Biomedical subjects

Orin Bloch

Publications and source records attributed to Orin Bloch.

6 recordsLinked to original sources

PubMed2006

Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice.

Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain-CSF and blood-brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was approximately 5 mm Hg and ventricular size <0.3 mm(3) in control mice. Lateral ventricle volume increased to 3.7+/-0.5 and 5.1+/-0.5 mm(3) in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6+/-0.3 and 3.5+/-0.5 mm(3) in wildtype mice (P<0.005). The corresponding ICP was 22+/-2 mm Hg at 3 days in AQP4 null mice, significantly greater than 14+/-1 mm Hg in wildtype mice (P<0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to approximately 50 muL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multi-compartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.

Animals↗

PubMed2006

Three distinct roles of aquaporin-4 in brain function revealed by knockout mice.

Aquaporin-4 (AQP4) is expressed in astrocytes throughout the central nervous system, particularly at the blood-brain and brain-cerebrospinal fluid barriers. Phenotype analysis of transgenic mice lacking AQP4 has provided compelling evidence for involvement of AQP4 in cerebral water balance, astrocyte migration, and neural signal transduction. AQP4-null mice have reduced brain swelling and improved neurological outcome in models of (cellular) cytotoxic cerebral edema including water intoxication, focal cerebral ischemia, and bacterial meningitis. However, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema including cortical freeze-injury, brain tumor, brain abscess and hydrocephalus, probably due to impaired AQP4-dependent brain water clearance. AQP4 deficiency or knock-down slows astrocyte migration in response to a chemotactic stimulus in vitro, and AQP4 deletion impairs glial scar progression following injury in vivo. AQP4-null mice also manifest reduced sound- and light-evoked potentials, and increased threshold and prolonged duration of induced seizures. Impaired K+ reuptake by astrocytes in AQP4 deficiency may account for the neural signal transduction phenotype. Based on these findings, we propose modulation of AQP4 expression or function as a novel therapeutic strategy for a variety of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury.

Action Potentials↗

PubMed2006

Evaluation of registration techniques for spinal image guidance.

OBJECT: Paired point matching alone and paired point matching combined with surface matching are the two techniques used for the registration step in preoperative computerized tomography-based spinal image guidance. In the present study the authors sought to compare paired point-matching registration alone with paired point matching supplemented with surface matching to determine if the addition of surface matching improves navigational accuracy. METHODS: Pedicle screws were placed in three embalmed human cervicothoracic spinal specimens during image guidance to serve as a reference points. The specimens were then rescanned, and each level was registered using paired point matching alone and then by paired point supplemented with surface matching. Navigational accuracy was assessed by placing the stereotactic probe in the center of the screw head, and measuring the apparent distance between the screw head and probe on the computer monitor. Statistical analysis was used to compare the registration error and navigational error between the two techniques. Seventy-five screws were placed at 46 vertebral levels. The mean registration error for the paired point matching/surface matching technique (0.5 mm) was significantly lower (p < 0.001) than that of the paired point matching alone technique (1.2 mm); however, the intertechnique difference in navigational error was nearly equivalent (1.3 mm compared with 1.4 mm) and statistically insignificant (p > 0.05). CONCLUSIONS: Although the addition of surface matching to paired point registration significantly decreased the mean registration error, the actual navigational accuracy between the two techniques was equivalent when easily distinguishable points were meticulously selected. The use of paired point matching alone did not compromise the accuracy of navigation and is likely to result in decreased operating time.

Bone Screws↗

PubMed2005

K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator.

We synthesized a water-soluble, long-wavelength K(+) sensor, TAC-Red, consisting of triazacryptand coupled to 3,6-bis(dimethylamino)xanthylium, whose fluorescence increased 14-fold at 0-50 mM K(+) with K(+)-to-Na(+) selectivity >30. We visualized K(+) waves in TAC-Red-stained brain cortex in mice during spreading depression, with velocity 4.4 +/- 0.5 mm/min, and K(+) release and reuptake half-times (t(1/2)) of 12 +/- 2 and 32 +/- 4 s, respectively. Aquaporin-4 (AQP4) deletion slowed K(+) reuptake about twofold, suggesting AQP4-dependent K(+) uptake by astroglia.

Animals↗

PubMed2005

Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess.

Brain abscess is associated with local vasogenic edema, which leads to increased intracranial pressure and significant morbidity. Aquaporin-4 (AQP4) is a water channel expressed in astroglia at the blood-brain and brain-CSF barriers. To investigate the role of AQP4 in brain abscess-associated edema, live Staphylococcus aureus (10(5) colony-forming units) was injected into the striatum to create a focal abscess. Wild-type and AQP4-deficient mice had comparable immune responses as measured by brain abscess volume (approximately 3.7 mm3 at 3 days), bacterial count and cytokine levels in brain homogenates. Blood-brain barrier permeability was increased comparably in both groups as assessed by extravasation of Evans blue dye. However, at 3 days the AQP4 null mice had significantly higher intracranial pressure (mean +/- SEM 27 +/- 2 vs. 17 +/- 2 mmHg; p < 0.001) and brain water content (81.0 +/- 0.3 vs. 79.3 +/- 0.5 % water by weight in the abscess-containing hemisphere; p < 0.01) than wild-type mice. Reactive astrogliosis was found throughout the abscess-containing hemisphere; however, only a subset of astrocytes in the peri-abscess region of wild-type mice had increased AQP4 immunoreactivity. Our findings demonstrate a protective effect of AQP4 on brain swelling in bacterial abscess, suggesting that AQP4 induction may reduce vasogenic edema associated with cerebral infection.

Animals↗

PubMed2002

Color categories revealed by non-negative matrix factorization of Munsell color spectra.

Non-negative matrix factorization (NMF, Nature 401 (1999) 788-791) is a method to derive non-negative basis functions for sets of data that are inherently non-negative, such as color spectra. We applied NMF to Munsell color spectra and investigated the color names associated with the non-negative basis functions. NMF yields basis functions compatible with established color naming categories.

Color↗