Transcranial near infrared laser therapy (NILT) to treat acute ischemic stroke: a review of efficacy, safety and possible mechanism of action derived from rabbit embolic stroke studies

摘要

Studies using the rabbit small clot or rabbit large clot embolic stroke models (RSCEM and RLCEM respectively) allowed us to alter a single NILT variable while keeping all other variables constant to investigate the variable's effect on the rabbit's behavioral performance following embolization. In this paper we review results from multiple studies. Using the RSCEM, we found that Continuous Wave (CW) NILT significantly improves behavioral function when NILT is administered up to 6 hour post-embolization at 808nm; a durable effect that can last up to 21 days following a single treatment. Using the RLCEM we found that NILT did not significantly alter intracerebral hemorrhage (ICH) incidence following embolization, and since intravenous (IV) tissue plasminogen activator (tPA) is currently the primary treatment of acute ischemic stroke (AIS), we used the RLCEM to determine the safety profile of NILT in combination with tPA. IV tPA increased ICH incidence by 160%. NILT did not affect the tPA-induced increase in ICH. Lastly, since the cellular mechanising) involved in NILT-mediated neuroprotection have not been elucidated, we measured the effect of CW and Pulse Wave (PW) NILT on cortical adenosine triphosphate (ATP) content as an indicator of improved cellular energetics using the RSCEM. Embolization decreased cortical ATP content by 45% compared to naive rabbits, a decrease that was attenuated by CW NILT (pX).05). Following PW NILT, delivering 5-35 times higher peak cortical irradiances than CW NILT, we measured larger increases in cortical ATP content. This is the first demonstration that NILT significantly increased cortical ATP content in embolized animals.