Neuroprotective activity of sub-anesthetic ketamine in a preclinical model of Parkinson's disease is not blocked by antagonizing brain-derived neurotrophic factor signaling

Sub-anesthetic ketamine (20 mg/kg, i.p.) given before striatal 6-OHDA is neuroprotective in a progressive rat Parkinson’s model, yielding near complete protection from parkinsonian motor deficits.

• Why it matters: The work addresses whether ketamine’s prior BDNF/TrkB-linked neuroprotection in rats extends to progressive degeneration, and whether TrkB signaling is required for behavioral benefit.
• What they did: Rats received ketamine before striatal 6-OHDA, and neuroprotection was assessed behaviorally alongside TH preservation and stereology of SNc dopamine neurons; TrkB involvement was tested with ANA-12 and measured by in situ hybridization and semi-quantitative western analysis.
• The result: Ketamine produced robust motor improvement despite only modest TH preservation (~50–60% loss) and no significant TH or SNc dopamine neuron differences; adding ANA-12 did not block protection and reduced TrkB receptor expression only on the lesioned SNc hemisphere, indicating ketamine’s effects are not mediated by TrkB/BDNF signaling.