A new model of congenital hydrocephalus in the rat.
ABSTRACT Hydrocephalic neonates were observed in a small breeding colony of rats. Normal rats from this colony were obtained and brother-sister mated for seven generations. The overall prevalence of hydrocephalics was approximately 23%; however, in one subline, the prevalence approached 50%. Breeding data suggested the trait to be polygenic. Hydrocephalics could be detected at 1-2 days of age, and survived for 4-5 weeks. Dilatation of the ventricles was restricted to the lateral ventricles. No evidence of developmental anomalies was seen within the ventricles. Preliminary evidence suggested that the pathophysiology may be related to poorly developed veins in the periosteal-dural layers and to underdeveloped pia-arachnoid cells. The hydrocephalus was classified as being of the communicating type.
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ABSTRACT: BACKGROUND:: Highly integrated anatomic and functional interactions between the cerebrum and the cerebellum during development have been reported. In our previous study, we conducted a proteome analysis to identify the proteins present in the congenital non-communicating hydrocephalus in the cerebellum. We found higher expression of HMGB-1 in hydrocephalic H-Tx rats. OBJECTIVE:: We studied the expression pattern of HMGB-1 in the cerebellum. METHODS:: We studied congenital hydrocephalic H-Tx rats aged 1 day and 7 days along with age-matched non-hydrocephalic H-Tx and Sprague Dawley (SD) rats as controls. Gene and protein expressions of HMGB-1 in the cerebellum were assayed by real-time polymerase chain reaction and western blotting, respectively; further, immunohistochemical analyses were performed using HMGB-1 (indicator of apoptosis), single-stranded DNA (ssDNA); adhesion factor related with cell migration, HNK-1; and the Purkinje cell-specific antibody, calbindin. RESULTS:: Cytoplasmic HMGB-1 expression observed in Purkinje cells in the 1-day-old hydrocephalic group was stronger than that in the non-hydrocephalic and SD groups. Double fluorescent staining with ssDNA confirmed that Purkinje cells were undergoing apoptosis. HNK-1 expression was lower in the Purkinje cell layer in the 7-day-old rats in the hydrocephalic group, and Purkinje cells were disrupted in comparison to the control groups. Morphological changes in the cerebellum were observed in the 7-day-old rats in the hydrocephalic group as compared to the control groups. CONCLUSION:: Our results suggest that cerebellar neuronal cell damage in the early postnatal period may be related to the higher expression of HMGB-1 in the Purkinje cells.Neurosurgery 11/2012; DOI:10.1227/NEU.0b013e31827fcd83 · 3.03 Impact Factor
Atherosclerosis 10/2011; 218(2). DOI:10.1016/j.atherosclerosis.2011.07.080 · 3.97 Impact Factor
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ABSTRACT: Wistar rats are widely used in biomedical research and commonly serve as a model organism in neuroscience studies. In most cases when noninvasive imaging is not used, studies assume a consistent baseline condition in rats that lack visible differences. While performing a series of traumatic brain injury studies, we discovered mild spontaneous ventriculomegaly in 70 (43.2%) of 162 Wistar rats that had been obtained from 2 different vendors. Advanced magnetic resonance (MR) imaging techniques, including MR angiography and diffusion tensor imaging, were used to evaluate the rats. Multiple neuropathologic abnormalities, including presumed arteriovenous malformations, aneurysms, cysts, white matter lesions, and astrogliosis were found in association with ventriculomegaly. Postmortem microcomputed tomography and immunohistochemical staining confirmed the presence of aneurysms and arteriovenous malformations. Diffusion tensor imaging showed significant decreases in fractional anisotropy and increases in mean diffusivity, axial diffusivity, and radial diffusivity in multiple white matter tracts (p < 0.05). These results could impact the interpretation, for example, of a pseudo-increase of axon integrity and a pseudo-decrease of myelin integrity, based on characteristics intrinsic to rats with ventriculomegaly. We suggest the use of baseline imaging to prevent the inadvertent introduction of a high degree of variability in preclinical studies of neurologic disease or injury in Wistar rats.Journal of Neuropathology and Experimental Neurology 11/2014; DOI:10.1097/NEN.0000000000000140 · 4.37 Impact Factor