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Abstract
BackgroundBacterial melanin has been proven to stimulate regeneration after CNS lesions. The purpose of this study was to test, whether bacterial melanin can enter the brain via the blood–brain barrier (BBB).MethodsBacterial melanin (BM) was radioactively labeled by the iodobead method and used to test the BBB permeability after systemic injection into rats. The unidirectional influx rate from the blood was calculated by multiple-time regression analysis. A subgroup of the animals was co-injected with non-labeled BM to determine if BM has a saturable transport across the BBB. The levels of radioactivity were determined in the serum and tissues. Arterial blood was sampled to obtain the level of I-BM at different time points after injection. After systemic perfusion with saline, animals were decapitated and brain, spinal cord, liver and kidney samples were obtained and homogenized to test the I-BM level.ResultsStudy results showed that radioactively-labeled bacterial melanin crossed the BBB, was enzymatically stable in blood and in brain parenchyma. Entry to brain was reduced when non-labeled BM was also present. Circulating melanin entered all regions of the CNS but the uptake was higher in lumbar spinal cord, thalamus, hypothalamus and substantia nigra. Liver and kidneys had high uptake rates of BM.ConclusionsThese results show that bacterial melanin has saturable transport across the BBB and selectively targets some CNS regions. Such transport may contribute to the neuroprotective action of bacterial melanin.
Highlights
Bacterial melanin has been proven to stimulate regeneration after CNS lesions
In a previous experimental series, we have shown the neuroprotective action of Bacterial melanin (BM) after neurotrauma in the CNS in that BM accelerates motor recovery and enhances regeneration after substantia nigra lesions [22]
The degradation rate of I-BM was significantly lower in 5 min 20 min 30 min 45 min 60 min 122 ± 3.6 118 ± 1.8 112 ± 1.6 107 ± 1.4 104 ± 0.90 (% of control)
Summary
The purpose of this study was to test, whether bacterial melanin can enter the brain via the blood–brain barrier (BBB). Peptide and protein drugs have shown great potential for the treatment of various neurodegenerative diseases. A major challenge in the pharmacokinetics of such drugs is the delivery of peptides or proteins across the blood–brain barrier (BBB). The lack of effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential neuroprotective agents, has led to the present situation in neurotherapeutics. As a result there are few effective treatments for the majority of neurodegenerative disorders This situation can be changed by an accelerated effort to create a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain
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