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Featured researches published by Nefize Turan.


Translational Stroke Research | 2016

Sex Differences in the Formation of Intracranial Aneurysms and Incidence and Outcome of Subarachnoid Hemorrhage: Review of Experimental and Human Studies.

Nefize Turan; Robert Allen-James Heider; Dobromira Zaharieva; Faiz U. Ahmad; Daniel L. Barrow; Gustavo Pradilla

Intracranial aneurysms are defined as pathological dilatations of cerebral arteries and rupture of intracranial aneurysms leads to subarachnoid hemorrhage (SAH). The goal of this review was to outline the sex differences in the formation and progression of intracranial aneurysms as well as sex-related differences in incidence and outcome of SAH. The literature review was performed using PubMed with a combination of these search terms: “subarachnoid hemorrhage,” “incidence,” “outcome,” “sex,” “gender,” “male,” “female,” “experimental,” “mice,” and “rats.” Studies written in English were used. Female sex is thought to be a risk factor for aneurysm formation, especially in postmenopausal age populations, suggesting the potential protective involvement of sex steroids. Female sex is also considered a risk factor for SAH occurrence. Although incidence and mortality are confirmed to be higher in females in most studies, they elucidated no clear differences in the functional outcome among SAH survivors. The effect of gender on the pathophysiology of SAH is not very well understood; nevertheless, the majority of pre-clinical studies suggest a beneficial effect of sex steroids in experimental SAH. Moreover, conflicting results exist on the role and effect of hormone replacement therapies and oral contraceptive pills on the incidence and outcome of human SAH. Sex differences exist in the formation of aneurysms as well as the incidence and mortality of SAH. Potential therapeutic effects of sex steroids have been replicated in many animal studies, but their potential use in the treatment of acute SAH in human populations needs more future study.


Journal of Cerebral Blood Flow and Metabolism | 2017

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents:

Nefize Turan; Brandon A. Miller; Robert Allen-James Heider; Maheen Nadeem; Iqbal Sayeed; Donald G. Stein; Gustavo Pradilla

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.


Journal of Neurosurgery | 2017

External ventricular drain practice variations: results from a nationwide survey

Griffin R. Baum; Kristopher G. Hooten; Dennis T. Lockney; Kyle M. Fargen; Nefize Turan; Gustavo Pradilla; Gregory J. A. Murad; Robert E. Harbaugh; Michael J. Glantz

OBJECTIVE While guidelines exist for many neurosurgical procedures, external ventricular drain (EVD) insertion has yet to be standardized. The goal of this study was to survey the neurosurgical community and determine the most frequent EVD insertion practices. The hypothesis was that there would be no standard practices identified for EVD insertion or methods to avoid EVD-associated infections. METHODS The American Association of Neurological Surgeons membership database was queried for all eligible neurosurgeons. A 16-question, multiple-choice format survey was created and sent to 7217 recipients. The responses were collected electronically, and the descriptive results were tabulated. Data were analyzed using the chi-square test. RESULTS In total, 1143 respondents (15.8%) completed the survey, and 705 respondents (61.6%) reported tracking EVD infections at their institution. The most common self-reported infection rate ranged from 1% to 3% (56.1% of participants), and 19.7% of respondents reported a 0% infection rate. In total, 451 respondents (42.7%) indicated that their institution utilizes a formal protocol for EVD placement. If a respondents institution had a protocol, only 258 respondents (36.1%) always complied with the protocol. Protocol utilization for EVD insertion was significantly more frequent among residents, in academic/hybrid centers, in ICU settings, and if the institution tracked EVD-associated infection rates (p < 0.05). A self-reported 0% infection rate was significantly more commonly associated with a higher level of training (e.g., attending physicians), private center settings, a clinician performing 6 to 10 EVD insertions within the previous 12 months, and prophylactic continuous antibiotic utilization (p < 0.05). CONCLUSIONS This survey demonstrated heterogeneity in the practices for EVD insertion. No standard practices have been proposed or adopted by the neurosurgical community for EVD insertion or complication avoidance. These results highlight the need for the nationwide standardization of technique and complication prevention measures.


Prehospital Emergency Care | 2018

Prehospital Intubation: Further Confounders in Trial Results

Iqbal Sayeed; Fahim Atif; Claudia Espinosa-Garcia; Bushra Wali; Nefize Turan; Seema Yousuf; Donald G. Stein

Dear Editor, In “Prehospital Intubation is Associated with Favorable Outcomes and Lower Mortality in ProTECT III,” Denninghoff et al. (1) evaluated the relationship between prehospital intubation, functional outcomes, and mortality using data from the patients enrolled in the ProTECT III multicenter, randomized, doubleblind, placebo-controlled trial of early administration of progesterone after traumatic brain injury (2). The authors report that prehospital intubation and air medical transport together were associated with much more favorable outcomes and lower mortality. This observation is interesting and potentially very important for improving emergency services in the field, but their findings also raise concerns regarding how the factors examined in this study may have modified the outcomes of the ProTECT III trial.


Neuroscience | 2017

Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve

Fahim Atif; Megan Prunty; Nefize Turan; Donald G. Stein; Seema Yousuf

We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve. We also examined the regenerative effect of P4 on pathological changes in intra-epidermal nerve fibers (IENF) of the footpads. Diabetes/hyperglycemia led to body weight loss over 5weeks and P4 treatment reduced this loss. At week 5, blood-glucose levels were significantly lower in the P4-treated diabetic group compared to vehicle. Compared to sham or P4-treated groups, the diabetic vehicle group showed hyperactivity on the spontaneous locomotor activity test. Western blot data revealed upregulation of VEGF, IL-6, CD11b, NG2, COX2 and MMP-2 levels in the vehicle group and P4 treatment normalized these expression levels. IENF densities were reduced in the vehicle group and normalized after P4 treatment. We conclude that P4 can reduce some of the chronic pathological responses to STZ-induced diabetes.


Surgical Neurology International | 2016

Intracranial dural arteriovenous fistula as a cause for symptomatic superficial siderosis: A report of two cases and review of the literature

Griffin R. Baum; Nefize Turan; Ferdinando S. Buonanno; Gustavo Pradilla; Raul G. Nogueira

Background: Superficial siderosis (SS) is the occult deposition of hemosiderin within the cerebral cortex due to repeat microhemorrhages within the central nervous system. The collection of hemosiderin within the pia and superficial cortical surface can lead to injury to the nervous tissue. The most common presentation is occult sensorineural hearing loss although many patients have been misdiagnosed with diseases such as multiple sclerosis and amyotrophic lateral sclerosis before being diagnosed with SS. Only one case report exists in the literature describing an intracranial dural arteriovenous fistula (dAVF) as the putative cause for SS. Case Description: We describe two cases of SS caused by a dAVF. Both patients had a supratentorial, cortical lesion supplied by the middle meningeal artery with venous drainage into the superior sagittal sinus. In both patients, symptoms improved after endovascular embolization. The similar anatomic relationship of both dAVFs reported presents an interesting question about the pathogenesis of SS. Similar to the pathologic changes seen in the formation of intracranial arterial aneurysms; it would be possible that changes in the blood vessel lining and wall might predispose a patient to chronic, microhemorrhage resulting in SS. Conclusions: We describe the second and third cases of a dAVF as the cause of SS, and the first cases of successful treatment of SS-associated dAVF with endovascular embolization. As noninvasive imaging techniques become more sensitive and easily obtained, one must consider their limitations in detecting occult intracranial vascular malformations such as dAVF as a possible etiology for SS.


Surgical Neurology International | 2018

The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage

Gustavo Pradilla; JackW Barrow; Nefize Turan; Pasang Wangmo; AnilK Roy

Background: Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating neurological condition with a high risk of associated morbidity and mortality. Inflammation has been shown to increase the risk of complications associated with aSAH such as vasospasm and brain injury in animal models and humans. The goal of this review is to discuss the inflammatory mechanisms of aneurysm formation, rupture and vasospasm and explore the role of sex hormones in the inflammatory response to aSAH. Methods: A literature review was performed using PubMed using the following search terms: “intracranial aneurysm,” “cerebral aneurysm,” “dihydroepiandrosterone sulfate” “estrogen,” “hormone replacement therapy,” “inflammation,” “oral contraceptive,” “progesterone,” “sex steroids,” “sex hormones” “subarachnoid hemorrhage,” “testosterone.” Only studies published in English language were included in the review. Results: Studies have shown that administration of sex hormones such as progesterone and estrogen at early stages in the inflammatory cascade can lower the risk and magnitude of subsequent complications. The exact mechanism by which these hormones act on the brain, as well as their role in the inflammatory cascade is not fully understood. Moreover, conflicting results have been published on the effect of hormone replacement therapy in humans. This review will scrutinize the variations in these studies to provide a more detailed understanding of sex hormones as potential therapeutic agents for intracranial aneurysms and aSAH. Conclusion: Inflammation may play a role in the pathogenesis of intracranial aneurysm formation and subarachnoid hemorrhage, and administration of sex hormones as anti-inflammatory agents has been associated with improved functional outcome in experimental models. Further studies are needed to determine the therapeutic role of these hormones in the intracranial aneurysms and aSAH.


World Neurosurgery | 2017

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage

Nefize Turan; Brandon A. Miller; J. Russell Huie; Robert Allen-James Heider; Jun Wang; Bushra Wali; Seema Yousuf; Adam R. Ferguson; Iqbal Sayeed; Donald G. Stein; Gustavo Pradilla

BACKGROUND Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. METHODS We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. RESULTS PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. CONCLUSIONS PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH.


Surgical Neurology International | 2017

Nontraumatic, posterior circulation pseudoaneurysm of the basilar artery summit with complete spontaneous resolution: Case report and literature review.

Nefize Turan; Shannon Butler; Theodore C. Larson; Alexander Mason

Background: Intracranial pseudoaneurysms are rare vascular defects of arterial walls that are classically the result of traumatic injury, iatrogenic causes, or infection. Idiopathic pseudoaneurysms are seen even less frequently and are often related to atherosclerosis. Pseudoaneurysms are most commonly found along the distal wall of the internal carotid artery, however, can occur at any location in the cerebrovascular circulation. Treatment of these arterial defects is often challenging due to their frail nature. Case Description: A 61-year-old male with a history of hypertension presented with a severe, atypical headache without history of trauma. Computed tomography (CT) and computed tomography angiography (CTA) demonstrated diffuse subarachnoid hemorrhage. Imaging demonstrated a 3.5 mm pseudoaneurysm projecting distally from the basilar artery at the apex. Repeated imaging (CTA, digital subtraction angiography) demonstrated decreased size and flow associated within the aneurysm over the following 2 weeks; as such, the patient was managed conservatively. The patient was discharged in neurologically intact condition when imaging at 14 days confirmed complete and spontaneous resolution of the pseudoaneurysm. Conclusion: Idiopathic pseudoaneurysms that are commonly associated with atherosclerosis are most commonly managed surgically or endovascularly. Conservative approach may be considered in a select group of patients that exhibit decreased size and/or flow within the aneurysm in repeated imaging; spontaneous resolution was seen in the present case.


World Neurosurgery | 2016

Adult Intramedullary Teratoma of the Spinal Cord: A Case Report and Review of Literature

Nefize Turan; Sameer H. Halani; Griffin R. Baum; Stewart G. Neill; Constantinos G. Hadjipanayis

BACKGROUND Teratomas of the spinal cord constitute 0.1% of all spinal tumors, and these lesions are extremely rare in adults. The authors describe a rare case of intradural intramedullary teratoma of the conus medullaris and perform review of literature of intramedullary teratomas seen in the thoracolumbar region. CASE DESCRIPTION A 48-year-old man presented with fasciculations in the bilateral upper and lower extremities. Radiologic findings revealed an L2-L3 level intradural, nonenhancing, extramedullary cystic mass measuring 15 × 13 mm with a 6-mm enhancing nodule at the level of the conus medullaris. The patient was followed up for 1 year, during which time enlargement of the lesion with new areas of patchy contrast enhancement were observed. L1-L2 decompressive laminectomies were performed, and gross total resection of the lesion was achieved. Histopathologic examination confirmed the diagnosis of benign mature cystic teratoma. A literature review revealed no incidence difference in intramedullary teratomas between males and females (P > 0.05). The mean age at the time of diagnosis was 36.4 ± 12.3 years for men and 41.3 ± 11.6 for women (P < 0.05). The mean symptom duration before treatment was 64.6 ± 79.4 months for females and 20.7 ± 13.8 months for men (P < 0.05). Complete resection was achieved in 48.1% of the cases. CONCLUSIONS Teratomas should be taken into consideration in the differential diagnosis of intramedullary lesions when the imaging reveals variable signal intensity because of tissue heterogeneity. A partial resection is a viable treatment option when the lesion is attached to vital structures because of the low recurrence rates reported in the literature.

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