Ceftriaxone has a neuroprotective effect in a whole-brain irradiation-induced neurotoxicity model by increasing GLT-1...

Radiation-induced brain injury is a prominent side effect of whole-brain irradiation (IR) due to triggered oxidative and inflammatory processes, often resulting in severe and debilitating cognitive dysfunction and neuronal damage. The development of persistent oxidative stress results from radiation-induced reactive oxygen species. Another result is the initiation of glutamate excitotoxicity, which is closely associated with changes in glutamate levels. Elevated release or reduced glutamate uptake disrupts neuronal homeostasis, leading to oxidative stress, mitochondrial dysfunction, and neuroinflammation. The neuroprotective and antioxidant properties of ceftriaxone (CTX) have been linked to its ability to reduce glutamate excitotoxicity, inflammation, and to modulate oxidative stress.

Twenty-one female Wistar rats were included in the study, and 14 of them underwent whole-brain IR with a single dose of 20 Gy on day 7. Saline and CTX applications continued for 21 days. The animals were divided into three groups: group 1: normal control; group 2: IR + saline; and group 3: IR + CTX. To compare the groups, a one-way analysis of variance (ANOVA) statistical test was employed, with a significance threshold set at p < 0.05.

Ceftriaxone treatment had a positive impact on the results of various assessments, e.g., behavioral tests including the three-chamber sociability test, the open-field test, and passive avoidance learning. It also led to increased counts of hippocampal CA1, CA3, and Purkinje neurons as well as elevated brain levels of brain-derived neurotrophic factor (BDNF), glutamate transporter 1 (GLT-1), and superoxide dismutase (SOD) activity. Conversely, CTX reduced the glial fibrillary acidic protein (GFAP) immunostaining index as well as brain levels of malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α).

Ceftriaxone demonstrated promising effectiveness in mitigating radiation-induced neurocognitive impairments and the deterioration of social memory capacity. This effect is achieved by reducing neuronal loss, oxidative stress, and neuroinflammation in irradiated rat brains. Furthermore, the application of CTX facilitated removal of excess glutamate from synapses, thus preventing glutamate excitotoxicity and protecting neurons from excitotoxic cell death.