NAAG Peptidase Inhibitor Reduces Acute Neuronal Degeneration and Astrocyte Damage following Lateral Fluid Percussion TBI in Rats
| Autor: | Joseph H. Neale, Xueren Zhao, Bruce G. Lyeth, Jayaprakash Sarva, Alan P. Kozikowski, Chunlong Zhong |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Glutamate Carboxypeptidase II
Male medicine.medical_specialty Excitotoxicity Hippocampus Biology Receptors Metabotropic Glutamate medicine.disease_cause Neuroprotection Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Glutamate carboxypeptidase II Animals Urea Neurotransmitter Cell Death Dose-Response Relationship Drug Glutamate receptor Rats Neuroprotective Agents Endocrinology medicine.anatomical_structure chemistry Metabotropic glutamate receptor Astrocytes Brain Injuries Anesthesia Nerve Degeneration Neurology (clinical) Astrocyte |
| Zdroj: | Journal of Neurotrauma. 22:266-276 |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2005.22.266 |
| Popis: | Traumatic brain injury (TBI) produces a rapid and excessive elevation in extracellular glutamate associated with excitotoxicity and secondary brain pathology. The peptide neurotransmitter Nacetylaspartylglutamate (NAAG) suppresses glutamate transmission through selective activation of presynaptic Group II metabotropic glutamate receptor subtype 3 (mGluR3). Thus, inhibition of NAAG peptidase activity and the prolong presence of synaptic NAAG were hypothesized to have significant potential for cellular protection following TBI. In the present study, a novel NAAG peptidase inhibitor, ZJ-43, was used in four different doses (0, 50, 100, or 150 mg/kg). Each dose was repeatedly administered i.p. (n=5/group) by multiple injections at three times (0 time, 8 h, 16 h) after moderate lateral fluid percussion TBI in the rat. An additional group was co-administered ZJ-43 (150 mg/kg) and the Group II mGluR antagonist, LY341495 (1 mg/kg), which was predicted to abolish any protective effects of ZJ-43. Rats were euthanized at 24 h after TBI, and brains were processed with a selective marker for degenerating neurons (Fluoro-Jade B) and a marker for astrocytes (GFAP). Ipsilateral neuronal degeneration and bilateral astrocyte loss in the CA2/3 regions of the hippocampus were quantified using stereological techniques. Compared with vehicle, ZJ-43 significantly reduced the number of the ipsilateral degenerating neurons (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|