?s abstract): It is hypothesized that the white blood cell genomic response can be used to deduce the presence of neuronal injury due to acute neurological diseases, and that the blood genomic response patterns can be used to differentiate between the diseases causing the neuronal injury. Our preliminary data using microarray technology show unique patterns of gene expression by lymphocytes of adult rats subjected to ischemic strokes, hemorrhagic strokes, status epilepticus, hypoxia, hypoglycemia and sham-surgeries as compared to untouched controls.
The first Aim of this proposal will determine whether short durations of global cerebral ischemia, focal cerebral ischemia (transient ischemic attack), hypoglycemia and seizures produce different white blood cell genomic responses in rats that can be used to differentiate between these conditions hours to days later.
The second Aim will determine whether long durations of global ischemia, hypoglycemia and status epilepticus regulate specific genes in white blood cells in response to the diffuse neuronal injury caused by all of these conditions, and whether these genes can serve as indicators of the diffuse neuronal injury. The genomic expression of neutrophils, lymphocytes and whole blood will be examined at various times after cerebral ischemia, insulin-induced hypoglycemia, seizures and status epilepticus. Genes regulated in the different white blood cells by these conditions will be correlated with the presence of diffuse neuronal cell death in brain using TUNEL staining. The third set of Aims will determine whether the same genes regulated in white blood cells of rodents following single seizures and status epilepticus are also regulated in the white blood cells of men and women patients following seizures and status epilepticus. These studies will also determine whether blood genomic responses can be used to distinguish whether patients have had seizures, pseudoseizures or syncope, and whether some of the neuronal injury-related genes regulated in the blood of rodents with status epilepticus are regulated in patients with status epilepticus. Genes regulated more than two fold on microarrays will be confirmed by quantitative RT-PCR for all of the aims. The goal is to objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to days after they occur; and to begin to identify blood genomic markers of neuronal death associated with acute neurological diseases that might also be useful in chronic neurological diseases.
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