FIG. 6.

Guanabenz reduces cortical tissue loss and improves hippocampal integrity after traumatic brain injury. (A) Representative pictures of brains removed from injured animals treated with vehicle, 5.0 mg/kg of guanabenz initiated 30 min postinjury, 0.5 mg/kg of guanabenz started 30 min postinjury, and delayed administration of 5.0 mg/kg of guanabenz. (B) Summary data showing that 5.0 mg/kg, but not 0.5 mg/kg, of guanabenz significantly reduced cortical tissue loss in controlled cortical impact rats. (C) Representative photomicrographs showing that an absence in NeuN immunoreactivity (arrows) was detected in the cornu ammonis 1 subfield of the ipsilateral hippocampus in all groups, suggesting neuronal death. Accompanying this loss, disrupted microtubule-associated protein 2 (MAP2) immunoreactivity was detected (marked by yellow brackets), a finding indicative of dendritic loss/damage. Scale bar=1 mm. (D) Quantification of the area of MAP2 disruption revealed that animals treated with guanabenz 30 min postinjury, but not 24 h postinjury, had reduced dendritic damage. (E) High-magnification images showing that, in vehicle-treated injured animals, an almost complete loss of MAP2-positive dendrites occurred in the area of dendritic damage. By comparison, in an animal treated with 5.0 mg/kg of guanabenz 30 min postinjury, some sparred fibers can be seen. Scale bar=100 μm. (F) Quantification of relative MAP2 immunoreactivity (fluorescent intensity; FI) in the damaged versus healthy regions of the hippocampus revealed that animals treated acutely postinjury with either 5.0 mg/kg or 0.5 mg/kg of guanabenz had preserved dendrites within the area of damage. Delayed guanabenz treatment had a damaged/healthy FI ratio for MAP2 that was not significantly different than that calculated for vehicle-treated injured controls. Data are presented as the mean±standard error of the mean. *p<0.05. Guan, Guanabenz. Color image is available online at www.liebertpub.com/neu