Elsevier

Neurobiology of Aging

Volume 19, Issue 5, September–October 1998, Pages 479-485
Neurobiology of Aging

Articles
Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging

https://doi.org/10.1016/S0197-4580(98)00081-5Get rights and content

Abstract

Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.

Section snippets

Subjects

MRI examination was performed on 18 beagle dogs from the animal facility at the Lovelace Respiratory Research Institute in Albuquerque, NM. The dogs consisted of 9 males and 9 females ranging in age from 4–15 years and weighing between 4 and 15 kg. All dogs had undergone cognitive testing during a 2-year period prior to the imaging study (14).

Cognitive testing

The test apparatus and cognitive tasks have been described in more detail elsewhere 14, 22. All cognitive testing took place in a modified Wisconsin

Results

Aged canines were impaired on a size-discrimination learning task but only a subset of old dogs performed poorly during object- approach learning and object-discrimination learning (14). Old dogs learned as well as younger dogs during reward approach learning, reversal learning and in the long-term retention test. The average test scores obtained from young (5 years and younger), middle aged (5–10 years) and old (10 years and older) dogs as a function of cognitive task are shown in Table 1.

Discussion

MRI was used to study changes in anatomical and vascular characteristics of the canine brain as a function of age. The quality of the anatomical images acquired by the 3D SPGR pulse sequence allowed us to clearly differentiate CSF from gray and white matter (Fig. 2). In old dogs, we observed pronounced ventricular enlargement and severe cortical atrophy, which is similar to age changes seen in humans. The size of the lateral ventricles increased slowly until the age of 10 years and progressed

Conclusion

We demonstrate that anatomical and vascular characteristics of canine brain can be simultaneously studied within a single MRI session. As in humans, ventricular enlargement was the most pronounced feature in aged dogs. The relationship between ventricle size and age was not linear, rather it was stable before age 10 and progressed very rapidly thereafter. The old dogs also exhibited deep gyri and widened sulci, indicating cortical atrophy. Vascular volume was not correlated with age however,

Acknowledgements

This work was supported in part by National Institute on Aging Grant No. AG05142 and D/AG12694–02S1 and a fellowship to M.-Y. Su from University of California at Irvine-Markey Program in Human Neurobiology. The authors thank Dr. Mary Berry and Marjorie A. Billau for their assistance in the animal study, and Benito Montoya for his assistance in image acquisition.

References (29)

  • L. Buee et al.

    Pathological alterations of the cerebral microvasculature in Alzheimer’s disease and related dementing disorders

    Acta Neuropathol. (Berl)

    (1994)
  • L. Buee et al.

    Brain microvascular changes in Alzheimer’s disease and other dementias

    Ann. N.Y. Acad. Sci.

    (1997)
  • P.C. Davis et al.

    The brain in older persons with and without dementia: Findings on MR, PET, and SPECT images

    Am. J. Roentgenol.

    (1994)
  • J. Davis–Salinas et al.

    Amyloid β-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells

    J. Neurochem.

    (1995)
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