We assume that the hydrocephalus and enlarged brain volume were not TBI related. Rather, they were pre-existing, resembling a case recently reported on by Ferris and colleagues, who reported a 1.8-fold increase in brain volume of a 2-year-old R222 RNaseT2 knockout rat with severe "spontaneous hydrocephalus." The etiology of the "pre-existing" hydrocephalus (e.g., genetic) in rat #112 is unknown; another question is how a brain twice the volume of the normal brain could fit into the regular-sized skull. Ferris and colleagues did not report any abnormalities in skull size or shape either, even though the skull appears larger than normal in magnetic resonance imaging (MRI) shown in their Figure 1. Because we did not perform any structural MRI, we cannot conclude whether the thin cortex of rat #112 was folded within the skull or whether the skull was thinner, giving the brain more space.
Hydrocephalus can be defined as a pathological increase in cerebral ventricular volume caused by impaired absorption or increased production of cerebrospinal fluid. Edwards and colleagues identified hydrocephalus in 31 of 35 hamsters without a dome-shaped skull. The lack of doming suggested that the condition in the hamster cohort developed after suture closure. In another study, hydrocephalic Wistar rats displayed abnormalities in the ventricular and vascular systems, including aneurysms, intracranial cysts, white matter injury, tissue necrosis, and excessive astrogliosis surrounding the ventricles and blood vessels. We observed no doming of the skull in rat #112; nor did we observe any compression of the ventricular system or the Sylvian aqueduct. Iron deposits in the choroid plexus, which were recently associated with post-TBI ventricle enlargement, were detected in all rats of the cohort with TBI. Therefore, we consider post-injury choroidal hemorrhage as an unlikely etiological factor for the robust ventriculomegaly in rat #112.
Gross anatomical analysis of the brain of rat #112 revealed a very thin cerebral cortex. Contrary to our expectations, the cortical volume of rat #112 was 127% that of the cohort mean. We have compared the cortical volume rat #112 to other TBI-induced rats in the same cohort, rather than to naive or sham-operated control rats. Further studies are needed to explore whether the cortical volume increase is related to intracortical edema and/or gliosis or simply to stretching of the cortical tissue surrounding the enlarged ventricles. Interestingly, Ferris and colleagues reported a 7% reduction in cortical volume in the R222 RNaseT2 KO rat with severe spontaneous hydrocephalus.