Increase in peripheral benzodiazepine receptors and loss of glutamate NMDA receptors in a mouse model of closed head injury: a quantitative autoradiographic study.

Abstract

Increases in peripheral type benzodiazepine receptors (PTBR) have been utilized for the detection of neuroinflammation and neurotoxicity in the brain. We have investigated the relationship between PTBR and NMDA receptor binding density in mice with closed head injury (CHI) using quantitative autoradiography. CHI was induced by a weight drop in nine mice, four of which received a single injection of the rat sarcoma (Ras) inhibitor famesyl thiosalicylate (FTS) 1 h after the insult. Sham controls received anesthesia but no contusion. The neurological status of the mice was evaluated at 1 h, and hence up to 7 days using a neurological severity score (NSS). Animals were killed 7 days after CHI and consecutive brain sections were incubated with [3H]PK11195, a PTBR antagonist, or [3H]MK801, an n-methyl-d-aspartate receptor (NMDAR) use-dependent antagonist. CHI produced large (two- to threefold), widespread increases in PK11195 binding in the traumatized hemisphere and a significant decrease (20%-40%) in NMDAR binding limited to regions at close proximity to the lesion. Histologically, these regions were characterized by glial proliferation and neuronal loss. Significant increases in PTBR binding, but no concomitant decrease in NMDAR, were identified in several regions remote from the lesion, including the contralateral ventrolateral striatum and the ipsilateral ventral thalamus. Drug treatment significantly improved the neurological deficits but had only a marginal effect on PTBR. These results support a complex role for glial activation and PTBR increases in the context of CHI.

• Authors: R Grossman, E Shohami, A Alexandrovich, I Yatsiv, Y Kloog, A Biegon
• Journal: NeuroImage (Neuroimage) Vol. 20 Issue 4 Pg. 1971-81 (Dec 2003) ISSN: 1053-8119 [Print] United States
• PMID: 14683703 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Benzoates
• Excitatory Amino Acid Antagonists
• Isoquinolines
• Receptors, GABA-A
• Receptors, N-Methyl-D-Aspartate
• Sulfhydryl Compounds
• 2-thiosalicylic acid
• Thimerosal
• Glutamic Acid
• Farnesol
• Dizocilpine Maleate
• PK 11195

Topics

• Animals
• Antioxidants (pharmacology)
• Autoradiography
• Benzoates (pharmacology)
• Brain (pathology)
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Farnesol (analogs & derivatives, pharmacology)
• Glutamic Acid (physiology)
• Head Injuries, Closed (metabolism, pathology, physiopathology)
• Image Interpretation, Computer-Assisted
• Isoquinolines (pharmacology)
• Mice
• Neuroglia (metabolism)
• Receptors, GABA-A (drug effects, metabolism)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, metabolism)
• Sulfhydryl Compounds
• Thimerosal