Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia

Eur J Neurosci. 2002 Jun;15(12):1937-52. doi: 10.1046/j.1460-9568.2002.02030.x.

Abstract

RNA expression profiles in rat brain were examined 24 h after ischemic stroke, intracerebral haemorrhage, kainate-induced seizures, insulin-induced hypoglycemia, and hypoxia and compared to sham- or untouched controls. Rat oligonucleotide microarrays were used to compare expression of over 8000 transcripts from three subjects in each group (n = 27). Of the somewhat less than 4000 transcripts called 'present' in normal or treated cortex, 5-10% of these were up-regulated 24 h after ischemia (415), haemorrhage (205), kainate (187), and hypoglycemia (302) with relatively few genes induced by 6 h of moderate (8% oxygen) hypoxia (15). Of the genes induced 24 h after ischemia, haemorrhage, and hypoglycemia, approximately half were unique for each condition suggesting unique components of the responses to each of the injuries. A significant component of the responses involved immune-process related genes likely to represent responses to dying neurons, glia and vessels in ischemia; to blood elements in haemorrhage; and to the selectively vulnerable neurons that die after hypoglycemia. All of the genes induced by kainate were also induced either by ischemia, haemorrhage or hypoglycemia. This strongly supports the concept that excitotoxicity not only plays an important role in ischemia, but is an important mechanism of brain injury after intracerebral haemorrhage and hypoglycemia. In contrast, there was only a single gene that was down-regulated by all of the injury conditions suggesting there is not a common gene down-regulation response to injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Cells / metabolism
  • Blood Cells / pathology
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Brain Chemistry / genetics*
  • Brain Ischemia / genetics*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / physiopathology
  • Cluster Analysis
  • Down-Regulation / physiology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Genome
  • Hypoglycemia / genetics*
  • Hypoglycemia / metabolism
  • Hypoglycemia / physiopathology
  • Hypoxia, Brain / genetics*
  • Hypoxia, Brain / metabolism
  • Hypoxia, Brain / physiopathology
  • Male
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / genetics*
  • Seizures / metabolism
  • Up-Regulation / physiology

Substances

  • RNA, Messenger