcitonin gene related peptide (CGRP) receptor (CRLR/CGRPR1) production in microglia, astrocyte, and meningeal cell cultures. Primary glial and meningeal cells in culture were exposed to GTN for 24 h. Messenger RNA expression was assessed using qPCR. Iron accumulation was visualized via modified Perl's histochemistry. MMP-9 levels in cell culture supernatants were measured using ELISA. Ferritin and CRLR/CGRPR1 proteins were visualized via immunofluorescence staining. Nitric oxide production increased significantly with GTN in meningeal and glial cells. GTN significantly increased the expression of the storage protein ferritin for all three cell types, but ferritin-L for meningeal cells and microglia. Iron trafficking associated with the efflux protein ferroportin and influx protein divalent metal transporter (DMT)1 was affected differently in all three cell types. MMP-9 expression was increased in astrocytes. GTN stimulation increased both CRLR/ CGRPR1 expression, and immunostaining was apparent in microglia and meningeal cells. This study showed for the first time that GTN modulates intracellular iron trafficking regulated by storage and transport proteins expressed in meningeal cells and glia. CRLR/ CGRPR1 expression might be related to altered iron homeostasis and they both may stimulate nociceptive pathways activated in migraine. These molecules expressed differently in glial and meningeal cells in response to GTN may bring not only new targets forward in treatment but also prevention in migraine.
Frontiers in Neurology
ObjectiveTo investigate the possible subgroups of patients with Cluster Headache (CH) by using K-... more ObjectiveTo investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis.MethodsA total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences.ResultsCluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smokin...
Turkish Journal of Medical Sciences
Neonatal brain injury is a significant reason of neurodevelopmental abnormalities and long-term n... more Neonatal brain injury is a significant reason of neurodevelopmental abnormalities and long-term neurological impairments. Hypoxic-ischemic encephalopathy and preterm brain injury, including intraventricular hemorrhage are the most common grounds of brain injury for full-term and preterm neonates. The prevalence of hypoxic ischemic encephalopathy varies globally, ranging from 1 to 3.5/1000 live births in high-resource countries and 26/1000 in low-resource countries. Preterm birth's global incidence is 15 million, a significant reason for infant mortality and morbidity, permanent neurologic problems, and the associated social and economic burden. The widespread neurodevelopmental effects of neonatal brain injury could have an unfavorable impact on a variety of aspects of cognitive, linguistic, behavioral, sensory, and motor functions. Brain injury occurs via various mechanisms, including energy deprivation, excitatory amino acids, mitochondrial dysfunction, reactive oxygen species, and inflammation giving rise to different forms of cell death. The contribution of microglial activity in neonatal brain injury has widely been underlined by focusing on cell death mechanisms since the neuronal death pathways during their development are distinct from those in the adult brain. Iron accumulation and lipid peroxidation cause a relatively novel type of regulated cell death called ferroptosis. Neonates generally have biochemical iron inequalities, and their antioxidant potential is highly restricted, implying that ferroptosis may be significant in pathologic conditions. Moreover, inhaled nitric oxide therapy in infants may lead to microglial inflammation via ferroptosis and neuronal injury in the developing brain. This review article aims to summarize the studies that investigated the association between neonatal brain injury and iron metabolism, with a particular emphasis on the microglial activity and its application to the inhibition of neonatal brain injury.
Background: Migraine (MIG) is a common cause of headache and a leading cause of morbidity in Turk... more Background: Migraine (MIG) is a common cause of headache and a leading cause of morbidity in Turkey but comprehensive and comparative data evaluating its burden are scarce. The study aimed to describe clinical characteristics and management of MIG and compare MIG with tension type headache (TTH) regarding the burden of disease and healthcare resource utilization. Methods: A total of 1368 patients (aged 18-65 years) with MIG or TTH were surveyed regarding patients’ sociodemographics, headache characteristics, clinical management, burden of disease, quality of life and healthcare resource utilization within the previous 12 months. Data from 1053 patients with definite MIG (dMIG) (n: 924; 87.7%) or definite TTH (dTTH) (n: 129; 12.3%) criteria were analyzed.Results: The frequency and duration of attacks, the number of monthly headache days and of days with analgesic consumption and the severity of headaches were higher in dMIG than in dTTH (p:0.005 for the frequency of attacks and p<...
International Headache Congress -- JUN 27-30, 2013 -- Boston, MAWOS: 000321333800048…Int Headache... more International Headache Congress -- JUN 27-30, 2013 -- Boston, MAWOS: 000321333800048…Int Headache Soc, Amer Headache So
Background: Our purpose was to investigate the demographics, diagnosis patterns, clinical charact... more Background: Our purpose was to investigate the demographics, diagnosis patterns, clinical characteristics, triggers, treatment experiences, and personal burden of patients with Cluster headache (CH) in Turkey, a country located between Europe and Asia.Methods: The study is a cross-sectional investigation based on data from eight headache centers in Turkey. All patients completed the semi-structured survey either face to face or by phone interview with a neurologist.Results: A total of 209 individuals with a mean age of 39.8 (11.3) completed the survey (176 males; 188 episodic, 21 chronic). The mean age at disease onset was 28.6 (10.2) years. The diagnostic delay was 4.9 years and misdiagnosis before CH was 57.9%. Of participants, 9.1% reported a positive family history for CH. Male patients with CH showed higher rates for being current smokers in comparison to females (59.7% vs. 24.2%; p<0.0001) and they also had significantly more past history of smoking at the time of first dia...
Archives of Neuropsychiatry, 2020
Introduction: Interventions performed in the early period of life are associated with cognitive a... more Introduction: Interventions performed in the early period of life are associated with cognitive and behavioral changes in adulthood. The effects of interventions such as exposure to an early stressful life event or environmental enrichment on cognitive and behavioral development are studied. The aim of this study is to develop a new intervention method, to investigate the effects of early interventions on social interaction, memory anxiety levels and NR2B levels in prefrontal and hippocampus in adulthood. The hypothesis of the study is that exposure to the ambivalent mother will affect the behavioral performance of rats at least as much as one hour apart from the mother in the adult period and cause changes in the prefrontal cortex and hippocampus in the NR2B levels. Method: In the study, the Wistar rats were divided into four groups as control group (12), group that remained 15 minutes apart from mother (Mild Stress) (12), group that remained 60 minutes apart from mother (Severe Stress) (14) and ambivalent mother group (13). In adulthood, the social interaction test, elevated plus maze and new object recognition test performances of rats were evaluated. ELISA method was used to evaluate the effect of interventions on the prefrontal cortex and hippocampus NMDA R2B levels. Results: The important findings of the study were that in the new object recognition test, separation from the mother did not affect the recognition memory regardless of gender, while the short-term recognition memory of the females of the ambivalent mothers' group was better than the females in the other groups and the long-term memory performance of the mild stress groups men was better than the man in the other groups. In addition, in the social interaction test, the males of the ambivalent group and the mild stress group showed more aggressive behavior. It was determined that the prefrontal cortex NR2B level was higher in the mild stress and ambivalent mother group compared to the severe stress group, and NR2B level was increased in all intervention groups compared to the control group. Conclusion: In contrast to the hypothesis, the results of this study support that the ambivalent mother's group rats are not more adversely affected than the severe group rats and that the model created may be an environmental enrichment model rather than an early stressful life event exposure.
European Neuropsychopharmacology, 2019
S273 tized animals although it did not reach to a significant level. Ani-AKH (p < 0.05) and Pht-H... more S273 tized animals although it did not reach to a significant level. Ani-AKH (p < 0.05) and Pht-HrTH (p < 0.05) significantly decreased weight gain in 3 weeks of administration compared to non-traumatized control group while Ani-AKH (p < 0.05) and Pht-HrTH (p < 0.001) significantly increased weight gain compared to traumatized control group in the PTSD study. In the ASR test, Ani-AKH (p < 0.01), Lia-AKH (p < 0.01) and Pht-HrTH (p < 0.05) significantly decreased average startle amplitude compared to non-traumatized control group. In conclusion, AKH/RPCH family peptides may demonstrate improved effects on animal behavior in PTSD model in rats although effects were varying depending on the test applied and type of insect hormone used. References
Objective: Medication overuse headache (MOH) is secondary headache that accompanies chronic migra... more Objective: Medication overuse headache (MOH) is secondary headache that accompanies chronic migraine and NSAIDs are the most frequently use analgesics in the word. NSAIDs are known to induce leaky gut and we aimed to investigate whether NSAID induced MOH is associated with altered circulating LBP levels and inflammatory molecules. Materials and Methods: Piroxicam (10 mg /kg, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain was tested by evaluating periorbital von Frey thresholds, grooming, freezing and headshake behavior. Serum samples and brain tissues were collected to measure circulating LPS binding protein (LBP), tight junction protein occludin, adherence junction protein vascular endothelial (VE)-cadherin, CGRP, IL-6, levels. HMGB1 and IL-17 were determined in brain tissues. Results: Chronic piroxicam exposure resulted in decreased periorbital mechanical thresholds, increased grooming, freezing and headshake behavior compared to vehicle administration....
The Journal of Headache and Pain
Background Migraine headache attacks and accompanying sensory augmentation can be induced by seve... more Background Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura. Methods Wistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark–light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood–b...
Headache Disorders in Pandemic Conditions
Türk Nöroşirürji Dergsi, 2018
Expert Review of Neurotherapeutics, 2021
ABSTRACT Introduction: Experimental animal studies have revealed mechanisms that link cortical sp... more ABSTRACT Introduction: Experimental animal studies have revealed mechanisms that link cortical spreading depression (CSD) to the trigeminal activation mediating lateralized headache. However, conventional CSD as seen in lissencephalic brain is insufficient to explain some clinical features of aura and migraine headache. Areas covered: The importance of CSD in headache development including dysfunction of the thalamocortical network, neuroinflammation, calcitonin gene-related peptide, transgenic models, and the role of CSD in migraine triggers, treatment options, neuromodulation, and future directions are reviewed. Expert opinion: The conventional understanding of CSD marching across the hemisphere is invalid in gyrencephalic brains. Thalamocortical dysfunction and interruption of functional cortical network systems by CSD may provide alternative explanations for clinical manifestations of migraine phases including aura. Not all drugs showing CSD blocking properties in lissencephalic brains have efficacy in migraine headache and monoclonal antibodies against CGRP ligand/receptors which are effective in migraine treatment, have no impact on aura in humans or CSD properties in rodents. Functional networks and molecular mechanisms mediating and amplifying the effects of limited CSD in migraine brain remain to be investigated to define new targets.
Headache: The Journal of Head and Face Pain, 2020
Headache was reported in up to one‐third of the hospitalized patients; yet, the clinical characte... more Headache was reported in up to one‐third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID‐19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID‐19 illness. Headache features in 13 PCR‐confirmed COVID‐19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID‐19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine‐like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patie...
Journal of Clinical Medicine
Background: Irritable bowel syndrome (IBS) is an under-diagnosed common health problem that impai... more Background: Irritable bowel syndrome (IBS) is an under-diagnosed common health problem that impairs quality of life. Migraine and IBS are comorbid disorders that are triggered by foods. We aim to investigate IBS frequency in medication overuse headache (MOH) patients and identify food triggers and food avoidance behavior. Methods: Participants who completed the cross-sectional, observational and online survey were included (n = 1118). Demographic data, comorbid disorders, medications used, presence of headache, the diagnostic features of headache and IBS, migraine related subjective cognitive symptoms scale (MigSCog), consumption behavior of patients regarding 125 food/food additives and food triggers were asked about in the questionnaire. Results: Migraine and MOH diagnoses were made in 88% and 30.7% of the participants, respectively. Non-steroidal anti-inflammatory drugs (NSAIDs) were the main overused drug (89%) in MOH patients. IBS symptoms were present in 35.8% of non-headache ...
Headache, Jan 27, 2023
Background and ObjectiveDysfunctional sensory processing is described in migraine. This study aim... more Background and ObjectiveDysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test.MethodsA total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light‐emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack.ResultsThe VTDT of each visual field in both attack (mean [SD] 102.3 [38.4] ms for the right visual field and 106.3 [52.2] ms for the left) and the interictal periods (mean [SD] 75.2 [27.9] ms for the right and 78.2 [27.9] ms for the left) were significantly higher than in the control group (mean [SD] 45.3 [9.9] ms for the right and 48.2 [11.9] ms for the left) (p < 0.001, p < 0.001, p = 0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8 [53.8] vs. 78 [19.6] ms, p = 0.025) and the contralateral threshold during the attack (mean [SD] 143.8 [53.8] vs. 71.9 [14.1] ms, p = 0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r = 0.894, p < 0.001) and frequency of the attacks (r = 0.696, p = 0.004), but not correlated with photophobia.ConclusionThe VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus.
Headache, Oct 21, 2020
Multimodal sensorial disruption typically accompanies migraine attacks and patients may experienc... more Multimodal sensorial disruption typically accompanies migraine attacks and patients may experience sensory stimuli such as light, sound, touch, and odors as unpleasant or even painful. Sensorimotor integration is an anatomical and functional process with motor orders and sensory feedback and also with cognitive events. Different sensory modalities need to be identified and translated into coding to plan an action where the high-order thalamus mediates synchronization of cortical oscillations. Preclinical research revealed the critical involvement of thalamic reticular nucleus and clinical studies in migraine patients disclosed reduced sensory gating, abnormal early high-frequency oscillations, impaired somatosensory temporal discrimination thresholds, and disrupted integrity of sensorial input with motor output in sensorimotor cortex indicating the dysfunctional inhibitor circuit. Current evidences suggest that central sensory processing and sensorimotor integration are affected in migraine patients probably reflecting an increased excitability state toward the headache attacks.
Turkish Journal of Biology, Feb 9, 2021
Introduction Accumulating cellular iron was found to differ in chronic and episodic migraine pati... more Introduction Accumulating cellular iron was found to differ in chronic and episodic migraine patients and was associated with the duration of pain; however, no iron accumulation was shown in headache triggered by medication or stress (Tepper et al., 2012). Free radical damage associated with hyperemia that develops during recurrent attacks was also found related with iron accumulation in brain areas activated during migraine (Goadsby 2012). Cellular accumulation of iron disrupted normal antinociceptive function by various ways and contributed to pain formation (Kruit et al., 2009). Glial cells, which control inflammation in homeostatic as well as neurodegenerative processes, are the key players maintaining iron in central nervous system (CNS). Microglia prevent excessive accumulation of iron by storing it in different forms (Kaur and Ling, 2009), while astrocytes regulate iron metabolism via molecules involved in iron transport and storage (Jeong and David, 2003). Matrix metalloproteinase (MMP)-9 produced by glial cells mediates the pain pathways by recruiting activated immune cells to the scene of inflammation and increasing blood-brain barrier (BBB) permeability by disrupting the endothelial cell basal laminae (Gursoy-Ozdemir et al., 2004, Gawlak et al, 2009). Studies conducted in recent years reveal that glial cells contribute to migraine pathogenesis by changing the BBB permeability (Ricci et al., 2009). A relationship between MMP-9 and cellular iron homeostasis in glial cells in migraine pathophysiology has not yet been disclosed. Owing to its ability to gain and lose electrons easily, iron is considered an important part of metabolism. In addition to BBB, multiple control systems within the brain tissue regulate cellular iron at sufficient levels to maintain the normal functions of nervous system (Mills et al., 2010). Proteins that take iron into the cell are called influx Abstract: A well-balanced intracellular iron trafficking in glial cells plays a role in homeostatic processes. Elevated intracellular iron triggers oxidative stress and cell damage in many neurological disorders, including migraine. This study aimed to investigate the effects of glyceryl trinitrate (GTN), on cellular iron homeostasis, matrixmetalloproteinase (MMP)-9, and calcitonin gene related peptide (CGRP) receptor (CRLR/CGRPR1) production in microglia, astrocyte, and meningeal cell cultures. Primary glial and meningeal cells in culture were exposed to GTN for 24 h. Messenger RNA expression was assessed using qPCR. Iron accumulation was visualized via modified Perl's histochemistry. MMP-9 levels in cell culture supernatants were measured using ELISA. Ferritin and CRLR/CGRPR1 proteins were visualized via immunofluorescence staining. Nitric oxide production increased significantly with GTN in meningeal and glial cells. GTN significantly increased the expression of the storage protein ferritin for all three cell types, but ferritin-L for meningeal cells and microglia. Iron trafficking associated with the efflux protein ferroportin and influx protein divalent metal transporter (DMT)1 was affected differently in all three cell types. MMP-9 expression was increased in astrocytes. GTN stimulation increased both CRLR/ CGRPR1 expression, and immunostaining was apparent in microglia and meningeal cells. This study showed for the first time that GTN modulates intracellular iron trafficking regulated by storage and transport proteins expressed in meningeal cells and glia. CRLR/ CGRPR1 expression might be related to altered iron homeostasis and they both may stimulate nociceptive pathways activated in migraine. These molecules expressed differently in glial and meningeal cells in response to GTN may bring not only new targets forward in treatment but also prevention in migraine.
Frontiers in Neurology
ObjectiveTo investigate the possible subgroups of patients with Cluster Headache (CH) by using K-... more ObjectiveTo investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis.MethodsA total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences.ResultsCluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smokin...
Turkish Journal of Medical Sciences
Neonatal brain injury is a significant reason of neurodevelopmental abnormalities and long-term n... more Neonatal brain injury is a significant reason of neurodevelopmental abnormalities and long-term neurological impairments. Hypoxic-ischemic encephalopathy and preterm brain injury, including intraventricular hemorrhage are the most common grounds of brain injury for full-term and preterm neonates. The prevalence of hypoxic ischemic encephalopathy varies globally, ranging from 1 to 3.5/1000 live births in high-resource countries and 26/1000 in low-resource countries. Preterm birth's global incidence is 15 million, a significant reason for infant mortality and morbidity, permanent neurologic problems, and the associated social and economic burden. The widespread neurodevelopmental effects of neonatal brain injury could have an unfavorable impact on a variety of aspects of cognitive, linguistic, behavioral, sensory, and motor functions. Brain injury occurs via various mechanisms, including energy deprivation, excitatory amino acids, mitochondrial dysfunction, reactive oxygen species, and inflammation giving rise to different forms of cell death. The contribution of microglial activity in neonatal brain injury has widely been underlined by focusing on cell death mechanisms since the neuronal death pathways during their development are distinct from those in the adult brain. Iron accumulation and lipid peroxidation cause a relatively novel type of regulated cell death called ferroptosis. Neonates generally have biochemical iron inequalities, and their antioxidant potential is highly restricted, implying that ferroptosis may be significant in pathologic conditions. Moreover, inhaled nitric oxide therapy in infants may lead to microglial inflammation via ferroptosis and neuronal injury in the developing brain. This review article aims to summarize the studies that investigated the association between neonatal brain injury and iron metabolism, with a particular emphasis on the microglial activity and its application to the inhibition of neonatal brain injury.
Background: Migraine (MIG) is a common cause of headache and a leading cause of morbidity in Turk... more Background: Migraine (MIG) is a common cause of headache and a leading cause of morbidity in Turkey but comprehensive and comparative data evaluating its burden are scarce. The study aimed to describe clinical characteristics and management of MIG and compare MIG with tension type headache (TTH) regarding the burden of disease and healthcare resource utilization. Methods: A total of 1368 patients (aged 18-65 years) with MIG or TTH were surveyed regarding patients’ sociodemographics, headache characteristics, clinical management, burden of disease, quality of life and healthcare resource utilization within the previous 12 months. Data from 1053 patients with definite MIG (dMIG) (n: 924; 87.7%) or definite TTH (dTTH) (n: 129; 12.3%) criteria were analyzed.Results: The frequency and duration of attacks, the number of monthly headache days and of days with analgesic consumption and the severity of headaches were higher in dMIG than in dTTH (p:0.005 for the frequency of attacks and p<...
International Headache Congress -- JUN 27-30, 2013 -- Boston, MAWOS: 000321333800048…Int Headache... more International Headache Congress -- JUN 27-30, 2013 -- Boston, MAWOS: 000321333800048…Int Headache Soc, Amer Headache So
Background: Our purpose was to investigate the demographics, diagnosis patterns, clinical charact... more Background: Our purpose was to investigate the demographics, diagnosis patterns, clinical characteristics, triggers, treatment experiences, and personal burden of patients with Cluster headache (CH) in Turkey, a country located between Europe and Asia.Methods: The study is a cross-sectional investigation based on data from eight headache centers in Turkey. All patients completed the semi-structured survey either face to face or by phone interview with a neurologist.Results: A total of 209 individuals with a mean age of 39.8 (11.3) completed the survey (176 males; 188 episodic, 21 chronic). The mean age at disease onset was 28.6 (10.2) years. The diagnostic delay was 4.9 years and misdiagnosis before CH was 57.9%. Of participants, 9.1% reported a positive family history for CH. Male patients with CH showed higher rates for being current smokers in comparison to females (59.7% vs. 24.2%; p<0.0001) and they also had significantly more past history of smoking at the time of first dia...
Archives of Neuropsychiatry, 2020
Introduction: Interventions performed in the early period of life are associated with cognitive a... more Introduction: Interventions performed in the early period of life are associated with cognitive and behavioral changes in adulthood. The effects of interventions such as exposure to an early stressful life event or environmental enrichment on cognitive and behavioral development are studied. The aim of this study is to develop a new intervention method, to investigate the effects of early interventions on social interaction, memory anxiety levels and NR2B levels in prefrontal and hippocampus in adulthood. The hypothesis of the study is that exposure to the ambivalent mother will affect the behavioral performance of rats at least as much as one hour apart from the mother in the adult period and cause changes in the prefrontal cortex and hippocampus in the NR2B levels. Method: In the study, the Wistar rats were divided into four groups as control group (12), group that remained 15 minutes apart from mother (Mild Stress) (12), group that remained 60 minutes apart from mother (Severe Stress) (14) and ambivalent mother group (13). In adulthood, the social interaction test, elevated plus maze and new object recognition test performances of rats were evaluated. ELISA method was used to evaluate the effect of interventions on the prefrontal cortex and hippocampus NMDA R2B levels. Results: The important findings of the study were that in the new object recognition test, separation from the mother did not affect the recognition memory regardless of gender, while the short-term recognition memory of the females of the ambivalent mothers' group was better than the females in the other groups and the long-term memory performance of the mild stress groups men was better than the man in the other groups. In addition, in the social interaction test, the males of the ambivalent group and the mild stress group showed more aggressive behavior. It was determined that the prefrontal cortex NR2B level was higher in the mild stress and ambivalent mother group compared to the severe stress group, and NR2B level was increased in all intervention groups compared to the control group. Conclusion: In contrast to the hypothesis, the results of this study support that the ambivalent mother's group rats are not more adversely affected than the severe group rats and that the model created may be an environmental enrichment model rather than an early stressful life event exposure.
European Neuropsychopharmacology, 2019
S273 tized animals although it did not reach to a significant level. Ani-AKH (p < 0.05) and Pht-H... more S273 tized animals although it did not reach to a significant level. Ani-AKH (p < 0.05) and Pht-HrTH (p < 0.05) significantly decreased weight gain in 3 weeks of administration compared to non-traumatized control group while Ani-AKH (p < 0.05) and Pht-HrTH (p < 0.001) significantly increased weight gain compared to traumatized control group in the PTSD study. In the ASR test, Ani-AKH (p < 0.01), Lia-AKH (p < 0.01) and Pht-HrTH (p < 0.05) significantly decreased average startle amplitude compared to non-traumatized control group. In conclusion, AKH/RPCH family peptides may demonstrate improved effects on animal behavior in PTSD model in rats although effects were varying depending on the test applied and type of insect hormone used. References
Objective: Medication overuse headache (MOH) is secondary headache that accompanies chronic migra... more Objective: Medication overuse headache (MOH) is secondary headache that accompanies chronic migraine and NSAIDs are the most frequently use analgesics in the word. NSAIDs are known to induce leaky gut and we aimed to investigate whether NSAID induced MOH is associated with altered circulating LBP levels and inflammatory molecules. Materials and Methods: Piroxicam (10 mg /kg, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain was tested by evaluating periorbital von Frey thresholds, grooming, freezing and headshake behavior. Serum samples and brain tissues were collected to measure circulating LPS binding protein (LBP), tight junction protein occludin, adherence junction protein vascular endothelial (VE)-cadherin, CGRP, IL-6, levels. HMGB1 and IL-17 were determined in brain tissues. Results: Chronic piroxicam exposure resulted in decreased periorbital mechanical thresholds, increased grooming, freezing and headshake behavior compared to vehicle administration....
The Journal of Headache and Pain
Background Migraine headache attacks and accompanying sensory augmentation can be induced by seve... more Background Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura. Methods Wistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark–light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood–b...
Headache Disorders in Pandemic Conditions
Türk Nöroşirürji Dergsi, 2018
Expert Review of Neurotherapeutics, 2021
ABSTRACT Introduction: Experimental animal studies have revealed mechanisms that link cortical sp... more ABSTRACT Introduction: Experimental animal studies have revealed mechanisms that link cortical spreading depression (CSD) to the trigeminal activation mediating lateralized headache. However, conventional CSD as seen in lissencephalic brain is insufficient to explain some clinical features of aura and migraine headache. Areas covered: The importance of CSD in headache development including dysfunction of the thalamocortical network, neuroinflammation, calcitonin gene-related peptide, transgenic models, and the role of CSD in migraine triggers, treatment options, neuromodulation, and future directions are reviewed. Expert opinion: The conventional understanding of CSD marching across the hemisphere is invalid in gyrencephalic brains. Thalamocortical dysfunction and interruption of functional cortical network systems by CSD may provide alternative explanations for clinical manifestations of migraine phases including aura. Not all drugs showing CSD blocking properties in lissencephalic brains have efficacy in migraine headache and monoclonal antibodies against CGRP ligand/receptors which are effective in migraine treatment, have no impact on aura in humans or CSD properties in rodents. Functional networks and molecular mechanisms mediating and amplifying the effects of limited CSD in migraine brain remain to be investigated to define new targets.
Headache: The Journal of Head and Face Pain, 2020
Headache was reported in up to one‐third of the hospitalized patients; yet, the clinical characte... more Headache was reported in up to one‐third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID‐19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID‐19 illness. Headache features in 13 PCR‐confirmed COVID‐19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID‐19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine‐like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patie...