Ceftriaxone improves spatial learning and memory in chronic cerebral hypoperfused rats

Abstract

Cerebral hypoperfusion is associated with cognitive decline in ageing, mild cognitive impairment, vascular type dementia, and Alzheimer's disease. The mechanisms leading to such neurological impairments are still uncertain. Although several mechanisms have been proposed as contributing factors leading to neuronal injury, glutamate excitotoxicity seems to be the relevant one. Recently, it was found that β-lactam antibiotics such as ceftriaxone show a neuroprotective effect by upregulation of glutamate transporter and reduction of glutamate excitotoxicity. To study the contribution of glutamate excitotoxicity and the effects of ceftriaxone on spatial learning and memory in chronic cerebral hypoperfusion, we conducted experiments in rats subjected to permanent bilateral common carotid artery occlusion. Ceftriaxone (200 mg/kg) was injected daily in rats for 5 days after the onset of the arterial ligation. A Morris water maze was used to assess learning and memory two months after arterial ligation. Hippocampal histology and glutamate transporter 1 (GLT-1) expression were also studied. Results showed that ceftriaxone improved learning and memory performance. Consistently, the histological study showed an increase hippocampal CA1 and CA3 neuronal numbers in the ceftriaxone-treated group compared with the vehicle-treated group. Although not statistically significant, the GLT-1 protein level in the hippocampus was 86% higher than the sham group. We conclude that ceftriaxone treatment can attenuate neuronal injury and improve spatial learning and memory after chronic cerebral hypoperfusion and that glutamate excitotoxicity may play an important role in the pathophysiology of chronic cerebral hypoperfusion.

Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats

“…Activated NF-kB binds to the GLT-1 promoter region and upregulates the transcription of this gene [45], thereby decreasing glutamate concentration in the synaptic cleft and alleviating the potentially neurotoxic effects of excess glutamate [46]. In some studies, it was also found that CEF treatment can attenuate neuronal injury and improve spatial learning and memory [47]. In some studies, CEF was also reported to mediate activation of glutathione through increased nuclear factor erythroid 2-related factor 2 (Nrf2) [48].…”

Reactive Astrocytes as Drug Target in Alzheimer’s Disease

“…Ceftriaxone mediated increased expression of GLT1 is possibly NF- Κ B mediated GLT1 promoter activation [ 56 ]. Ceftriaxone was found to improve spatial learning and memory in chronically cerebral hypoperfused rats suggesting role in AD [ 57 ]. Moreover, ceftriaxone decreased tau pathology and showed improvement in cognitive functions [ 58 ].…”

The protective effect of Thai Herbal Sahatsatara formula against white matter injury after chronic cerebral hypoperfusion in middle-aged rats

“…All rats were anesthetized with an intraperitoneal injection of ketamine (60 mg/kg) and xylazine (0.6 mg/kg) mixture [22]. After the rats were unconscious, the neck region was cleansed with 70% alcohol.…”