OBJECTIVE: Ceftriaxone has been reported to reduce neuronal damage in 
amyotrophic lateral sclerosis and in an in-vitro model of neuronal ischaemia 
through increased expression and activity of the glutamate transporter, GLT1. We 
tested the effects of ceftriaxone on mortality, neurological outcome, and 
infarct size in experimental stroke in rats and looked for underlying 
mechanisms.
METHODS: Male normotensive Wistar rats received ceftriaxone (200 mg/kg 
intraperitoneal) as a single injection 90 min after middle cerebral artery 
occlusion (90 min with reperfusion). Forty-eight hours after middle cerebral 
artery occlusion, infarct size (MRI) and neurological deficits were estimated. 
GLT1 expression was determined by real time RT-PCR, immunoblotting and promoter 
reporter assay, astrocyte GLT1 activity by measuring glutamate uptake. Bacterial 
load in various organs was measured by real time RT-PCR, neurotrophins and IL-6 
by immunoblotting.
RESULTS: Ceftriaxone dramatically reduced early (24-h) mortality from 34.5% 
(vehicle treatment, n = 29) to 0% (P < 0.01, n = 19). In a subgroup, followed up 
for 4 weeks, mortality persisted at 0%. Ceftriaxone strongly tended to reduce 
infarct size, it significantly improved neuronal survival within the penumbra, 
reduced neurological deficits (P < 0.001) and led to an upregulation of 
neurotrophins (P < 0.01) in the peri-infarct zone. Ceftriaxone did not increase 
GLT1 expression, but increased GLT1 activity (P < 0.05).
CONCLUSION: Ceftriaxone causes a significant reduction in acute stroke mortality 
in a poststroke treatment regimen in animal studies. Improved neurological 
performance and survival may be due to neuroprotection by activation of GLT1 and 
a stimulation of neurotrophins resulting in an increased number of surviving 
neurons in the penumbra.