Identification of novel molecular markers for cerebral ischemia

Principal Investigator: Yashar Kalani
Keywords: Stroke , Cerebral Ischemia , Molecular Markers , DNA , RNA Department: Neurosurgery
IRB Number: 00094833 Co Investigator:  
Specialty: Neurosurgery
Sub Specialties: Neurovascular Surgery
Recruitment Status: Recruiting

Contact Information

Yashar Kalani
yashar.kalani@hsc.utah.edu
801-585-6789

Brief Summary

Ischemic stroke is one of the top causes of morbidity and mortality in the United States. Despite a great deal of effort to improve outcomes of patients with ischemic cerebral strokes, the lack of a bona fide animal model representative of cerebral ischemia in man makes the study of the pathological processes involved difficult. Additionally the subtle but significant differences between biology of animal models and the biology of man make translatability of animal results to humans difficult. 

The purpose of this study is to use an iatrogenic model of stroke, meaning those strokes inadvertently caused by endovascular coiling of elective aneurysms, to study the biology of stroke in humans. Clinical evidence suggests that simple catheterization of cerebral vasculature causes small, usually clinically silent embolic strokes. These strokes are evident on MRI scans using the diffusion weighted sequence. Additionally, since the practitioner knows the onset of the elective interventional procedure that led to the stroke, a real-time study of stroke in evolution in man can be performed. MRI evaluation will allow the practitioner to quantify the amount of injury and then correlate this extent of injury with blood-based biomarkers that are differentially expressed before the onset of intervention and after the intervention. A second cohort of patients that will be enrolled are those who present to the emergency room with completed ischemic infarcts that are not amenable to interventional treatment. These patients provide a natural control population for this study. These patients usually present with fixed deficits and in many cases the timing of the onset of symptoms is known. We propose to utilize samples from these two patient populations to study the molecular pathways involved in stroke with the hope of identifying a troponin equivalent for cerebral ischemia. The power of this study rests in the availability of pre-stroke samples (samples prior to intervention), the post-stroke samples (samples in patient who experienced a silent infarct after intervention and those from patients with a completed infarction) and the ability to quantify degree of ischemia using MRI. A third cohort of patients that will be enrolled to serve as additional controls for this study are those who present with spontaneous intracerebral hemorrhage. This patient group is critical because current treatment for ischemic stroke relies in exclusion of intracerebral hemorrhage as etiology of patient's examination findings and deficits. 

Rationale: Global analysis of biological markers is an established mechanism to study complex disease processes. The introduction of microarray technology and the more recent advent of next-generation sequencing approaches have improved our understanding of various biological and disease processes. This revolution has been ongoing since the early 1990s. The rationale for performing these studies is to augment our understanding of the basic mechanisms of stroke in humans. As perviously mentioned, there is no bona fide model of stroke and our experimental design provides a rather simple human model of cerebral ischemia. 

Inclusion Criteria

1. All adult patients that present with ischemic infarcts to the emergency department with a known time of infarct. The time of infarct must be less than 6 hours. 

2. All adult patients with enraptured aneurysms who present for elective endovascular coiling of their aneurysm.

3. All adult patients with spontaneous intracerebral hemorrhage who present for evaluation and treatment. The time of hemorrhage must be less than 24 hours. 

 

Exclusion Criteria

1. Non-adult patients, those that arrive after 6 hours of an infarct (ischemic) or more than 24 hours after hemorrhage or those that are not candidates for further care. 

2. Patients with ruptured aneurysms or other ruptured vascular malformations.