Methylene Blue Is Neuroprotective against Mild Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Methylene blue (MB) has known energy-enhancing and antioxidant properties. This study tested the hypothesis that MB treatment reduces lesion volume and behavioral deficits in a rat model of mild TBI. In a randomized double-blinded design, animals received either MB (n = 5) or vehicle (n = 6) after TBI. Studies were performed on 0, 1, 2, 7, and 14 days following an impact to the primary forelimb somatosensory cortex. MRI lesion was not apparent 1 h after TBI, became apparent 3 h after TBI, and peaked at 2 days for both groups. The MB-treated animals showed significantly smaller MRI lesion volume than the vehicle-treated animals at all time points studied. The MB-treated animals exhibited significantly improved scores on forelimb placement asymmetry and foot fault tests than did the vehicle-treated animals at all time points studied. Smaller numbers of darkstained Nissl cells and Fluoro-Jade Ò positive cells were observed in the MB-treated group than in vehicle-treated animals 14 days post-TBI. In conclusion, MB treatment minimized lesion volume, behavioral deficits, and neuronal degeneration following mild TBI. MB is already approved by the United States Food and Drug Administration (FDA) to treat a number of indications, likely expediting future clinical trials in TBI.

Apolipoprotein E-Mimetic COG1410 Reduces Acute Vasogenic Edema following Traumatic Brain Injury

“…The lesion volumes were determined as pixels with T2 values higher than the mean plus two standard deviations of the value in the homologous contralesional region. 23 Preparation of brain tissue and protein determination Tissues from each injured hemispheres were separated after CCI or sham injury, weighed and immediately frozen in liquid nitrogen. Tissue samples from each group were lysed in RIPA Lysis Buffer with a protease inhibitor cocktail (05892791001; Roche, Basel, Switzerland) and homogenized at 4°C until lysis was complete.…”

Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

“…Note that the lesion volume and behavioral measures data from vehicle and acute MB treatment groups have been previously published. 25 T 2 , ADC, FA, and CBF in the acute MB treatment group have not been previously published.…”

“…3) Histological data were not included in the current study given that we have previously reported such data and found no significant difference in lesion volume detected by MRI and Nissl or Fluro Jade immunohistology. 25 Future studies will include assessment of neurodegeneration and markers of inflammation.…”

“…24 We previously showed that low-dose MB (1 mg/kg) administered acutely at 1 and 3 h post-TBI in rats reduces lesion volume, neurological deficits, and neuronal degeneration. 25 The aims of this study were to: 1) extend our previous findings to test whether delayed (24 h) MB treatment would show efficacy in reducing lesion and behavioral deficits after an open-skull TBI and 2) determine the effects of MB on magnetic resonance imaging (MRI) parameters (T 2 , apparent diffusion coefficient [ADC], fractional anisotropy [FA], and cerebral blood flow [CBF]) in vehicle, acute, and delayed MB treatment groups. A controlled cortical impact (CCI) was applied over the left primary forelimb somatosensory cortex (S1FL) in rats.…”

“…Comparisons were made with our previously published vehicle and acute MB treatment groups in terms of lesion volume and behavioral measures. 25 Moreover, analysis was also performed on how MB affects T 2 , ADC, FA, and CBF of vehicle, acute and delayed MB treatment groups.…”