Use of Ceftriaxone in Treating Cognitive and Neuronal Deficits Associated With Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is caused by accumulation of Lewy bodies, destruction of mitochondria, and excess of glutamate in synapses, which eventually leads to excitotoxicity, neurodegeneration, and cognitive impairments. Ceftriaxone (CEF) reduces excitotoxicity by increasing glutamate transporter 1 expression and glutamate reuptake. We investigated whether CEF can prevent cognitive decline and neurological deficits and increase neurogenesis in DLB rats. Male Wistar rats infused with viral vector containing human alpha-synuclein (α-syn) gene, SNCA, in the lateral ventricle were used as a rat model of DLB. CEF (100 mg/kg/day, i.p.) was injected in these rats for 27 days. The active avoidance test and object recognition test was performed. Finally, the brains of all the rats were immunohistochemically stained to measure α-syn, neuronal density, and newborn cells in the hippocampus and substantia nigra. The results revealed that DLB rats had learning and object recognition impairments and exhibited cell loss in the nigrostriatal dopaminergic system, and hippocampal CA1, and dentate gyrus (DG). Additionally, DLB rats had fewer newborn cells in the DG and substantia nigra pars reticulata and more α-syn immune-positive cells in the DG. Treatment with CEF improved cognitive function, reduced cell loss, and increased the number of newborn cells in the brain. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of DLB rats. CEF may therefore has clinical potential for treating DLB.

Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is characterized by neuronal deficits and α-synuclein inclusions in the brain. Ceftriaxone (CEF), a ß-lactam antibiotic, has been suggested as a therapeutic agent in several neurodegenerative disorders for its abilities to counteract glutamate-mediated toxicity and to block α-synuclein polymerization. By using manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemistry, we measured the effects of CEF on neuronal activity and α-synuclein accumulation in the brain in a DLB rat model. The data showed that CEF corrected neuronal density and activity in the hippocampal CA1 area, suppressed hyperactivity in the subthalamic nucleus, and reduced α-synuclein accumulation, indicating that CEF is a potential agent in the treatment of DLB.

Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.