A Novel Experimental Animal Model of Adult Chronic Hydrocephalus.

BACKGROUND: The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown. OBJECTIVE: To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus. METHODS: Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed. RESULTS: Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement. CONCLUSION: Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus. ABBREVIATION: NPH, normal pressure hydrocephalus.

Oral glucose loading modulates plasma ß-amyloid level in alzheimer's disease patients: potential diagnostic method for Alzheimer's disease.

BACKGROUND: Although plasma ß-amyloid (Aß) has been suggested to be a noninvasive diagnostic biomarker for Alzheimer's disease (AD), its significance and validity have been inconclusive. Thus, it is quite important to establish a novel diagnostic method related to plasma Aß. METHODS: As our previous animal studies demonstrated a relation of glucose with plasma Aß, we examined the effect of glucose loading on plasma Aß levels in AD patients. After fasting, an oral glucose load was administered to AD patients and non-AD dementia patients, and subsequently, blood glucose, plasma insulin, and plasma Aß levels were measured. RESULTS: The plasma levels of baseline blood glucose, plasma insulin, and plasma Aß were not different between the two groups. However, immediately after glucose loading, a significant increase in plasma Aß40 and Aß42 levels was observed in AD patients, whereas a mild decrease in plasma Aß40 and Aß42 levels was detected in non-AD dementia patients. CONCLUSION: The present study clearly demonstrated a different response in plasma Aß40 and Aß42 levels after glucose loading between AD and non-AD dementia patients, which is consistent with our previous animal studies. These findings suggest a novel diagnostic tool for AD using the elevation of plasma Aß level after glucose loading, although further studies are necessary.

Amyloid and Tau accumulate in the brains of aged hydrocephalic rats.

AD pathology is often seen in cortical biopsies of NPH patients. It remains unclear whether these findings are coincidental or causally related. In an aged animal model of NPH, we quantify Abeta and pTau accumulation and describe its temporal and spatial distribution. One-year-old male Sprague-Dawley rats had hydrocephalus induced by cisternal kaolin injection. Immunohistochemistry (IMHC) for AbetaPP, Abeta40, Abeta42 and pTau (epitope pT231) and ELISA for Abeta40, Abeta42 and pT231 were performed on controls and after 2, 6 and 10 weeks of hydrocephalus. Rats had double-label fluorescence IMHC for localization of Abeta42 and pT231. IMHC showed no change in neuronal AbetaPP expression following hydrocephalus. Abeta42 appeared earliest in CSF clearance pathways, p<0.05, and also showed significant rises in perivascular spaces and in cortical parenchyma. Mean ELISA values for Abeta40 and Abeta42 increased three- to four-fold in hydrocephalic rats at 6 and 10 weeks. Abeta40 increased between 2 and 6 weeks (p=0.0001), and remained stable at 10 (p=0.0002); whereas Abeta42 was elevated at 2 weeks (p<0.04) and remained at 6 (p=0.015). PTau at 6 and 10 weeks showed AD-like increased neuronal somatic staining and loss of dendritic staining. ELISA demonstrated increased pT231 in hydrocephalic rats at 10 weeks (p<0.0002). Double-label fluorescence for Abeta42 and pT231 revealed intraneuronal co-localization. Hydrocephalus in the elderly rat, therefore, can induce both Abeta and pTau accumulation. As distinct from brain injury models, no increase in AbetaPP expression was demonstrated. Rather, altered CSF dynamics appears to impair Abeta clearance in this NPH model.

[Unexpected drug-interaction].

The case of a male patient suffering from chronic normal pressure hydrocephalus is outlined. Antidepressant and pravastatin were administered because of the patient's abulia and hypercholesterolemia, but neuroleptic malignant syndrome-like conditions developed. All physicians should suppose the occurrence of such an "unexpected drug-interaction" in any case. The author considered that a good sense of careful discernment and rapid reference system of medical information are "essential tools" for clinical management.

[Normal pressure hydrocephalus--a rare late complication of radiography of the spine using contrast media]. / Normotenzní hydrocefalus--vzácná pozdní komplikace rentgen-kontrastního vysetrení pátere.

The aim of the study is to inform professionals about a serious complication--the liquor malabsorption--developing in relation to the routinely performed roentgen-contrastive examination (PMG). It also demonstrates advantages of the lumbal infusion test (LIT) as a part of the algorithm of the shunt operation in patients with supposed pathology of liquor malabsorption.

Sinusoidal intrathecal infusion for assessment of CSF dynamics in kaolin-induced hydrocephalus.

OBJECTIVE: To evaluate whether changes of CSF outflow resistance and compliance in hydrocephalus can be assessed by an intrathecal infusion which is performed at a sinusoidal varying rate. METHODS: Hydrocephalus was produced in 10 Sprague Dawley rats by instillation of 0.0375 g of kaolin in 0.9% saline into the cisterna magna. Measurements were performed 4 weeks later: With each animal both, three successive constant rate infusions (0-0.02 ml/min) and a sinusoidal infusion (0-0.02 ml/min, frequency 0.006 Hz) were performed. 6 normal animals served as control. The pressure recordings of both infusion techniques were used for the assessment of the CSF outflow resistance. The time constant and the pressure volume index were calculated only from the sinusoidal input testing. RESULTS: The sinusoidal test as well as the constant rate infusion both demonstrated a severe impairment of CSF absorption. By the sinusoidal input, a decreased compliance was confirmed additionally. Thus, the sinusoidal infusion test demonstrated a high resistance and low compliance hydrocephalus in the kaolin-treated group. A simple graphical procedure is presented which allows an easy assessment of CSF dynamics by the sinusoidal infusion test.