Neuronal Injury and Blood Genomics

Project: Research project

Description

DESCRIPTION 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.
StatusFinished
Effective start/end date6/1/025/31/07

Funding

  • National Institutes of Health: $359,550.00
  • National Institutes of Health: $359,550.00
  • National Institutes of Health: $355,438.00
  • National Institutes of Health: $348,975.00

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Transient Ischemic Attack
Genomics
Status Epilepticus
Hypoglycemia
Wounds and Injuries
Seizures
Leukocytes
Genes
Acute Disease
Lymphocytes
Vasovagal Syncope
In Situ Nick-End Labeling
Syncope
Rodentia
Blood Cells
Neutrophils
Stroke
Insulin
Staining and Labeling
Technology

ASJC

  • Medicine(all)
  • Neuroscience(all)