Details

Autor(en) / Beteiligte

• Himmelseher, S
• Pfenninger, E
• Kochs, E
• Auchter, M

Titel

S(+)-ketamine up-regulates neuronal regeneration associated proteins following glutamate injury in cultured rat hippocampal neurons

Ist Teil von

• Journal of neurosurgical anesthesiology, 2000-04, Vol.12 (2), p.84-94

Ort / Verlag

United States

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• In previous studies, racemic ketamine improved neurological outcome after experimental brain injury and S(+)-ketamine demonstrated neuroprotective effects in neurons after damage in vitro. We compared the expression of regeneration-associated proteins in rat hippocampal neurons after glutamate injury and treatment with S(+)-ketamine versus racemic ketamine. Following an 8 minute exposure to 100 microM glutamate, neurons were maintained untreated or in the presence of S(+)-ketamine or racemic ketamine (10(-4) M, 10(-5) M, 10(-6) M) for one week. Growth-associated protein-43 (GAP-43) and synaptosomal-associated protein-25 (SNAP-25) was analyzed by Western Blotting, the mitochondrial transmembrane potential (MTP) by fluorescence imaging, and [3H]2-deoxy-D-glucose ([3H]2-DG) uptake by scintillation spectrometry. Seven days after exposure, GAP-43 decreased to 15% and SNAP-25 to 30% in the glutamate-injured, untreated neurons. The MTP declined to 50% and [3H]2-DG to 30%. Both S(+)-ketamine and racemic ketamine at 10(-4) M and 10(-5) M minimized the decline in MTP, almost maintaining it at control value. Additionally, S(+)-ketamine and racemic ketamine decreased the reduction in [3H]2-DG. S(+)-ketamine at 10(-4) M and 10(-5) M and racemic ketamine at 10(-4) M reduced the decline in SNAP-25 to 60% of controls (P < .05). However, S(+)-ketamine at 10(-4) M and 10(-5) M only reversed the decrease in GAP-43 to 50% and 40% of controls, respectively (P < .05). We conclude that the synthesis of a growth-associated protein related to plasticity and repair in the adult nervous system is increased by S(+)-ketamine but is not increased by racemic ketamine.