Objective: This study sought to evaluate the impact of ceftriaxone, as a potential repurposed drug, in ameliorating motor decline in a unilateral rat 6-hydroxydopamine (6-OHDA) model when initiated 7 days after lesion induction.

Background: The motor deficits of Parkinson’s disease (PD): bradykinesia, resting tremors, postural instability and/or rigidity are predominantly unilateral early at diagnosis, progressing bilaterally as the disease advances. Glutamate excitotoxicity is one of the mechanisms implicated in nigrostriatal neuron loss and resulting motor deficits in PD. Ceftriaxone (cef), an FDA-approved antibiotic which increases glutamate uptake by increasing expression of the glutamate transporter, GLT-1, can improve motor function when administered at the time of lesioning. However, whether this protection can occur when cef is given after motor deficits appear are not known.

Method: Evidence of motor deficits was established by evaluation of forepaw adjustment steps (FAS) in 3-month old male unilaterally 6-OHDA-lesioned (16 μg/4 μl into the left medial forebrain bundle) Sprague-Dawley rats. Cef (200 mg/kg, i.p.) or saline was given intermittently on days 7-13, 21-27, and 35-39 post-lesion with periodic assessment of locomotor function.

Results: FAS revealed a significant decline in right (affected) forepaw use (~50 %) on day 7 post-lesion. A compensatory increase in the use of the left (unaffected) forepaw was observed in both groups on day 7, although this effect was diminished in the saline group by day 14. However, this increase was sustained by cef administration till the end of the study.

Conclusion: Unilateral lesion of the nigrostriatal pathway decreased right forepaw use after 7 days; however, a sustained increase in forepaw use contralateral to lesion was observed in the cef group, an effect that emerged as early as 7 days after initiation of cef regimen. Given that cef was given after evidence of lesion, these results indicate cef efficacy as a potential PD therapy may be related to possibly forestalling the progression of degeneration into the contralateral nigrostriatal pathway, as seen in early stages of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ceftriaxone-improves-motor-function-in-a-rat-hemi-parkinsonian-model-potential-to-delay-bilateral-progression-of-motor-deficits-in-parkinsons-disease/