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Researchers break the brain’s protective barrier open and deliver drugs to the brain

A new technique for getting medication past the hard-to-cross blood-brain barrier is opening new avenues for the treatment of central nervous system diseases.

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The brain has an entire arsenal of weapons to protect itself from damage. Cerebrospinal fluid, a protective membrane and – the most obvious – the skull defend it against physical injury. However, for protection against disease-causing pathogens and toxins in the blood, the brain relies on a specialised system of cells called the blood-brain barrier. The blood-brain barrier acts as a boundary between the blood vessels and brain tissue, not only shielding the brain from toxic substances in the bloodstream, but also supplying it with nutrients. However, its very effectiveness in preventing unwanted substances from entering the brain is what makes getting medication past it so difficult and the treatment of brain and central nervous system diseases such a challenge. Researchers supported in part by the EU-funded V-EPC project have found a new way to open the blood-brain barrier temporarily in order to deliver medication to the brain. Their technique makes use of light and nanoparticles to pry apart the tight junctions formed by the closely wedged cells in the blood-brain barrier’s capillaries, allowing the drug to cross the barrier and reach its target.

Potential treatments

The team of researchers from Ireland, Italy and the United States used mice to demonstrate the new method, which is described in their study published in the journal ‘Nano Letters’. According to a news release posted on ‘ScienceDaily’, the study’s corresponding author Dr Zhenpeng Qin of the University of Texas at Dallas (UT Dallas) believes that the approach could lead to treatments for brain tumours and Lou Gehrig’s disease. It could also aid in stroke recovery and deliver gene therapy. However, it needs further development and testing before it can be used in humans. “Approaches to increase blood-brain barrier [BBB] permeability are essential to advance therapeutics for central nervous system diseases,” states UT Dallas biomedical engineering PhD student and study co-lead author Xiaoqing Li in the same news release. In the study, the researchers synthesised gold nanoparticles and conjugated them with the antibody BV11 to target the tight junctions. They intravenously injected adeno-associated viruses (or AAVs, used in gene therapy) and applied laser stimulation. The result shows that AAVs crossed the blood-brain barrier and infected 64 % of neurons in the right hemisphere with laser excitation. This demonstrates that transcranial picosecond laser stimulation of the gold nanoparticles following the intravenous injection makes the barrier more permeable. The action of applying laser pulses to activate the nanoparticles “produces a tiny mechanical force that temporarily breaks the barrier open so a drug can enter the blood flow into the brain,” explains Li. However, this action does not damage the barrier, nor does it adversely affect blood vessel constriction and dilation. Another study supported by the V-EPC (Inherited disfunctions of brain microcirculation) project describes the formation of cavernomas – clusters of abnormal blood vessels that form in the brain and spinal cord – in mice. The study provides a preclinical mouse model for the development of new drugs to treat acute haemorrhage in the brain and spinal cord caused by cavernomas. The study was published in the journal ‘iScience’. For more information, please see: V-EPC project

Keywords

V-EPC, brain, blood, blood-brain barrier, central nervous system, nanoparticle, laser pulse