Ketamine enhances neurological function through neuronal and plasticity-related protein changes in rats with permanent middle cerebral artery occlusion.

Ketamine (KET) is a drug that has been used as an anesthetic for many years. However, in the last two decades, new properties have been discovered that make it useful in treating various psychiatric and neurological disorders. Ketamine has shown effectiveness in preclinical models and patients with conditions such as depression, Parkinson's disease, and obsessive-compulsive disorder, among others. In the present study, we evaluated the effect of ketamine (KET) (15 mg/kg) administered at 24, 48, and 72 h following permanent middle cerebral artery occlusion (pMCAO) in rats, a model of stroke. Forty male Sprague-Dawley rats (~ 300 g) were randomly assigned to three groups: Sham, pMCAO-Saline, and pMCAO-KET (n = 12 per group). Three rats died during the procedures. Neurological function was assessed using the Bederson score after the final KET administration, 72 h post-occlusion. After the neurological assessment, brains were obtained, and dendritic intersections were measured using Sholl analysis, and GFAP, BDNF, and AMPA protein presence were characterized through immunohistochemistry. Additionally, the expression of the AMPA subunit GRIA1 was evaluated by RT-PCR. Our results indicate that ketamine improves sensorimotor performance after pMCAO, as measured by the Bederson score. We also observed cytoarchitectural changes, including increased dendritic branching following ketamine administration. Moreover, ketamine helped reduce the infarct area and alleviate neuropathological features associated with astrocyte reactivity and microglial infiltration. Also, this was accompanied by plasticity-related changes, evidenced by increased levels of neuroplasticity proteins BDNF and AMPA. These findings suggest that ketamine may be a promising strategy for stroke treatment, with neurobiological changes related to plasticity underlying its effects.