Neuroprotective effects of TNF binding protein in focal cerebral ischemia

Brain Res. 1997 Dec 19;778(2):265-71. doi: 10.1016/s0006-8993(97)00981-5.

Abstract

The effect of tumor necrosis factor binding protein (TNFbp) was studied in mice subjected to a permanent middle cerebral artery occlusion (MCAO). TNFbp is a dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp), and binds and inhibits TNF-alpha. TNFbp produced a significant reduction in the cortical infarct volume (22.6 +/- 3.5 mm3 immediately after MCAO; 25.2 +/- 2.4 mm3 1 h after MCAO) compared with vehicle-treated animals (30.3 +/- 3.7 mm3 immediately post MCAO; 31 +/- 3.7 mm3 1 h after MCAO (mean +/- S.D.) when administered intracranially up to 60 min post-occlusion. The neuroprotective effect of TNFbp was sustained in mice for 2 weeks after MCAO. DNA fragmentation at the margin of the cortical infarcts was dramatically reduced in mice treated with TNFbp whereas all control animals showed consistent and obvious DNA fragmentation 2 weeks after MCAO. TNFbp could have therapeutic value for the treatment of ischemic stroke if the problem of delivery to brain can be overcome.

MeSH terms

  • Animals
  • Arterial Occlusive Diseases / pathology
  • Arterial Occlusive Diseases / therapy
  • Biotin
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cerebral Infarction / pathology
  • Cerebral Infarction / therapy
  • Cyclic N-Oxides
  • DNA Fragmentation
  • Deoxyuracil Nucleotides
  • Free Radical Scavengers / pharmacology
  • Interleukin 1 Receptor Antagonist Protein
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neurons / enzymology
  • Neurons / pathology
  • Neuroprotective Agents / metabolism*
  • Neuroprotective Agents / pharmacology
  • Nitrogen Oxides / pharmacology
  • Phosphopyruvate Hydratase / analysis
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins / pharmacology
  • Staining and Labeling
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cyclic N-Oxides
  • Deoxyuracil Nucleotides
  • Free Radical Scavengers
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Neuroprotective Agents
  • Nitrogen Oxides
  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
  • recombinant human tumor necrosis factor-binding protein-1
  • phenyl-N-tert-butylnitrone
  • Biotin
  • Phosphopyruvate Hydratase