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.
"All procedures conducted in this study were approved by the Animal Care and Use Committee of Wayne State University. A colony of H-Tx rats, which develop congenital hydrocephalus due to a closure of their cerebral aqueduct between embryonic day 18 and postnatal day 5 [20-25], was maintained at Wayne State University. Hydrocephalus progresses rapidly in these animals, and by 21 days of age they become severely hydrocephalic. "
[Show abstract][Hide abstract] ABSTRACT: Reactive astrocytosis and microgliosis are important features of the pathophysiology of hydrocephalus, and persistent glial "scars" that form could exacerbate neuroinflammation, impair cerebral perfusion, impede neuronal regeneration, and alter biomechanical properties. The purpose of this study was to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce gliosis in the H-Tx rat model of congenital hydrocephalus.
Minocycline (45 mg/kg/day i.p. in 5% sucrose at a concentration of 5-10 mg/ml) was administered to hydrocephalic H-Tx rats from postnatal day 15 to day 21, when ventriculomegaly had reached moderate to severe stages. Treated animals were compared to age-matched non-hydrocephalic and untreated hydrocephalic littermates. The cerebral cortex (both gray matter laminae and white matter) was processed for immunohistochemistry (glial fibrillary acidic protein, GFAP, for astrocytes and ionized calcium binding adaptor molecule, Iba-1, for microglia) and analyzed by qualitative and quantitative light microscopy.
The mean number of GFAP-immunoreactive astrocytes was significantly higher in untreated hydrocephalic animals compared to both types of controls (p < 0.001). Minocycline treatment of hydrocephalic animals reduced the number of GFAP immunoreactive cells significantly (p < 0.001). Likewise, the mean number of Iba-1 immunoreactive microglia was significantly higher in untreated hydrocephalic animals compared to both types of controls (p < 0.001). Furthermore, no differences in the numbers of GFAP-positive astrocytes or Iba-1-positive microglia were noted between control animals receiving no minocycline and control animals receiving minocycline, suggesting that minocycline does not produce an effect under non-injury conditions. Additionally, in six out of nine regions sampled, hydrocephalic animals that received minocycline injections had significantly thicker cortices when compared to their untreated hydrocephalic littermates.
Overall, these data suggest that minocycline treatment is effective in reducing the gliosis that accompanies hydrocephalus, and thus may provide an added benefit when used as a supplement to ventricular shunting.
Cerebrospinal Fluid Research 05/2010; 7(1):7. DOI:10.1186/1743-8454-7-7 · 1.81 Impact Factor
"Hydrocephalus occurs in approximately 20–40% of each litter, with obstruction of the aqueduct on day E18 [21,22]. The ventricular system dilates rapidly, as evidenced by an enlarged, domed dorsal cranium evident by 1–2 days of age . Most hydrocephalic rats die at 4–5 weeks of age if not treated by shunting procedures, which confer a normal life span [23,24]. "
[Show abstract][Hide abstract] ABSTRACT: There is mounting evidence that spinal fluid absorption takes place not only at the arachnoid villi, but also at several extracranial sites, which might serve as a reserve mechanism for, or be primarily involved in the absorption of CSF in hydrocephalus.
We compared the nasal lymphatic pathway in congenital Hydrocephalus-Texas (H-Tx) rats in unaffected and affected hydrocephalic (HC) siblings with that of control Sprague Dawley (SD) rat pups. The animals were examined after immediate post mortem injection of Evan's blue dye into the cisterna magna at 6 and 10 days of age. The specimens were evaluated for amount of dye penetration into the nasal passages.
We found more dye visualization in the olfactory regions of control SD (14/16 at P6, 14/16 at P10) and unaffected H-Tx (13/17 at P6, 13/16 at P10) compared with HC animals (0/14 at P6, 3/15 at P10). This difference was more pronounced at 10 days of age. The dye was not visualized in the cervical lymph nodes or venous channels in these acute experiments.
The results of this study suggest that nasal lymphatic cerebrospinal fluid absorption is reduced in the H-Tx rat hydrocephalus model.
Cerebrospinal Fluid Research 11/2008; 5(1):15. DOI:10.1186/1743-8454-5-15 · 1.81 Impact Factor
"Apart from human, congenital hydrocephalus has been reported to occur also in several strains of laboratory mammals (Bruni et al., 1988a). There are several animal models of congenital hydrocephalus involving spontaneous gene mutations (Raimondi et al., 1973; Kohn et al., 1981; Sasaki et al., 1983; Bruni et al., 1988b; Bronson and Lane, 1990; Pérez-Fígares et al., 1998), transgenic mutations (Dahme et al., 1997; Estivill-Torrú s et al., 2001; Davy and Robinson, 2003; Blackshear et al., 2003; Fernández-Llebrez et al., 2004), gene overexpression (Galbreath et al., 1995) or immunoneutralization of brain proteins (Vio et al., 2000). In several of these animals, aqueductal stenosis precedes and triggers hydrocephalus (Bruni et al., 1988a,b; Jones and Bucknall, 1988; Wagner et al., 2003). "
[Show abstract][Hide abstract] ABSTRACT: The hyh mouse carrying a point mutation in the gene encoding for soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein alpha (alpha-SNAP) develops inherited hydrocephalus. The investigation was designed to study: (i) the clinical evolution of hyh mice; (ii) factors other than the alpha-SNAP mutation that may influence the expression of hydrocephalus; (iii) the neuropathological features underlying the different forms of clinical evolution. The study included 3017 mice, 22.4% of which were hydrocephalic. The neuropathological study was performed in 112 mice by use of light and electron microscopy. It was found that maternal- and sex-related factors are involved in the heterogeneous expression of hyh phenotype. The clinical evolution recorded throughout a 4-year period also revealed a heterogeneous expression of the hydrocephalic phenotype. Two subpopulations were distinguished: (i) 70% of mice underwent a rapidly progressive hydrocephalus and died during the first 2 months of life; they presented macrocephaly, extremely large expansion of the ventricles, equilibrium impairment and decreased motor activity. (ii) Mice with slowly progressive hydrocephalus (30%) survived for periods ranging between 2 months and 2 years. They had no or moderate macrocephaly; moderate ventricular dilatation and preserved general motor activity; they all presented spontaneous ventriculostomies communicating the ventricles with the subarachnoid space, indicating that such communications play a key role in the long survival of these mice. The hyh mutant represents an ideal animal model to investigate how do the brain "adapt" to a virtually life-lasting hydrocephalus.
Neurobiology of Disease 08/2006; 23(1):152-68. DOI:10.1016/j.nbd.2006.02.009 · 5.08 Impact Factor
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