Blood genomic expression profile for neuronal injury.
This study determined whether stroke and other types of insults produced a gene expression profile in blood that correlated with the presence of neuronal injury. Adult rats were subjected to ischemic stroke, intracerebral hemorrhage, status epilepticus, and insulin-induced hypoglycemia and compared with untouched, sham surgery, and hypoxia animals that had no brain injury. One day later, microarray analyses showed that 117 genes were upregulated and 80 genes were downregulated in mononuclear blood cells of the "injury" (n = 12) compared with the "no injury" (n = 9) animals. A second experiment examined the whole blood genomic response of adult rats after global ischemia and kainate seizures. Animals with no brain injury were compared with those with brain injury documented by TUNEL and PANT staining. One day later, microarray analyses showed that 37 genes were upregulated and 67 genes were downregulated in whole blood of the injury (n = 4) animals compared with the no-injury (n = 4) animals. Quantitative reverse transcription-polymerase chain reaction confirmed that the vesicular monoamine transporter-2 increased 2.3- and 1.6-fold in animals with severe and mild brain injury, respectively, compared with no-injury animals. Vascular tyrosine phosphatase-1 increased 2.0-fold after severe injury compared with no injury. The data support the hypothesis that there is a peripheral blood genomic response to neuronal injury, and that this blood response is associated with a specific blood mRNA gene expression profile that can be used as a marker of the neuronal damage.
Tang
Yang
Y
Department of Neurology, Neuroscience Program, University of Cincinnati, Vontz Center for Molecular Studies-Room 2327, 3125 Eden Avenue, Cincinnati, OH 45267-0536, USA. tangyy@email.uc.edu
Nee
Alex C
AC
Lu
Aigang
A
Ran
Ruiqiong
R
Sharp
Frank R
FR
D000818:Animals; D001790:Blood Physiological Phenomena; D001927:Brain Diseases / Q000097:blood* / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D016678:Genome; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009000:Monocytes / Q000502:physiology; D009479:Neuropeptides; D020411:Oligonucleotide Array Sequence Analysis; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases; D007608:Kainic Acid