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Enlargement of cerebral ventricles as an early indicator of encephalomyelitis.

Lepore S, Waiczies H, Hentschel J, Ji Y, Skodowski J, Pohlmann A, Millward JM, Paul F, Wuerfel J, Niendorf T, Waiczies S - PLoS ONE (2013)

Bottom Line: The increase in ventricle size was seen in the lateral, third and fourth ventricles.In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset.Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.

ABSTRACT
Inflammatory disorders of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis involve an invasion of immune cells that ultimately leads to white matter demyelination, neurodegeneration and development of neurological symptoms. A clinical diagnosis is often made when neurodegenerative processes are already ongoing. In an attempt to seek early indicators of disease, we studied the temporal and spatial distribution of brain modifications in experimental autoimmune encephalomyelitis (EAE). In a thorough magnetic resonance imaging study performed with EAE mice, we observed significant enlargement of the ventricles prior to disease clinical manifestation and an increase in free water content within the cerebrospinal fluid as demonstrated by changes in T2 relaxation times. The increase in ventricle size was seen in the lateral, third and fourth ventricles. In some EAE mice the ventricle size started returning to normal values during disease remission. In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset. Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.

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Time-line for weight, score and ventricle volume during EAE development.All the animals were weighed and scored before EAE induction and daily starting from the day of immunization onwards. At baseline and then starting from day 5 after EAE induction micro MRI measurements were performed and the ventricle volumes measured. Graph shows the temporal changes in weight (A), score (B) and ventricle volume (C) for control mice (n=6) and EAE mice (n=20) synchronized to the first day of clinical symptoms. (D) Weight, (E) score and (F) ventricle volume changes of EAE animals that showed remission in ventricle enlargement (n=3) against control animals (n=6).
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pone-0072841-g003: Time-line for weight, score and ventricle volume during EAE development.All the animals were weighed and scored before EAE induction and daily starting from the day of immunization onwards. At baseline and then starting from day 5 after EAE induction micro MRI measurements were performed and the ventricle volumes measured. Graph shows the temporal changes in weight (A), score (B) and ventricle volume (C) for control mice (n=6) and EAE mice (n=20) synchronized to the first day of clinical symptoms. (D) Weight, (E) score and (F) ventricle volume changes of EAE animals that showed remission in ventricle enlargement (n=3) against control animals (n=6).

Mentions: Next we compared the changes in ventricle volume with EAE signs and symptoms (weight and EAE score) during the progression of disease. Hence, for each mouse, we synchronized all 3 parameters (weight, clinical score and ventricle volume) to the day of first neurological symptoms, defined as time point 0 (Figure 3). The animal weight started decreasing 3-4 days before disease manifestation and started returning to normal 3-4 days after initiation of symptoms (Figure 3A). The average score at peak of disease severity was 1.9 ± 0.7 (± S.D.). The maximum was usually reached within the first 3 days following disease manifestation (Figure 3B).


Enlargement of cerebral ventricles as an early indicator of encephalomyelitis.

Lepore S, Waiczies H, Hentschel J, Ji Y, Skodowski J, Pohlmann A, Millward JM, Paul F, Wuerfel J, Niendorf T, Waiczies S - PLoS ONE (2013)

Time-line for weight, score and ventricle volume during EAE development.All the animals were weighed and scored before EAE induction and daily starting from the day of immunization onwards. At baseline and then starting from day 5 after EAE induction micro MRI measurements were performed and the ventricle volumes measured. Graph shows the temporal changes in weight (A), score (B) and ventricle volume (C) for control mice (n=6) and EAE mice (n=20) synchronized to the first day of clinical symptoms. (D) Weight, (E) score and (F) ventricle volume changes of EAE animals that showed remission in ventricle enlargement (n=3) against control animals (n=6).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750011&req=5

pone-0072841-g003: Time-line for weight, score and ventricle volume during EAE development.All the animals were weighed and scored before EAE induction and daily starting from the day of immunization onwards. At baseline and then starting from day 5 after EAE induction micro MRI measurements were performed and the ventricle volumes measured. Graph shows the temporal changes in weight (A), score (B) and ventricle volume (C) for control mice (n=6) and EAE mice (n=20) synchronized to the first day of clinical symptoms. (D) Weight, (E) score and (F) ventricle volume changes of EAE animals that showed remission in ventricle enlargement (n=3) against control animals (n=6).
Mentions: Next we compared the changes in ventricle volume with EAE signs and symptoms (weight and EAE score) during the progression of disease. Hence, for each mouse, we synchronized all 3 parameters (weight, clinical score and ventricle volume) to the day of first neurological symptoms, defined as time point 0 (Figure 3). The animal weight started decreasing 3-4 days before disease manifestation and started returning to normal 3-4 days after initiation of symptoms (Figure 3A). The average score at peak of disease severity was 1.9 ± 0.7 (± S.D.). The maximum was usually reached within the first 3 days following disease manifestation (Figure 3B).

Bottom Line: The increase in ventricle size was seen in the lateral, third and fourth ventricles.In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset.Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.

ABSTRACT
Inflammatory disorders of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis involve an invasion of immune cells that ultimately leads to white matter demyelination, neurodegeneration and development of neurological symptoms. A clinical diagnosis is often made when neurodegenerative processes are already ongoing. In an attempt to seek early indicators of disease, we studied the temporal and spatial distribution of brain modifications in experimental autoimmune encephalomyelitis (EAE). In a thorough magnetic resonance imaging study performed with EAE mice, we observed significant enlargement of the ventricles prior to disease clinical manifestation and an increase in free water content within the cerebrospinal fluid as demonstrated by changes in T2 relaxation times. The increase in ventricle size was seen in the lateral, third and fourth ventricles. In some EAE mice the ventricle size started returning to normal values during disease remission. In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset. Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.

Show MeSH
Related in: MedlinePlus