Abstract
Abstract Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.
Highlights
Every effort of treating diseases affecting the brain with medication faces the challenges posed by the highly specialized makeup of intracerebral blood vessels
The surgical procedure was followed by venous tail vein access and injection of 4 % Evans Blue
Our preliminary findings presented here corroborate the assumption that by localized infrared laser illumination of the skull surface, mediating heat diffusion to the particular underlying cortical region, local Brain-Blood-Barrier breakdown can be achieved
Summary
Every effort of treating diseases affecting the brain with medication faces the challenges posed by the highly specialized makeup of intracerebral blood vessels. One current approach to address this apparent paradox of having an effective barrier shielding the brain from external harm and simultaneously providing accessibility of medication to specific targets is to apply focused ultrasound to the targeted brain region and thereby mechanically open the BBB [3]. P. Schlett et al, Localized Opening of the Blood-Brain-Barrier by IR Laser Illumination which extent the surrounding healthy tissue is affected by that treatment [4]. As inconsiderate microdrilling the skull of rodents was shown to cause heat damage in the underlying cortex [7], we hypothesize, that illuminating the brain with sufficient optical energy by 1470 nm infrared laser radiation will cause the same effect. The laser illumination procedure was completed within 5-7 minutes, after which the rat was maintained under anesthesia for one hour to allow sufficient time for Evans Blue diffusion prior to intracardiac perfusion with 4% paraformaldehyde (PFA) and brain extraction
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