Figure 7.

Neuronal P-tau accumulation and axonal degeneration after TBI in Aqp4^−/− mice. Wild-type and Aqp4^−/− mice were subjected to TBI and the presence of P-tau was evaluated by immunofluorescence 28 d post injury. Double labeling with the AT8 P-tau antibody (specific for pSer202/pThr205 epitopes) and the neuronal marker NeuN showed that in the wild-type cortex, P-tau immunoreactivity was not observed under control conditions (A). After TBI, P-tau immunoreactivity was diffusely increased, but at a low level (B). In the Aqp4^−/− cortex (C), marked P-tau labeling was observed after TBI, both within neuronal soma (arrows) and in surrounding neurites (arrowheads). Quantification of P-tau immunoreactivity in cortical (D) and striatal (E) regions proximal to the traumatic lesion showed that P-tau accumulation was dramatically increased in the Aqp4^−/− brain after TBI. F–K, Axonal degeneration was evaluated in the ipsilateral cortex and underlying corpus callosum 28 d after TBI by staining for phosphorylated neurofilament with the SMI34 monoclonal antibody. In the control cortex (F) and corpus callosum (I), no axonal spheroids or varicosities were evident. In the wild-type cortex after TBI (G), SMI34-immunoreactive varicosities were sparsely present (arrows). In the Aqp4^−/− cortex (H) and corpus callosum (K), SMI34-positive spheroids and varicosities were readily detectable (arrows).