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Cocaine-induced cortical microischemia in the rodent brain: clinical implications

Molecular Psychiatry volume 17, pages 1017–1025 (2012)Cite this article

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Abstract

Cocaine-induced stroke is among the most serious medical complications associated with its abuse. However, the extent to which acute cocaine may induce silent microischemia predisposing the cerebral tissue to neurotoxicity has not been investigated; in part, because of limitations of current neuroimaging tools, that is, lack of high spatiotemporal resolution and sensitivity to simultaneously measure cerebral blood flow (CBF) in vessels of different calibers (including capillaries) quantitatively and over a large field of view. Here we combine ultrahigh-resolution optical coherence tomography to enable tracker-free three-dimensional (3D) microvascular angiography and a new phase-intensity-mapping algorithm to enhance the sensitivity of 3D optical Doppler tomography for simultaneous capillary CBF quantization. We apply the technique to study the responses of cerebral microvascular networks to single and repeated cocaine administration in the mouse somatosensory cortex. We show that within 2–3 min after cocaine administration CBF markedly decreased (for example, ∼70%), but the magnitude and recovery differed for the various types of vessels; arterioles had the fastest recovery (∼5 min), capillaries varied drastically (from 4–20 min) and venules showed relatively slower recovery (∼12 min). More importantly, we showed that cocaine interrupted CBF in some arteriolar branches for over 45 min and this effect was exacerbated with repeated cocaine administration. These results provide evidence that cocaine doses within the range administered by drug abusers induces cerebral microischemia and that these effects are exacerbated with repeated use. Thus, cocaine-induced microischemia is likely to be a contributor to its neurotoxic effects.

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Acknowledgements

This work was supported in part by the National Institutes of Health Grants K25-DA021200 (CD), 2R01-DK059265 (YP), 1RC1DA028534 (CD and YP), 1R21-DA032228 (CD and YP) and NIAAA Intramural Research Program (NDV).

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Authors and Affiliations

  1. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA

    H Ren, C Du, Z Yuan, K Park & Y Pan

  2. Medical Department, Brookhaven National Laboratory, Upton, NY, USA

    C Du

  3. National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA

    N D Volkow

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  1. H Ren
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  2. C Du
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  5. N D Volkow
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Correspondence to C Du or Y Pan.

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Ren, H., Du, C., Yuan, Z. et al. Cocaine-induced cortical microischemia in the rodent brain: clinical implications. Mol Psychiatry 17, 1017–1025 (2012). https://doi.org/10.1038/mp.2011.160

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