Abstract
Abnormal cannabidiol (abn-CBD) exerts neuroprotective effects in vivo and in vitro. In the present study, we investigated the impact of abn-CBD on the glial production of proinflammatory mediators and scar formation within in vitro models. Primary astrocytic-microglial cocultures and astrocytic cultures from neonatal C57BL/6 mice and CB2 receptor knockout mice were stimulated with lipopolysaccharide (LPS), and the concentrations of tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and nitrite were determined. Furthermore, we performed a live cell microscopy-based scratch-wound assay. After LPS stimulation, TNFα, IL-6 and nitrite production was more strongly increased in cocultures than in isolated astrocytes. Abn-CBD treatment attenuated the LPS-induced production of TNFα and nitrite in cocultures, while IL-6 production remained unaltered. In isolated astrocytes, only LPS-induced TNFα production was reduced by abn-CBD. Similar effects were observed after abn-CBD application in cocultures of CB2 knockout mice. Interestingly, LPS-induced TNFα and nitrite levels were far lower in CB2 knockout cultures compared to wildtypes, while IL-6 levels did not differ. In the scratch-wound assay, treatment with abn-CBD decelerated wound closure when microglial cells were present. Our data shows a differential role of abn-CBD for modulation of glial inflammation and astrocytic scar formation. These findings provide new explanations for mechanisms behind the neuroprotective potential of abn-CBD.
Highlights
Acute lesions of the central nervous system (CNS), like traumatic brain injury and stroke, are major public health problems [1,2,3,4]
LPS-treatment led to a strong increase in the production of nitric oxide (NO), tumor necrosis factor α (TNFα) and IL-6 in astrocytic-microglial cocultures (Panels a, c, Figures 1–3)
Differences between wildtype cocultures and isolated astrocytic cultures were smaller for IL-6 than for NO and TNFα
Summary
Acute lesions of the central nervous system (CNS), like traumatic brain injury and stroke, are major public health problems [1,2,3,4]. Acute CNS lesions share common pathophysiological features. The initial detrimental event causing the primary irreversible neuronal insult is followed by the secondary neuronal damage, which is characterized by complex interlocking inflammatory and metabolic cascades, and can strongly aggravate the loss of neurons. Mechanisms of secondary neuronal damage are excitotoxicity, neuroinflammation, blood brain barrier (BBB) disruption, gliosis and leukocyte invasion [6,7,8,9]. The inflammatory response is mainly determined by the local activation of microglial cells and astrocytes [10,11,12]
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