Delayed treatment with the mGluR5 agonist, CHPG, reduces lesion volume and increases white matter integrity after TBI. (A) Lesion volume was assessed using T2-weighted MRI in TBI mice. One month post-injury, all TBI mice had significant and comparable lesions volumes and were subsequently randomized and treated with vehicle, CHPG or MTEP + CHPG. TBI-induced lesion volumes significantly increased over three months in the vehicle-treated TBI group (*P < 0.05 versus one month), whereas the lesions in the CHPG-treated TBI group did not expand and were significantly reduced at three months post-injury when compared to the vehicle-treated TBI group (+P < 0.05 versus vehicle). TBI mice that received MTEP co-administration with CHPG had lesion volumes that were not significantly different compared to vehicle-treated TBI levels (n = 6 per group). (B) Representative MRI images show hyperintense lesion areas from the lesion epicenter and rostral/caudal regions at three months post-injury for each treatment group. (C)
Ex vivo DTI was performed at four months post-injury. White matter tracts of interest were outlined in either color or FA images (Ci) on both the ipsilateral (pink) and contralateral (brown) sides. The ratio of the ipsilateral mean diffusivity (Cii) and FA (Ciii) to contralateral measurements demonstrate that CHPG treatment significantly reduced mean diffusivity and increased FA (*P < 0.05, n = 5). (D) White matter tracts were outlined (Di) to determine fiber volume (Diii). Three-dimensional visual representations are presented in (Dii). A naïve sample demonstrates the standard volume of white matter tracts in uninjured tissue. TBI resulted in a marked reduction in white matter volume. Fiber volume was significantly increased in CHPG-treated TBI tissue when compared to vehicle-treated TBI tissue (*P < 0.05, n = 5). Statistical analysis was by two-way ANOVA with Bonferroni t-test post-hoc corrections in (A), Mann-Whitney U test in (Cii), and Student's t-test in (Ciii) and (Diii). Bars represent mean ± SEM.