The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia

Abstract

Ampicillin, a β-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G signifi cantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats

“…Metronidazole and meropenem are more likely to enter the CNS and affect the function of microglia and play a role in cerebral haemorrhage, brain trauma and other neurological diseases. Ampicillin has been reported to dose-dependently protect neurons against ischaemic brain injury, to attenuate the activity of matrix metalloproteinases and to reduce immunoreactivities of astrocytes and microglia by increasing the level of glutamate transporter-1 39. Ciprofloxacin also was claimed to inhibit the activation of the TLR4/NF-κB signalling pathway 40.…”

“…Ampicillin has been reported to dose-dependently protect neurons against ischaemic brain injury, to attenuate the activity of matrix metalloproteinases and to reduce immunoreactivities of astrocytes and microglia by increasing the level of glutamate transporter-1. 39 Ciprofloxacin also was claimed to inhibit the activation of the TLR4/NF-κB signalling pathway. 40 Thus, GF mice may have been a more ideal model in which to conduct these experiments.…”

Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia

“…Mice with tIsc were prepared according to the method of Lee et al (2016). Each group consisted of eight mice.…”

Cognitive- and memory-enhancing effects of Augmentin in Alzheimer’s rats through regulation of gene expression and neuronal cell apoptosis

“…Augmentin has widely been used to treat bacterial diseases ( Lopes-de-Campos et al, 2019 ). Ampicillin has been investigated as a neuroprotective agent, and it protected neurons from the damaging effects of ischemic brain damage in a dose-dependent manner ( Lee et al, 2016 ). Inducing the glutamate transporter 1 (GLT-1) protein and decreasing the activity of matrix metalloproteinase (MMP) in the mouse hippocampus are the two mechanisms through which ampicillin provides protection against ischemia‒reperfusion brain injury ( Lee et al, 2016 ).…”

“…Ampicillin has been investigated as a neuroprotective agent, and it protected neurons from the damaging effects of ischemic brain damage in a dose-dependent manner (Lee et al, 2016). Inducing the glutamate transporter 1 (GLT-1) protein and decreasing the activity of matrix metalloproteinase (MMP) in the mouse hippocampus are the two mechanisms through which ampicillin provides protection against ischemia-reperfusion brain injury (Lee et al, 2016). It has been demonstrated that the psychoactive substance clavulanic acid can change how the central nervous system functions.…”