Abstract
Purpose: Ceftriaxone, a β-lactam antibiotic, can selectively enhance the expression of glutamate transporter 1 (GLT1), the most abundant astrocytic glutamate transporter expressed in the cortex. It has been found to have neuroprotective effects when administered prior to brain ischemic damage or during the acute phase post-stroke, but its effects in chronic period have not been examined. Methods: We examined the effects of ceftriaxone on the acquisition of motor skill and the functional outcome after focal ischemic cortical lesions. In adult male rats, ceftriaxone (200 mg/kg) or vehicle was intraperitoneally injected daily for 5 days, a treatment regime previously established to upregulate GLT-1. This preceded 28 days of skilled reach training in intact animals or began 3 days following lesions, followed by 5 weeks of rehabilitative reach training. Results: In intact rats, ceftriaxone did not affect skill learning rate or final performance. Following ischemic lesions, though there was no significant difference in lesion sizes between groups, ceftriaxone exacerbated initial deficits in reaching performance. Conclusion: These findings of detrimental effects on motor functional outcome suggest that ceftriaxone may be more useful for neuroprotection during the acute phase of ischemia than for functional recovery in the post-acute period after ischemic damage.