Nano-Pulsed Laser Therapy Is Neuroprotective in a Rat Model of Blast-Induced Neurotrauma

Abstract

We have developed a novel, non-invasive nano-pulsed laser therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma (BINT) to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head 1 h after injury using a specially developed fiber-optic system. Vestibulomotor function was assessed on post-injury days (PIDs) 1–3 on the beam balance and beam walking tasks. Cognitive function was assessed on PIDs 6–10 using a working memory Morris water maze (MWM) test. BDNF and caspase-3 messenger RNA (mRNA) expression was measured by quantitative real-time PCR (qRT-PCR) in laser-captured cortical neurons. Microglia activation and neuronal injury were assessed in brain sections by immunofluorescence using specific antibodies against CD68 and active caspase-3, respectively. In the vestibulomotor and cognitive (MWM) tests, NPLT-treated animals performed significantly better than the untreated blast group and similarly to sham animals. NPLT upregulated mRNA encoding BDNF and downregulated the pro-apoptotic protein caspase-3 in cortical neurons. Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after traumatic brain injury (TBI).

Silencing of A20 Aggravates Neuronal Death and Inflammation After Traumatic Brain Injury: A Potential Trigger of Necroptosis

“…6-point scale method and four consecutive trials per session were used to evaluate for the rat motor ability (Esenaliev et al, 2018). The rats were trained to balance for 60 s on a short wooden beam (50 × 1.5 × 4 cm) raised 90 cm off the floor.…”

The Role of BDNF in Experimental and Clinical Traumatic Brain Injury

“…Increased by treatment. Neurological severity score (Xuan et al 2015) [ 136 ] 10/group Mouse CCI Immunofluorescence staining Cortex and hippocampus 7 and 28 days Not altered by trauma, increased by treatment Neurological severity score (Wu et al 2016) [ 74 ] 12/grp Rat CCI Western blot Cortex 24 h Decreased by trauma, increased by treatment Neurological severity score (Colak et al 2012) [ 43 ] 15/grp Rat CHI Quantitative real-time PCR and whole genome microarray Frontal and parietal brain tissues 1, 12 and 48 h Increased at 1h and at 12 h compared to control group, decreased at 48 h. Not performed (Shah et al 2006) [ 137 ] 4/group Mouse FPI Real-time PCR Hippocampus 1 day Not altered by trauma Not performed (Esenaliev et al 2018) [ 138 ] 3–4/grp …”

Photobiomodulation (660 nm) therapy reduces oxidative stress and induces BDNF expression in the hippocampus

“…Various studies have been carried out to increase the expression of BDNF using light. For example, nano-pulsed laser therapy was applied in rats to show that BDNF expression can be increased by a noninvasive method 19,20 . Moreover, PBMT increased the expression of BDNF in amyloid beta-treated neurons and hippocampal cells, thus inhibiting neuronal damage and inducing dendritic cell activity 21 .…”